Neonatology: 50 years to get from none to... nearly all

Whereas a very premature infant had almost no chance of survival 50 years ago, s/he can expect to live and develop normally today. A lacuna that the physician-researchers at Inserm have helped to fill. Prof Pierre‑Henri Jarreau, head of the Port-Royal (Neonatal Medical and Resuscitation Service (Cochin Hospital, Paris) retraces the history.

In the 1950s, management of premature infants could have been described as non-existent, and 85% of infants weighing less than 1.5 kg at birth died. Today, 85% of these infants leave hospital alive, usually without sequelae. In other words, extraordinary progress has been made in the last half-century, fifty years that have marked the advent of medicine for the newborn, or “neonatology.”

Resuscitation and respiratory support

Premature infant © Inserm, M. Depardieu

Premature infant

The big leap forward for these infants begins in the early 1960s, with the development of techniques for resuscitation and respiratory support enabling newborns with life-threatening conditions to be saved. In France, paediatric resuscitation is pioneered by Gilbert Huault, who successfully adapts the techniques used for adult resuscitation to infants. Prolonged intubation with modified tracheal tubes, control of blood gases and assisted ventilation save lives.

In the 1980s, the benefit of administering corticosteroids to the mother antenatally in cases of threatened premature delivery is demonstrated. It will become a standard treatment in the middle of the following decade. This treatment accelerates lung maturation in the unborn child, and reduces mortality and neurological complications, especially the risk of intracranial (intraventricular) haemorrhage. From the beginning for the 1990s, exogenous surfactants (developed in the 1980s) are administered after birth in order to compensate for the immaturity of the lungs in premature infants.

With respect to nutrition, knowledge relating to the requirements of premature infants has also advanced. This knowledge helped to make available intravenous solutions and milks that are tailored to meet the specific needs of these infants and their brain development.

Finally, the establishment of a new system of care organisation, with the help of perinatal epidemiology data, considerably improved the prognosis for these infants: the classification of maternity units into three categories enables women at risk of an excessively early delivery to give birth in Type 3 centres, which are fully equipped for optimal and immediate management of very premature infants.

Inserm, a major player in these advances

Alexandre Minkowski - © Inserm, M. Depardieu

Alexandre Minkowski

“This impressive progress is the fruit of the energy and conviction of a few individuals, including several Inserm researchers. They were able to demonstrate the specific physiological and pathophysiological features of neonates, especially premature neonates, enabling an improvement in the medical approach,” explains Pierre‑Henri Jarreau. Alexandre Minkowski was a pioneer in the field in the 1950s. He introduced neonatology from the United States. He organised the first neonatal care centre at the Baudelocque obstetric clinic in Paris, followed by the first neonatal intensive care unit at Port-Royal. Very quickly, other large neonatal centres emerged, headed by Bernard Salle in Lyon, Paul Vert in Nancy and Pierre Lequien in Lille.

“Alexandre Minkowski’s clinical activity was soon combined with research, with the creation of the ‘Biology of Foetal and Neonatal Development’ laboratory which would become Inserm Unit 29 in 1964.Research at the laboratory helped to provide a better understanding of the pathologies seen in premature infants. This step marked the beginnings of the study of neonatology and prematurity in France,” the researcher outlines. Other laboratories then came into being, and the publications multiplied. The research dealt with brain development, an area in which France continues to excel through the work of Pierre Gressens’ team, or lung development, with Jacques Bourbon’s work on the surfactant, for example.

Apart from neonatology, attention also focused on perinatology, combining obstetrics and paediatrics. Thus the mechanisms associated with premature birth and its risk factors were studied by Emile Papiernik and other researchers devoted to epidemiology. Claude Rumeau-Rouquette, for example, carried out the first studies of perinatal epidemiology in France. She would establish Unit 149, devoted to maternal and child health epidemiology.

 

Neurological sequelae, a challenge for tomorrow

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In 2014, the balance sheet is unequivocal. Over 85% of moderate or late premature infants (born between 32 and 36 weeks of amenorrhoea), and very premature infants (born between 28 and 32 weeks) weighing over 1.5 kg at birth survive. Premature infants with a lower gestational age, born between 24 and 27 weeks of amenorrhoea and weighing less than a kilogram, also survive in 70% of cases (50% at 25 weeks of amenorrhoea, 75% at 26 weeks), sometimes at the cost of sequelae, which represent an ethical problem in relation to the infant, his/her family and society. “There has been considerable progress in the management of respiratory distress. Neurological complications, which have become the primary cause of death for very premature infants in many care units, are still the big challenge. Furthermore, despite important advances in neuroimaging and neurosciences, the neurological and developmental prognosis for very premature infants still remains uncertain,” according to Pierre-Henri Jarreau. Indeed, research is now turning to the outlook for these infants, who might not have lived 50 years ago. The team at Inserm Unit 953 (which succeeded Unit 149), will thus monitor the development of children born very prematurely in 2011 to the age of 12 years (Epipage2 Cohort). It thus hopes to obtain valuable information on the efficacy of care or on risk factors for sequelae associated with premature birth.

 

Further information 
See our information pack on premature birth 
Read the biographies of Pierre Gressens, Alexandre Minkowski, Emile Papiernik and Claude Rumeau-Rouquette on the Histoire de l’Inserm (Inserm History) website

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