A Brief History of Neonatology It is a

A Brief History of Neonatology It is a common myth that pediatrics has always existed and that neonatology is a spurious subspecialty that was spawned late in its glorious history. In fact, the opposite is true… pediatric cardiology, pediatric surgery, pediatric hematology, even genetics … they all got their starts from neonatology. Phillip V. Gordon Information in this talk has been heavily borrowed from Neonatology on the Web

Nothing happened during the dark ages 1200 s (the dark ages are over) Hospital for Foundlings, Pope Innocent III (Rome) Oldest reference to a caesarean section 715 -673 BC (the legend of Julius Cesar’s birth) Soranus of Ephesus wrote Gynecology which included a chapter on the care of the newborn 98 -138 AD 1630 (circa 1740) (dawn of the age of enlightenment) L'Hôpital des Enfants. Trouvés, (Paris) St Vincent De. Paul & The Daughters of Charity agrarian society transforming into an industrial society

Large cities become the engines of industrialization The impetus forceps was as much for the evacuation of the fetus (all too often dead) and survival of the mother as for improved viability 1 st diagnosis of Duodenal Atresia 1733 1 st diagnosis of Hirschsprung’s 1691 1650 The Foundling Hospital, London (founded in 1739) William Hogarth established the first model of a charitable hospital for children

Le Tour d'Abandon (The Desertion Tower), Paris 1810 -1860 By the 19 th century foundlings have become a government sanctioned industry (albeit a charitable and subsidized one)

1 st publication of correct average birth weight and length 1753 (Roederer – Germany) 5 ½ lbs Foundlings = the primary neonatal research population Francois Chassier recommends oxygen for the resuscitation of newborns (it is not utilized for another 70 years) 1780 (today’s average birth weight is 7 lbs) 1 st description of hypertrophic pyloric stenosis 1788 1 st description of Transposition of the Great Vessels 1797

Growing recognition of positive neonatal interventions 1834 (forceps deliveries) 1 st description of endotracheal intubation for newborn resuscitation Blundell 1803 1802 1 st description of hydrocephalus in infants Herberden (Scotland) Opening of the Hôpital des Enfants-Malades in Paris, (the 1 st children's hospital) 1 st surgical closure of omphalocele by Hey

1852 -1854 Great Ormond Street Hospital, London; Children’s Hospital of Philadelphia; and New York Nursing and Children’s Hospital are all founded GOSH 1847 1839 1851 First report of gavage feedings for infants First use of ether anesthesia in obstetrics 1 st description of prune-belly syndrome Ground swell of big city support for children’s hospitals CHOP NYNCH

Jean-Louis-Paul Denucé invents the first infant incubator 1857 1901 Pan Am Expo, Buffalo 1904, St Louis Fair Late 19 th century = the golden age of neonatology

1861 Late 19 th century = the golden age of neonatology WJ Little 1 st describes cerebral 1879 palsy Sigmund Franz Crede prescribes dilute silver 1882 nitrate for opthalmia neonatorium Bedeirt (gonorrhea) Heat treatment of milk for 2 hrs at 100 degrees C. for artificial feeding (although Louis Pasteur invented pasteurization 20 years earlier) 1888 Fallot describes his famous tetrology of congenital heart defects

Archibald E. Garrod postulates "inborn errors of metabolism" and Heidenhain their inheritance 1 st successful repair according to of congenital Mendel's Laws diaphragmatic 1908 hernia 1902 Continuation of the golden age of neonatology C. W. Townsend 1 st description of "hemorrhagic disease of the newborn“ 1894 Tarnier 1 st use of oxygen (O 2) in premature infants 1889 The father of genetics alkaptonuria

Ramstedt 1 st successful treatment of pyloric stenosis with pyloromyotomy 1912 Richter 1 st Transthoracic ligation of tracheoesophageal fistula 1913 William Ladd (father of pediatric surgery popularizes both procedures in the USA) Continuation of the golden age of neonatology J. B. Sidbury 1 st transfusion through the Umbilical Vein in Hemorrhage of the New-Born (Wilmington NC) 1919 H. Dam & W. W. Waddell discovery of vitamin K and treatment of coagulation abnormalities of the newborn 1936, 1937

