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

Not Applicable

Completed

• Conditions: Neonatal Sepsis
• Interventions: Drug: Piperacillin-Tazobactam and Amikacin

• Registration Number: NCT01290003
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2010-06
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Study First Submitted: 2011-02-03
• Study First Submitted QC: 2011-02-03
• Study First Posted: 2011-02-04
• Status Verified: 2015-09
• Last Update Submitted: 2015-09-26
• Last Update Posted: 2015-09-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

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

Exclusion Criteria

• Major Congenital malformation
• Refusal of consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Antibiotic Group	Piperacillin-Tazobactam and Amikacin	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.

Primary Outcome Measures

Name	Time	Method
Incidence of sepsis	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/cu.mm.(Low 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

Name	Time	Method
Mortality;	First 28 days of life
Respiratory support;	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
Duration of Hospital stay	Till discharge
Complications	Till discharge	Incidence of PPHN by Echocardiography, Pneumothorax by transillumination confirmed by chest x-ray, azotemia by Kidney function test panel

Trial Locations

Locations (1)

Kalawati Saran children's Hospital, Lady Hardinge Medical College; 🇮🇳 New Delhi, Delhi, India