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Background: Although a major cause of infant mortality for centuries, little research was done on the causes of infants' diarrhea. Artificial feeding, teething, and summer heat were believed to cause the severe disease that spared breastfed infants., Summary: Since antiquity, infants' digestive disorders were termed dyspepsia, flux of the belly, diarrhea, gastroenteritis, watery gripes, the runs, dysentery, or cholera, without definitions. Alois Bednar discerned 3 grades (dyspepsia, diarrhea, and cholera) of the same disease. Infants' neurologic symptoms were interpreted as alimentary toxicosis. Chronic diarrhea caused emaciation and dehydration. In 1950, Laurence Finberg found diarrhea with hypernatremia causing cerebral damage. Seasonal influence was known since Hippocrates. Baudelocque recommended obtaining infant milk fresh from the cow because it decomposes in the summer heat. In the cities, summer diarrhea caused a third of total infant mortality. Physicians debated whether heat acted directly on the infant or spoiled the food. The discovery of microorganisms in the 1860s revolutionized medical understanding. However, influential researchers such as Adalbert Czerny classified nutritional disturbances by assumed pathogenesis ("ex alimentation, ex infection, ex constitution"), but denied the possibility of bacterial infection via milk. Heating baby food, practiced for centuries, was introduced in Denmark, Sweden, and France, whereas in Britain and Germany, professional and public debate on pasteurization persisted., Key Messages: It took half a century to implement effective hygienic measures once the bacterial origin became known. Foodborne infection was rejected, and the prejudice that raw milk possesses essential "living" properties, adopted by influential scientists, contributed to delaying pasteurization., (© 2024 S. Karger AG, Basel.)

Background: Little is known about research in Foundling Hospitals during the 18th century., Summary: The London "Hospital for the Maintenance and Education of Exposed and Deserted Young Children" opened in 1741, after fundraising by the former shipmaster Thomas Coram and a Charter by King George II. From 1741 to 1756, fewer than 100 infants a year were admitted by lot. With onset of the Seven Years' War in 1756, the House of Commons resolved and financed the admission of all deserted babies. The number of admitted babies rose to 4,000 per year, and their mortality increased. The Institution was not intended as a research and teaching facility but soon became a site for gaining knowledge of young infants. Appointed physicians included Richard Conyers, William Cadogan, William Watson, and William Buchan. Their research focused on frequent conditions in the hospital's infirmary such as scabies, fever, measles, chilblains and scorbutic eruptions, and set standards for infant care and nutrition in the English-speaking world during the 18th century. They described the dangers connected with tight swaddling, meconium purgation, artificial feeding, and the difficulty to obtain wet nurses in the big cities. A major topic was their fight against smallpox, then fatal for 80% if infected infants, and the development of an effective technique of inoculation., Key Messages: Research at the London Foundling Hospital differed from modern understanding of controlled clinical trials but revealed systematic, hypothesis-driven approaches in the mid-18th century. As in other Foundling Hospitals, absent parental interference facilitated innovations., (© 2024 S. Karger AG, Basel.)

The 21st century's medicine is predominantly female: two thirds of medical students now are women. In 375 BCE, Plato argued for equal education for male and female professions, explicitly physicians. In Greece and Rome, tombstones testify for patients' gratitude to women physicians. Christianization opened an era of female subordination. When universities established faculties of medicine during the 13th century, women were excluded and had no place where they could study medicine. Since 1850, female medical studies have been debated. Zürich admitted women from 1864, Paris from 1866. Up until the 1920s, treatment of newborns - especially preterm infants - was in the domain of obstetricians. When pediatricians accepted responsibility for sick newborns, women founded hospitals and public health facilities for infants. After WW2, women took leading roles in research. Their share within pediatrics increased from below 10% to above 60%. But they achieved less than 20% of full professor or chair positions in Europe and less than 35% in the US. Female neonatologists reached fewer positions in editorial boards, authorships, h-factors, keynote lectures, and research grants than did male colleagues. Women pediatricians earned 24% less than did male colleagues. When adjusted for labor force characteristics, the pay gap was still 13%. Women can augment their career chances by setting targets, seeking mentorship, and strengthening self-confidence. Women's careers should be effectively accelerated by institutional support: research offers, part-time work, paid research time, maternity/paternity leave, and support for childcare. Research-oriented neonatology cannot afford to lose female talents., (© 2023 S. Karger AG, Basel.)