Landsteiner & Levine Discovery of Rh factor Louis K. Diamond Gregg Established link between Rh Congenital cataracts due isoimmunization and to Rubella epidemic erythroblastosis fetalis & Clifford 1 st exchange transfusion via 1 st clinical recognition of umbilical vein as treatment for retrolental fibroplasia erythroblastosis fetalis 1941 1942, 1946 Carl Landsteiner Alexandar S Nadas starts the first pediatric cardiology program (CHOP) (focused on congenital heart disease) 1949 The father of pediatric hematology Continuation of the golden age of neonatology The father of pediatric cardiology

Smith Proposed withholding fluid in premature infants 1949 Patz 1 st RCT to link excessive O 2 to Emerson retinopathy of Invention of prematurity (ROP). high-frequency 1952 oscillatory ventilation (but not used in Gleiss infants) 1953 RCT: withholding fluid in immediate postnatal period not beneficial 1955 A new dark age emerges as interventions go awry (RDS and chronic lung disease become “incurable”) Silverman RCT: Sulfa drugs increase kernicterus 1956

Sister Jean Ward Serendipitous observation of effect of sunlight on indirect bilirubin level 1956 Introduction of Thalidomide 1957 Joan Hodgman Gray-Baby Syndrome due to use of prophylactic Mary Ellen Avery chloramphenicol Surfactant deficiency is 1959 the cause of respiratory distress 1959 Mother of phototherapy A black cloud persist despite remarkable advances

Patrick Bouvier Kennedy dies from RDS (34 weeks gestation / 2100 grams) Mildred Stahlman pioneers mechanical ventilation as therapy for infant with RDS Birth defects linked to thalidomide 1961 1960 A black cloud persist despite remarkable advances 1963 Now the world could watch as infants with RDS died not in hours, but days, weeks… months because of mechanical ventilation. The Kennedy’s experience spurred the Western World to find a cure for RDS.

Victor Freda develops Rhogam the prevalence of erthroblastosis starts to fall 1966 Rashkind technique of atrial septostomy developed as rescue therapy for transposition of the great vessels 1967 Wilmore & Dudtrick 1 st report of total parenteral nutrition for the neonate 1968 A black cloud persist despite remarkable advances

NICUs become “Chest Tube Meccas” in the 1970 s GA Gregory invents the Gregory Box for continuous positive airway pressure 1971 J. Kattwinkel A device for administration of continuous positive airway pressure by the nasal route 1973 2 NEJM case series demonstrate pharmacologic closure of the PDA with indomethacin (the therapy was immediately adopted around the world) 1976

Exosurf (an artificial surfactant) is shown to be effective by multinational RCTs and is approved by FDA 1990 -1991 High frequency oscillatory ventilators become commercially With the combination of pulse available Pulse oximetry, gentler ventilation 1990 widely strategies (including the concept available in of permissive hypercapnea) and newborns completion of the 30 year quest RCT: 1987 for artificial surfactant, cryotherapy for neonatologists go from saving retinopathy of near term infants to ratcheting prematurity down the gestational survival 1985 limits to the second trimester fetus. Cerebral palsy incidence is unchanged. Neonatology opens Pandora’s Box

P. V. Gordon et al. Multiple RCTs test demonstrate that early postnatal steroids in dexamethasone’s for combination with early attenuation of indomethacin increase chronic lung disease spontaneous intestinal ( associated with CP perforations & intestinal 1999 -2007 perforations) 1999 -2001 FDA approves Nitric Oxide for treatment of pulmonary hypertension in the What we seem to be learning in newborn the post surfactant age is that the 1997 important limits to neonatology L. Van Marter may not be viability, it may be the Cohort study capacity to develop an ex utero demonstrating fetus into a functional human being antenatal steroids who has meaningful quality of life. reduce the incidence We are in fact creating entirely of BPD new disorders in these survivors. 1990 Neonatology keeps prying open Pandora’s Box PV Gordon

What can we learn from history? 1) Neonatology has fathered most of the pediatric subspecialties we know today. 2) Much of our progress has come about because of society, not in spite of it. 3) Progress had not been always forward, but saltatory, with advances and set backs in accordance with the accuracy of our understanding of fetal and neonatal biology. 4) There are many Living Legends in Neonatology and there’s still plenty of room for others to join them.