Role of Antibiotics in Preventing Infection in Babies Born Through Meconium Stained Liquor (AbProM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01290003
Recruitment Status : Completed
First Posted : February 4, 2011
Last Update Posted : September 29, 2015
Information provided by (Responsible Party):
Sushma Nangia, M.D., Lady Hardinge Medical College

Brief Summary:
The purpose of the study is to evaluate the role of antibiotics in preventing infection in babies born through meconium stained amniotic fluid. Normally babies do not pass meconium while in utero. In response to hypoxic stress babies may pass meconium before birth and are likely to be candidates for problems related to meconium passage and its inhalation. It is believed that these babies are more prone to infections as meconium enhances bacterial growth and may predispose such babies to secondary bacterial infections. In addition, meconium passage has been incriminated as a pointer of in-utero infection. Whether use of antibiotics in babies born through meconium stained amniotic fluid will reduce the infectious episodes and complications thereof or not is not clear. Moreover, there is not much published literature to prove or refute the same. Most clinicians have a low threshold for using antibiotics in such babies. In view of the uncertainty regarding antibiotic usage in these babies, the investigators decided to investigate the role of prophylactic antibiotics in prevention of neonatal sepsis in babies born through meconium stained amniotic fluid.

Condition or disease Intervention/treatment Phase
Neonatal Sepsis Drug: Piperacillin-Tazobactam and Amikacin Not Applicable

Detailed Description:

Meconium passage in newborn infants is a developmentally programmed event normally occurring within first 24-48 hours of birth. Intra uterine meconium passage in near term or term fetuses has been associated with feto-maternal stress factors and/or infections, whereas meconium passage in post term pregnancies has been attributed to gastro-intestinal maturity. The meconium staining of amniotic fluid occurs in 12% of all live births per annuum. Aspiration of meconium that occurs during intra uterine life or after delivery with the first few breaths may result in or contribute to respiratory pathology known as meconium aspiration syndrome (MAS) which represents a leading cause of the perinatal morbidity, occurring in 5-20% of all babies born through MSAF.

The routine use of antibiotics in MSAF babies has been advocated for a long time as a part of the conventional treatment. Meconium passage in utero is hypothesized to represent a response to fetal bacterial infection in addition to intrauterine hypoxia. Additionally the rationale for use of antibiotics includes the radiographic similarity of MAS to bacterial pneumonia, in vitro enhancement of bacterial growth in presence of meconium as well as the possibility of meconium induced inhibition of phagocytic activity and respiratory burst response by alveolar macrophages rendering patients with MAS more susceptible to infection. These recommendations however are empirical and the incidence of bacterial infection in neonates born through MSAF as well as in MAS has not been systematically evaluated, to date. With the rising concern about the emergence of resistant strains in neonatal ICUs and the possible side effects of antibiotics (like amino glycosides) including nephrotoxicity and ototoxicity in neonates, a systematically conducted, randomized controlled trial is necessary to assess the utility of antibiotics in the routine management of infants with MSAF and MAS. Hence the purpose of this prospective randomized controlled trial is to compare the clinical course, complications, and infection related outcomes in cases of MSAF and MAS, treated with or without antibiotics therapy

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Role of Prophylactic Antibiotics in Preventing Neonatal Sepsis in Neonates Born Through Meconium Stained Amniotic Fluid - A Randomized Controlled Trial
Study Start Date : June 2010
Actual Primary Completion Date : January 2011
Actual Study Completion Date : January 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics Sepsis
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Antibiotic Group
Neonates randomized to intervention Group(Antibiotic group)will receive the first line antibiotics (Piperacillin-Tazobactam and Amikacin) as per the unit policy for 72 hours. These neonates will also be monitored by performing sepsis screens and blood culture for development of sepsis.
Drug: Piperacillin-Tazobactam and Amikacin
Inj Piperacillin-Tazobactam 50 mg/Kg/dose 12 hourly IV X 3 days (6 doses) Inj Amikacin 15 mg/kg/dose 24 hourly IV X 3 days (3 doses)
No Intervention: No Antibiotic Group
Neonates randomized to 'No antibiotic group' will receive supportive treatment as per standard unit protocol. These neonates will be monitored by performing sepsis screens and blood culture for development of sepsis.

Primary Outcome Measures :
  1. Incidence of sepsis [ Time Frame: First 28 days of life ]

    Incidence of sepsis in first 28 days defined as -

    1. SUSPECTED SEPSIS - Sepsis Screen > 2 parameters positive and/or
    2. CONFIRMED SEPSIS - Sepsis Screen positive + Blood or CSF culture positive for bacteria.

    Sepsis Screen

    1. Total leukocyte count < 5000/mm3
    2. Absolute neutrophil count < 1800/ counts as per Monroe chart for term neonates)
    3. Immature/total neutrophil ratio > 0.2
    4. Micro-ESR > 15mm in 1st hour
    5. C Reactive Protein (CRP) > 1 mg/dl

Secondary Outcome Measures :
  1. Mortality; [ Time Frame: First 28 days of life ]
  2. Respiratory support; [ Time Frame: Till discharge from the hospital ]
    1. Requirement of respiratory support
    2. The mode of respiratory support viz. Supplemetal Oxygen therapy, CPAP, Mechanical ventilation, High Frequency ventilation
    3. Duration of each kind of respiratory support required

  3. Duration of Hospital stay [ Time Frame: Till discharge ]
  4. Complications [ Time Frame: Till discharge ]
    Incidence of PPHN by Echocardiography, Pneumothorax by transillumination confirmed by chest x-ray, azotemia by Kidney function test panel

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 2 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Gestation > 37 weeks
  • Meconium staining of amniotic fluid
  • Cephalic presentation
  • Singleton pregnancy

Exclusion Criteria:

  • Major Congenital malformation
  • Refusal of consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01290003

Kalawati Saran children's Hospital, Lady Hardinge Medical College
New Delhi, Delhi, India, 110001
Sponsors and Collaborators
Lady Hardinge Medical College
Study Chair: Sushma Nangia, MBBS, MD, DM Lady Hardinge Medical College, New Delhi, India

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Sushma Nangia, M.D., Professor Pediatrics, Lady Hardinge Medical College Identifier: NCT01290003     History of Changes
Other Study ID Numbers: LHMC/054/Ab-Pro-M
First Posted: February 4, 2011    Key Record Dates
Last Update Posted: September 29, 2015
Last Verified: September 2015

Keywords provided by Sushma Nangia, M.D., Lady Hardinge Medical College:
Antibacterial agents
Meconium stained amniotic fluid
Neonatal sepsis

Additional relevant MeSH terms:
Neonatal Sepsis
Systemic Inflammatory Response Syndrome
Pathologic Processes
Infant, Newborn, Diseases
Anti-Bacterial Agents
Piperacillin, tazobactam drug combination
Penicillanic Acid
Antibiotics, Antitubercular
Anti-Infective Agents
Antitubercular Agents
beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action