Abandoning infants was a heritage of the Roman Empire. Foundling hospitals were established in Italy earlier and in greater number than in other countries; their goal was to prevent infanticides. The Foundling Hospital in Rome, established in the Santo Spirito Church in 1204, paved the way toward modern hospital care and child protection. The Order of the Holy Spirit was appointed by Pope Innocent III to care for foundlings, and set up a network of infant nurseries all over Europe. Poor unmarried pregnant women received obstetric services free of charge. Infants were admitted anonymously by the ruota, a baby hatch or turning wheel. The Order's rule regulated infants' admission, care, nutrition by wet nurses, and boarding out to foster families in the countryside. Chief physicians of the Santo Spirito Hospital were often Sapienza University professors and/or personal physicians to the Popes. Among them were Realdo Colombo, Andrea Caesalpino, Giovanni Lancisi, Giuseppe Flajani, Domenico Morichini, and Tommaso Prelà. They made major scientific progress in anatomy and surgery: descriptions of the pulmonary blood transit, embryonic formation, fetal circulation, malaria transmission from mosquitos, and surgery for congenital malformations such as hydrocephalus, anal atresia, and cleft lip. Per year, 800-1,000 exposed infants were admitted. Despite sufficient funding and meticulous regulation of care and nutrition, mortality in the hospital during the first month of life was around 70%; the causes were neglected surveillance, cleanliness, and artificial nutrition. The institution persisted for more than 700 years due to numerous connections with the Vatican., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Abandoning undesired newborn infants was a Roman form of family limitation. They were exposed or given to foster mothers. Christianization alleviated their lot when in 374 CE, Emperor Valentinian's law provided some protection. The Milan Foundling Hospital was established in 787 CE. When the Carolingian Empire fell apart during the 10th century, monastic networks (the Holy Spirit Order and Daughters of Charity) took over social support for the poor, the sick, and the insane. Foundling hospitals proliferated in Italy between the 13th and 15th centuries, in France during the 16th and 17th, and in Germany and Austria in the 18th century. Metropolitan hospices admitted thousands of infants each year. Most were not "found" exposed but were admitted anonymously via a revolving box or registered in an open office. Soon after admission, they were transported for foster care to wet nurses in villages. Sick infants, especially those suspected of suffering from syphilis, were denied the breast, and artificial feeding was tried with little success. Official death statistics were falsified by relating infant deaths not to admissions but to the total number of children cared for. Over 60% died during their first year of life, mostly from pre-admission problems such as malformation, hypothermia, and disease; from poor hygiene in overcrowded wards; and from artificial feeding. Although not intended for that purpose, the hospices became medical research institutions when in late 18th century, physicians and surgeons were employed by maternity and foundling hospitals., (© 2022 S. Karger AG, Basel.)

This paper investigates causes and consequences of the prejudice towards extramaritally born infants. The main rationale for such defamation seems to have been religious teachings. However, rather than a matter of sexual morals, "illegitimacy" became an economic issue when infants were maintained on taxpayers' money. Under most civil laws, "bastards" could not inherit. In German-speaking states, they were excluded from the guilds, which deprived them of professional training. They found refuge in "dishonest" professions and life in poverty. In the Late Middle Ages, a third of the population was probably born extramaritally. From 1400 to 1600, the illegitimacy ratio dropped markedly, but from 1650 to 1850, it seems to have gradually risen from around 5 to 9% in most European states. French authorities did not search for the putative father but offered the mother the possibility to abandon her child in a foundling asylum. In 1990, the term "illegitimacy" was replaced by "born out of wedlock." After an extramarital birth, the infant mortality rate was elevated by 40-50% above that of maritally born infants. After 1960, effective contraception changed sexual morals, but marital fell more than extramarital fertility. Paternity was no longer uncertain. The Catholic church's influence decreased; and legal reforms protected the infant. Today, half of all infants in Europe are born out of wedlock; that is no longer a proxy for poverty., (© 2022 S. Karger AG, Basel.)

