Research question

Does intravenous immunoglobulin infusion in neonates affect blood flow in their superior mesenteric artery and celiac artery?

Aims

• To study the changes in SMA and celiac artery Doppler indices in neonates receiving immunoglobulin therapy
• To study the incidence of NEC/ feed intolerance in neonates receiving IVIg and correlate the Doppler flow changes with the clinical presentation

Inclusion criteria

Neonate receiving intravenous immunoglobulin, irrespective of their gestation and birth weight

Exclusion criteria

• Neonates with established NEC or surgical abdomen like malrotation prior to starting IVIg
• Neonates developing complications of immunoglobulin therapy like hypotension or anaphylaxis

Materials and methods

Setting: Neonatal unit, Dept of Pediatrics, PGIMER, Chandigarh

Type of study: Prospective study

            All neonates with Rh isoimmunization or neonatal alloimmune thrombocytopenia who are eligible for immunoglobulin therapy will be prospectively enrolled irrespective of their gestation and birth weight after obtaining informed consent from parents. Baseline clinical characteristics including feeding pattern and abdominal examination findings will be documented. A baseline SMA and celiac artery Doppler will be done prior to starting immunoglobulin infusion and this will be done pre-feed if baby is on feeds. Doppler indices (Peak systolic velocity, end diastolic velocity, time average mean velocity, pulsatility index, resistance index, S/D ratio) will be measured using PHILIPS ATL 1500 USG machine of our unit. Both the blood vessels will be sampled close to their origin from abdominal aorta by keeping the Doppler probe in the epigastrium. Immunoglobulin will be administered intravenously at a dose of 0.5-1g/kg as an infusion over 2 hours as per the protocol in our unit.¹ Babies will be kept nil per oral during these 2 hours. Doppler will be done again after its completion. Repeat dose of IVIg may be given after 12 hours of the first dose based on the clinical condition of the baby.  Babies will be followed up till 5 days after IVIg infusion for the development of feed intolerance or NEC, which are defined below. Ethical approval will be obtained from the Institutes ethics committee.

Feed intolerance is defined if following symptoms are present for which feeds have to be withheld for 12 hours or more

• Gastric residual >50% of the feed volume
• Increase in abdominal girth by ≥ 2cm in 6 hours
• Bilious/bloody/coffee ground aspirates
• Multiple episodes of vomiting²

NEC is defined as per modified Bell’s staging.³

Primary outcome

Change in SMA/Celiac Doppler indices after immunoglobulin therapy

Secondary outcome

Incidence of NEC and feed intolerance (within 5 days of the IVIg infusion)

Statistical analysis

For baseline variables, descriptive statistics will be used. For comparing pre- and post immunoglobulin Doppler indices, RM-ANOVA will be used. McNemar test will be used to compare categorical variables before and after therapy. P value <0.05 is considered significant.

Bibliography

1.         Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114: 297-316.

2.         Enteral nutrition. In: Kumar P DS, editor. PGI NICU Handbook of protocols. 4th ed. Chandigarh: The New Heart Trust; 2010. p. 68-82.

3.         Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187: 1-7.