Missing Microbes in Infants Born by Cesarean Section

NCT04134819 | Unknown

• 1 other identifier: APC088
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

General adult healthy pregnant females in total 400, as well as their infants will be recruited. It is expected 67% will be vaginally delivered and 33% will be C Section deliveries. It is expected that of these groups that 40% of these women will be treated with antibiotics during their pregnancy. All C Section women (including emergency C Section) will be treated with IV Cefazolin at the time of incision, in theatre, to prevent internal wound infection. Primary objective The effect of maternal antibiotic administration during pregnancy upon the development of the intestinal microbiota until the age of two years; of C-section delivered infants compared to C-section delivered infants born to non-antibiotic treated pregnant women. To develop a cohort of vaginally delivered infants to isolate the 'missing microbes' (intestinal) in the groups above. Secondary objective The effect of maternal antibiotics on the developing infant by:

• Anthropometric assessment: Body weight and Body length
• Bayley scale of infant development test at age 2 years Ancillary
• To isolate and characterise bacterial strains from fresh healthy infant faeces that are altered in the stools from C-section delivered and antibiotic treated infants and compared to vaginally delivered infants.
• The effect of maternal antibiotic treatment on the human milk microbiome during lactation
• Stress hormone levels of mothers and infants
• Mental health questionnaire of mothers
• Food frequency questionnaire of mothers Exploratory
• To identify bacterial strains that can be further developed into probiotic products to help replenish depleted microbiota in the infant gut, born by C Section and or treated with antibiotics

Conditions

C Section

Outcome Measures

Primary Outcomes (1)

• Differences in intestinal microbiota between C-section delivered infants exposed to maternal antibiotic administration during pregnancy and non-exposed infants

  The effect of maternal antibiotic administration during pregnancy upon the development of the intestinal microbiota until the age of two years; of C-section delivered infants compared to C-section delivered infants born to non-antibiotic treated pregnant women. To develop a cohort of vaginally delivered infants to isolate the 'missing microbes' (intestinal) in the groups above.

  2 years

Secondary Outcomes (3)

• The effect of maternal antibiotics on the developing infant by:

  24 weeks and 12 months

• The effect of maternal antibiotics on the developing infant by:

  24 weeks and 12 months

• The effect of maternal antibiotics on the developing infant by:

  24 weeks and 12 months

Other Outcomes (5)

• To isolate and characterise bacterial strains from fresh healthy infant faeces

  birth, one week post birth, 4 weeks, 8 weeks, 24 weeks, 12 months, 18 months and 24 months.

• The effect of maternal antibiotic treatment on the human milk microbiome during lactation

  1, 4, 8 weeks, 6 months and 12 months

• Stress hormone levels of mothers and infants

  4 weeks

Study Arms (4)

Vaginally Delivered Babies- No antibiotic treatment

Adult healthy pregnant females (in total 400) as well as their infants will be recruited. It is expected 67% of babies will be vaginally delivered and that 60% will not have antibiotic treatment during pregnancy. This will be up to 161 mother/infant dyads.

Vaginally Delivered Babies- antibiotic treatment

It is expected based from previous hospital statistics that 67% of babies will be vaginally delivered and 40% of these women will be treated with antibiotics during pregnancy. This could be up to 107 mother/infant dyads.

C-section Delivered Babies- No antibiotic treatment

It is expected based from previous hospital statistics that 33% of babies will be delivered by C section and that 60% will not have antibiotic treatment during pregnancy. This will be up to 80 mother/infant dyads All C Section women (including emergency C Section) will be treated with IV Cefazolin at the time of incision, in theatre, to prevent internal wound infection.

C-section Delivered Babies- antibiotic treatment

It is expected based from previous hospital statistics that 33% of babies will be delivered by c section and 40% of these women will be treated with antibiotics during pregnancy. This could be up to 52 mother/infant dyads .All C Section women (including emergency C Section) will be treated with IV Cefazolin at the time of incision, in theatre, to prevent internal wound infection.

Eligibility Criteria

• Age: 22 Years - 40 Years
• Gender Eligibility Details: Pregnant Mothers are recruited to the study based on gender Gender is not a criteria for Infants
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pregnant women will be approached during the 3rd trimester at antenatal clinics. An arrangement will be made to meet them at their next hospital visit to obtain consent and stool sample. An information leaflet about the study will be given \& the aim of the study will also be explained to them by the research nurse/researcher. They will be given time to make an informed decision \& to ask questions regarding the study; if they wish to participate with their infant, the putatively eligible participants must sign the informed consent form (ICF) before beginning any study-related activities. Hereafter an inclusion/exclusion checklist will be completed. Participants will complete a food frequency questionnaire and mental health questionnaire during the screening visit as well as during visit 6.

You may qualify if:

• Pregnant females of age 22 to 40 years
• Singleton pregnancy
• Infants born within the Cork University Maternity Hospital
• Women who are intending to exclusively breast feed their infant for a minimum of 6 weeks
• Mothers who give birth to full term infants greater than 35 weeks' gestation
• Infants who are born healthy with no underlying illness, syndrome or chronic disease
• Participants who agree to maintain their usual dietary habits throughout the trial period
• Ability of the participant (in the investigator's opinion) to comprehend the full nature and purpose of the study including possible risks and side effects
• Consent to participate in the study and willing to comply with the protocol and study restrictions.

You may not qualify if:

• Sick infants who are admitted to the neonatal unit
• Stillbirth or live birth where the baby is born alive but dies shortly after.
• Infants born less than 35 (34 weeks +6 days) weeks gestation
• Infants who are formula fed exclusively before 6 weeks of age
• Mothers with insulin dependent gestational diabetes)
• Mothers and infants who will live more than 45 minutes (driving) from hospital on discharge.
• Self-declare history of alcohol abuse (for females: \>3 drinks on any single day and \>7 drinks per week
• Self-declare use of illicit drugs
• Participants under administrative or legal supervision.
• Participation in another study with any investigational product within 60 days of screening

Sponsors & Collaborators

• University College Cork: lead
• Dupont Applied Biosciences: collaborator

Study Sites (1)

Cork University Maternity Hospital, APC Microbiome Ireland, University College Cork, and Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork. IRELAND

Cork, Munster, Ireland

RECRUITING

Related Publications (1)

• Warda AK, Dempsey EM, Forssten SD, Ryan CA, Cryan JF, Patterson E, O'Riordan MN, O'Shea CA, Keohane F, Meehan G, O'Connor O, Ross RP, Stanton C. Cross-sectional observational study protocol: missing microbes in infants born by caesarean section (MiMIC): antenatal antibiotics and mode of delivery. BMJ Open. 2022 Nov 2;12(11):e064398. doi: 10.1136/bmjopen-2022-064398.

  PMID: 36323464 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Samples with microbial DNA not human DNA. The following samples will be collected: Faecal (adult), faecal (infant), urine (infant), saliva cortisol (adult and infant), hair (adult and infant), breast milk, vaginal swab or skin swab.

Study Officials

• Eugenen M Dempsey, PhD MD

  APC Microbiome Ireland, University College Cork, Ireland.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eugene M Dempsey, PhD MD

CONTACT

+ 353 21 492 0524; G.Dempsey@ucc.ie

Susan M Rafferty-McArdle, PhD

CONTACT

+ 353 21 490 1753; s.rafferty@ucc.ie

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Neonatologist

Study Record Dates

• First Submitted: October 18, 2019
• First Posted: October 22, 2019
• Study Start: July 1, 2019
• Primary Completion: July 30, 2023
• Study Completion: May 30, 2025
• Last Updated: January 9, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)