Given the high rate of alcoholism throughout history, its effects on the fetus may have existed for millennia. But, the claim that Greeks and Romans were aware of fetal alcohol syndrome rests on incorrect citations. From 1725, maternal alcohol consumption was associated with retarded fetal growth and neurological anomalies. From 1809, scientists followed Lamarck's theory that the disorders parents acquire during their lifetime are passed on to their offspring. Fetal effects were thought to be inherited mainly from the father. During the 19th century, parental alcoholism became associated with malformations. In 1915, Ballantyne distinguished genetic influence via germ cells from toxin's effect on the embryo. Fetal alcohol syndrome was characterized by Rouquette [Influence de la toxicomanie alcoolique parentale sur le développement physique et psychique des jeunes enfants] in 1957 and Lemoine et al. [Ouest Medical. 1968;21:476-482] in 1968 as consisting of 4 features: (A) facial anomalies (narrow forehead, retracted upper lip, and cupped ears), (B) severe growth retardation (prenatal and postnatal), (C) malformations (limbs, cardiac, and visceral), and (D) central nervous system anomalies (hyperexcitability and mental retardation). But, their studies, written in French, remained disregarded. In 1973, Jones et al. [Lancet. 1973;302:999-1001] reported "the first association between maternal alcoholism and aberrant morphogenesis in the offspring." The history of fetal alcohol syndrome reveals shortcomings in citation practice. Alleged quotations remained unverified, non-English publications neglected, and short quotations taken out of context. Prejudiced by religious and abstinence groups, reports on alcohol damage to the unborn were fraught with emotions, moralizing, social implications, and presentism, the interpretation of past events with present knowledge., (© 2021 S. Karger AG, Basel.)

In most societies, devices evolved to enhance the mother's working capacity. This article depicts the cradle's development in some countries and delineates the scientific debate that led to its demise in the 19th century. A few basic forms of infant cots survived the centuries from antiquity: the carrying board, trough, hammock, sling, transverse rockers, and forward rockers. Romans discerned 2 types: the cuna stood on the floor and was moveable by wooden rockers. Lecti pensiles were suspended beds. Cradleboards of Native Americans revealed remarkable variety of shapes and decorations. The cradle's hood was a 16th century development, intended to protect the baby's face from flies, sunlight, and the evil eye. Already in the second century CE, Galen mentioned controversies about rocking. A fervent debate began in the 18th century. Propagators reasoned that rocking perpetuates habitual fetal movement, exercises the child, and avoids the need for somniferous drugs. Opponents claimed that rocking is dangerous, producing an unnatural sleep harmful to the brain, and impeding milk digestion. In the 20th century, cradles were replaced by pushchairs and prams, but they did not disappear. Despite centuries of debate, robust studies have never been conducted, and it remains unclear whether rocking has any benefit or harm for the infant., (© 2021 S. Karger AG, Basel.)

Infant baptism originated when St. Augustine proclaimed the doctrine of original sin in 412 CE. Neonates stillborn or deceased before baptism were declared to go down to Hell and were buried outside of sacred ground. From the 15th century, parents carried these infants to "respite sanctuaries" in remote mountain chapels, where miraculous images were believed to revive the infant in order to allow baptism and a Christian burial. Monasteries made fortunes out of the parents' anguish. In 1528, the abuse of the Oberbüren image ignited iconoclasm and heralded the beginning of the Reformation. From 1740, Pope Benedict XIV opposed the sanctuaries, especially Ursberg in Swabia, declaring as invalid any apparent signs of life, e.g., changes in skin color, a change from rigidity to flexibility, blood flowing from the nose, sweat on the skin, cessation of a cadaveric smell, and the movement of a feather held at the infant's mouth. Only crying and sounds of respiration remained valid signs of revivification. The debate ran for centuries, highlighting the difficulty of distinguishing a stillborn from a liveborn baby before the stethoscope became available. The existence of respite sanctuaries is an illustration of the failure of the doctrine of original sin, which was never accepted by the pious., (© 2018 S. Karger AG, Basel.)

Since antiquity, cot death has been explained as accidental suffocation, overlaying, or smothering. Parents were blamed for neglect or drunkenness. A cage called arcuccio was invented around 1570 to protect the sleeping infant. Up to the 19th century, accidents were registered as natural causes of death. From 1830, accidental suffocation became unacceptable for physicians and legislators, and "natural" explanations for the catastrophe were sought, with parents being consoled rather than blamed. Two assumed causes had serious consequences: thymus hyperplasia was irradiated, causing thyroid cancer, and the concept of central apnea was widely accepted, which led to home monitors and distracted from epidemiological evidence. Prone sleeping originated in the 1930s and from 1944, it was associated with cot death. However, from the 1960s, many authors recommended prone sleeping for infants, and many countries adopted the advice. A worldwide epidemic followed, peaking at 2‰ in England and Wales and 5‰ in New Zealand in the 1980s. Although epidemiological evidence was available by 1970, the first intervention was initiated in the Netherlands in 1989. Cot death disappeared almost entirely wherever prone sleeping was avoided. This strongly supports the assumption that prone sleeping has the greatest influence on the disorder, and that the epidemic resulted from wrong advice., (© 2017 S. Karger AG, Basel.)

