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

Role of Prophylactic Antibiotics in Preventing Neonatal Sepsis in Neonates Born Through Meconium Stained Amniotic Fluid - A Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Neonatal Sepsis
• Intervention / Treatment: Drug: Piperacillin-Tazobactam and Amikacin

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
• Enrollment (Actual): 250
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110001
      • Kalawati Saran children's Hospital, Lady Hardinge Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

• Major Congenital malformation
• Refusal of consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of sepsis	Incidence of sepsis in first 28 days defined as -; SUSPECTED SEPSIS - Sepsis Screen > 2 parameters positive and/or; CONFIRMED SEPSIS - Sepsis Screen positive + Blood or CSF culture positive for bacteria. Sepsis Screen; Total leukocyte count < 5000/mm3; Absolute neutrophil count < 1800/cu.mm.(Low counts as per Monroe chart for term neonates); Immature/total neutrophil ratio > 0.2; Micro-ESR > 15mm in 1st hour; C Reactive Protein (CRP) > 1 mg/dl	First 28 days of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality;		First 28 days of life
Respiratory support;	Requirement of respiratory support; The mode of respiratory support viz. Supplemetal Oxygen therapy, CPAP, Mechanical ventilation, High Frequency ventilation; Duration of each kind of respiratory support required	Till discharge from the hospital
Duration of Hospital stay		Till discharge
Complications	Incidence of PPHN by Echocardiography, Pneumothorax by transillumination confirmed by chest x-ray, azotemia by Kidney function test panel	Till discharge

Collaborators and Investigators

• Sponsor: Lady Hardinge Medical College
• Investigators: Study Chair: Sushma Nangia, MBBS, MD, DM, Lady Hardinge Medical College, New Delhi, India

Publications and helpful links

General Publications

• Goel A, Nangia S, Saili A, Garg A, Sharma S, Randhawa VS. Role of prophylactic antibiotics in neonates born through meconium-stained amniotic fluid (MSAF)--a randomized controlled trial. Eur J Pediatr. 2015 Feb;174(2):237-43. doi: 10.1007/s00431-014-2385-4. Epub 2014 Aug 3.

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: February 3, 2011
• First Submitted That Met QC Criteria: February 3, 2011
• First Posted (Estimate): February 4, 2011

Study Record Updates

• Last Update Posted (Estimate): September 29, 2015
• Last Update Submitted That Met QC Criteria: September 26, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Neonate; Neonatal sepsis; Meconium stained amniotic fluid; Antibacterial agents
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Sepsis; Neonatal Sepsis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amikacin; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination
• Other Study ID Numbers: LHMC/054/Ab-Pro-M