LONDON - Even if they have been told about it beforehand, most new parents are taken aback when they see the contents of their baby's first dirty nappy.

The baby's first stools, known as meconium, are sticky and almost black, resembling tar or treacle.

Most babies pass the first meconium after delivery, but in a small percentage of cases they pass meconium while still in the uterus, with the risk that the substance may enter their lungs. Meconium aspiration syndrome may result, which can be fatal.

Now a group of researchers in the Netherlands has shown that interleukin-8 (IL-8) is present in meconium and that this cytokine can attract neutrophils. They suggest this mechanism may account for the inflammation of the lungs that occurs in meconium aspiration syndrome.

Arnout Jan de Beaufort, neonatologist in the department of pediatrics at the Leiden University Medical Centre, told BioWorld International, “Although it is a long way off, one could speculate this finding could one day help in the development of anti-inflammatory therapies to treat meconium aspiration syndrome, perhaps involving the delivery of anti-IL-8 to the lungs.“

In one in 10 deliveries, the amniotic fluid that surrounds the infant in the uterus becomes stained with meconium. The usual cause for this is fetal distress resulting from a reduced supply of oxygen reaching the fetus, perhaps because the placenta is no longer functioning efficiently or because the umbilical cord has become compressed during birth.

Obstruction, Inflammation Characterize Disorder

Depending on the study, between 5 and 30 percent of babies who pass meconium while in the uterus go on to develop meconium aspiration syndrome. Two factors play an important role in its development.

First, there may be complete or partial obstruction of the lower airways by the solid matter of the meconium, so that the affected part of the lung is not ventilated properly. If there is partial obstruction, air may be sucked in but may not be expelled, resulting in a phenomenon called air trapping. A pneumothorax (air in pleural cavity, the space between the lungs and the rib cage) may develop. In either case, the infant's uptake of oxygen and excretion of carbon dioxide is likely to be impaired.

Second, the meconium causes a chemical pneumonitis: inflammation of the lungs and airways. It also has been shown that meconium can hydrolyze surfactant, which is necessary to coat the internal walls of the alveoli (air sacs) of the lungs to allow them to inflate following birth. The result is a baby who is blue, has low blood oxygen levels and is in serious respiratory distress.

Meconium aspiration syndrome is treated by ventilation and with oxygen, but it can be fatal. In various studies summarizing several series of patients, mortality rates for those with meconium aspiration syndrome varied from 5 to 37 percent, with the median at 12 percent.

De Beaufort and his colleagues decided to investigate what was causing the inflammation of the lungs in meconium aspiration syndrome. He said, “We knew that there were many neutrophils in the lung, but we wanted to know how they got there. So we decided to see whether meconium itself exerted a chemotactic effect on neutrophils.“

The team collected the first meconium passed from the nappies of eight newborn babies. Seven of these samples were sterile and used in the study; the eighth was contaminated with bacteria and discarded.

The researchers also obtained neutrophils from the cord blood of newborn infants. They then carried out experiments to determine whether the presence of meconium could stimulate chemotaxis of the neutrophils.

As reported in the Lancet, July 11, 1998, in a paper titled “Effect of interleukin 8 in meconium on in vitro neutrophil chemotaxis,“ they found that when the scores for the seven samples were averaged, neutrophil migration induced by meconium was significantly greater than random migration (p = 0.004).

De Beaufort said, “We then had to decide which chemotactic agent was responsible for the reaction, and we decided that IL-8 was a likely candidate because it plays an important role in attracting neutrophils to sites of inflammation.“

Having confirmed that IL-8 was indeed present in all seven samples, he and his colleagues found they could block the increased migration of neutrophils by adding a monoclonal antibody to IL-8.

“We were not able to show a clear relationship between the concentration of IL-8 and the chemotactic effect,“ de Beaufort added. “All samples showed a chemotactic effect, but the concentrations of IL-8 in them were quite different. This may be because IL-8 is present, but bound or inactivated in some way.“

No one knows where the IL-8 in meconium comes from or why it is there. De Beaufort said many cytokines are present in the amniotic fluid at the end of pregnancy, and IL-8 is just one of them. “The infant could swallow IL-8 in the amniotic fluid and it could enter the gut that way, or it may be that it comes directly from the infant's gut, because there are many things in the gut that contribute to the meconium, including various cells and cellular products.“

It is too early to say what the clinical implications of this finding might be, de Beaufort said, although it is possible to speculate it may help in developing anti-inflammatory therapies to treat meconium aspiration syndrome.

Although the group has shown the chemotactic effect of meconium is present in vitro, he added, it has not shown that meconium aspirated by the infant will cause an inflammatory reaction due to the IL-8 in it.

Next the team plans to develop an animal model for meconium aspiration syndrome and investigate whether meconium enhances the inflammatory reaction in the lungs. The researchers also will try to find out what other factors present in meconium contribute to the inflammatory reaction. *