Rites of passage mark important changes during human life and, for the neonate, its transition from intrauterine life into society. Their original intent was to purify the body from blood and meconium. But the cleansing rites had a spiritual dimension from the very start. When the rites of Mesopotamian, Egyptian, Jewish, Greek, Roman, Hindu, Nordic, Muslim, Maya, and Christian cultures are briefly compared, they reveal a remarkable similarity. What most rites had in common was the cleansing of the body, or sprinkling it with water; special clothing; the exorcism of evil spirits; blessings and prayers for good spirits; and a name-giving ceremony and a feast for family, relatives, and friends. Before this rite, the infant's social existence was incomplete and it could easily be abandoned or killed, as was usual in cases of severe malformations. Infant baptism originated in the 4th century CE with the concept of original sin. Emergency baptism originated in the 12th century and had a profound influence on the development of obstetrics and neonatal care. Rites of passage defined, but also set an end to, the liminal status between life and death in a phase of high mortality and partial personhood, and granted the right to live for the infant., (© 2017 S. Karger AG, Basel.)

This is the third of three papers investigating the legislative history concerning infanticide. After Antiquity and the Middle Ages, this paper focuses on legislative reforms during the last 400 years. Despite dreadful punishment, the practice remained frequent until safe abortion became available. In the 17th century, the rate of executions of women for this crime was 1 per 100,000 inhabitants. The actual incidence greatly exceeded this figure. The death penalty failed to deter, and punishing fornication promoted rather than prevented infanticide. Well into the 18th century, severely malformed infants were killed. The lung flotation test, albeit unreliable, was used to save the mother from the death penalty. When the motives for infanticide - poverty, shame, despair, and preserving honour - became understood in the late 18th century, the image of the 'child murderess' changed, and infanticide shifted from constituting a capital crime to a privileged delict. Illegitimate pregnancy was no longer punished, and lying-in hospitals for pregnant unmarried women and foundling hospitals for their children were established. Specific infanticide laws were issued in Prussia in 1756, Britain in 1803, and France in 1811. Once psychosis and denial of pregnancy became understood, severe penalties were no longer issued. The justifications for lenient legislation included social circumstances, difficult proof, and curtailed protection of the newborn due to its illegitimacy, helplessness, and diminished awareness. Thoughts on the limited right to live of newborn infants are still hampering ethical decisions when the beginning and end of life are near each other., (© 2016 S. Karger AG, Basel.)

This is the first of three papers investigating changes in infanticide legislation as indicators of the attitude of states towards the neonate. In ancient East Asian societies in which the bride's family had to pay an excessive dowry, selective female infanticide was the rule, despite formal interdiction by the law. In Greece and Rome children's lives had little value, and the father's rights included killing his own children. The proportion of men greatly exceeding that of women found in many cultures and epochs suggests that girls suffered infanticide more often than boys. A kind of social birth, the ritual right to survive, rested on the procedure of name giving in the Roman culture and on the start of oral feeding in the Germanic tradition. Legislative efforts to protect the newborn began with Trajan's 'alimentaria' laws in 103 CE and Constantine's laws following his conversion to Christianity in 313 CE. Malformed newborns were not regarded as human infants and were usually killed immediately after birth. Infanticide was formally outlawed in 374 CE by Emperor Valentinian., (© 2015 S. Karger AG, Basel.)

This is the second of three papers investigating the legislative history concerning infanticide. It compares the efforts of various states to protect the newborn infant between 534 and 1532 CE. When the Roman Empire collapsed in the 5th century, the jurisdiction of infanticide was relegated to the church, which regarded carnal delicts a sin rather than a crime. The punishment - public penance of the mother for 7-15 years - was milder than that which the murder of an adult would incur. The Council of Florence decreed in 1439 that the souls of children who died without having been baptized descend to hell. This turned infanticide from a penitential sin to the most heinous of all crimes. The states passed laws that abominated infanticide even more than the murder of older humans and punished women with ever more cruel forms of execution. Towards the men, however, who usually abandoned the women they had impregnated, the laws were lenient. Churches and society continued to vilify illegitimate birth, thus enhancing rather than preventing infanticide. The Habsburg-German legislation of 1532 ordained to torture any woman who had concealed pregnancy and birth and claimed the infant was stillborn. Legislation developed similarly in other countries, albeit at a different speed. French (1556) and British (1623) legislation reversed the burden of proof and demanded the death penalty for concealing pregnancy and birth when a dead infant was found., (© 2015 S. Karger AG, Basel.)

Hemorrhages occurring in the newborn without trauma have been observed by obstetricians since the 17th century, but have been considered different diseases depending on their location. Umbilical hemorrhage associated with obstructed bile canals was described by Cheyne in 1802. Grandidier in 1871 and Townsend in 1894 grouped together various forms of neonatal bleeds and associated them with disturbed coagulation. When the clotting system became better understood in the last decade of the 19th century, effective symptomatic treatment was developed: gelatin, serum injection, and the transfusion of fresh blood. In 1935, Dam detected the function of vitamin K in the coagulation system and 4 years later, Waddell introduced vitamin K administration into therapy and prevention of neonatal hemorrhagic disease. Kernicterus occurred when high doses of synthetic water-soluble vitamin K analogues were given to preterm infants, reminding physicians that progress in neonatal therapy rests on the cornerstones of controlled trials and follow-up., (© 2015 S. Karger AG, Basel.)

Industrialized food production first appeared in 1856, pioneered by Borden in the USA, Liebig in Germany, Nestlé in Switzerland, and Mellin in the UK. Their products differed remarkably and deviated from human and cow's milk, and physicians discussed the importance of minute variations in protein, fat and carbohydrates. Proprietary formulas were free of bacteria, and the companies prospered with mass production, international marketing and aggressive advertising. From 1932 on, medical societies restricted advertising to the laity. In 1939 Williams in Singapore and in 1970 Jelliffe in Jamaica suspected that commercial formula may be increasing infant mortality in the Third World. Breastfeeding continued to decline during the early 20th century, falling in 1970 below 10% in the USA. The Swiss 'Third World Group' and the US 'Infant Formula Action Coalition' linked infant mortality and industry marketing in the Third World. The controversy of 1970-1984 led to the WHO Code, which regulated the advertising and marketing of baby food. This was one of several public health statements contributing to the resurgence of breastfeeding., (© 2014 S. Karger AG, Basel.)

This paper collects information on artificial infant feeding published before 1860, the year when commercial formula became available. We have extensive artifactual evidence of thousands of feeding vessels since the Bronze Age. Special museum collections can be found in London, Paris, Cologne, Fécamp, Toronto, New Mexico, and elsewhere. The literature on the use of animal milk for infant feeding begins with Soranus in the 2nd century CE. Literature evidence from the very first printed books in the 15th century proves that physicians, surgeons, midwives, and the laity were aware of the opportunities and risks of artificial infant feeding. Most 17th to 19th century books on infant care contained detailed recipes for one or several of the following infant foods: pap, a semisolid food made of flour or bread crumbs cooked in water with or without milk; gruel, a thin porridge resulting from boiling cereal in water or milk, and panada, a preparation of various cereals or bread cooked in broth. During the 18th century, the published opinion on artificial feeding evolved from health concerns to a moral ideology. This view ignored the social and economic pressures which forced many mothers to forego or shorten breast-feeding. Bottle-feeding has been common practice throughout history.

Artificial feeding of infants, called hand-feeding, was unsafe well into the 19th century. This paper aims to identify technical innovations which made artificial feeding less dangerous. In rapid succession from 1844 to 1886, the vulcanization of rubber, production of rubber teats, cooling machines for large-scale ice production, techniques for milk pasteurization, evaporation and condensation, and packing in closed tins were invented or initiated. Remarkably, most of these inventions preceded the discovery of pathogenic bacteria. The producers of proprietary infant formula made immediate use of these innovations, whereas in the private household artificial feeding remained highly dangerous - mostly because of ignorance about bacteria and hygiene, and partly because the equipment for safe storage, transport, preparation and application of baby food was lacking.

Background: Industrialization and urbanization jeopardized infant nutrition during the 19th century. Cow's milk was produced in the cities or transported long distances under suspect conditions. Milk was contaminated with bacteria or adulterated with water, flour, chalk and other substances. When distilleries proliferated in the metropoles, their waste slop was fed to cows which then produced thin and contaminated swill milk., Summary: Following a press campaign in the USA, the sale of swill milk was prohibited by law in 1861. Bacterial counts became available in 1881 and helped to improve the quality of milk. Debates on pasteurization remained controversial; legislation varied from country to country. Disposal of the wastewater of millions of inhabitants and the manure of thousands of cows was environmentally hazardous. It was not until 1860 and after several pandemics of Asiatic cholera that effective sewage systems were built in the metropoles. Milk depots were established in the USA by Koplik for sterilized and by Coit for certified milk. In France, Budin and Dufour created consultation services named goutte de lait, which distributed sterilized milk and educated mothers in infant care., Message: Multiple efforts to improve milk quality culminated in the International gouttes de lait Congresses for the Study and Prevention of Infantile Mortality.

Before the microbiologic era, venereal diseases were poorly distinguished. Congenital syphilis was believed to be transmitted during conception by the father's sperm, during delivery in the birth canal, or from infected milk or breasts. The most frequent maternofetal transmission was not considered because the mother's primary infection remained undiagnosed. The concept of treating infants with mercury transmitted by nurses' milk prompted the founding of a specialized infant hospital in Vaugirard in 1780: lactating syphilitic women received mercury orally and by rubbing it into the skin. Their own infant and a second infected infant from the foundling hospital were believed to be cured by their milk. Underwood described snuffles in 1789 and Bertin periosteal bone disease in 1810. Tardive congenital lues with keratitis, deafness, and notched upper incisors were described by Hutchinson in 1863. Feeding remained difficult, as wet nursing transmitted syphilis to the nurse and other infants. Specialized institutions tried goat or donkey milk. A debate between contagionists assuming exclusively maternal infection and hereditists assuming germinal transmission by the father's sperm continued throughout the 19th century. Schaudinn and Hoffmann identified Spirochaeta pallida in 1905. When Ehrlich discovered the efficacy of salvarsan in 1910, Noeggerath treated infants with the new drug, pioneering the injection into scalp veins. In 1943, Lentz and Ingraham established penicillin treatment for congenital syphilis. Whereas this drug effectively prevented maternofetal transmission, treating infants remained difficult due to the Jarisch-Herxheimer reaction., (Copyright © 2013 S. Karger AG, Basel.)

Treatment of sick neonates originated in maternity and foundling hospitals in the 19th century. Nosocomial infections and difficult logistics of wet-nursing prevented admission of neonates in most children's hospitals well into the 20th century. In this article, 31 hospitals are described, all located in large cities, in which preterm and sick neonates were treated before the Great Depression. Even though mostly initiated by private charity, these institutions performed research right from the start. Topics included warming and feeding preterm infants, collecting and distributing human milk, developing and storing breast milk substitutes, prevention of rickets and nosocomial infections, maternal and public education regarding infection control, pathoanatomic characterisation of diseases and malformations and epidemiologic studies of infant mortality. These pioneering hospitals, their founding dates, researchers and classic publications are presented in a table., (Copyright © 2012 S. Karger AG, Basel.)

Before safe artificial nutrition, refrigeration, and microorganisms became known, thrush was a severe and frequently lethal disease in foundling hospitals. Overcrowded and understaffed, these institutions were the ideal breeding ground for this disease. Malnutrition, especially when breastfeeding was denied, contributed to the fatal course. Nosocomial infections and high mortality led to a prejudice against infant hospitals in the late 19th century. Candida albicans was discovered in 1840 when a cooperation at the Paris Foundling Hospital between the Hungarian emigrant David Gruby and the Swede Frederik Berg led to this organism being the first pathogen to be identified. After World War II, Candida infections increased with the use of antibiotics. The disease became less threatening after the development of nystatin, the result of an interdisciplinary cooperation in New York between the microbiologist Elizabeth Hazen and the biochemist Rachel Brown., (Copyright © 2011 S. Karger AG, Basel.)

Wet nursing was widely practiced from antiquity. For the wealthy, it was a way to overcome the burdens of breastfeeding and increase the number of offspring. For the poor, it was an organized industry ensuring regular payment, and in some parishes the major source of income. The abuse of wet nursing, especially the taking in of several nurslings, prompted legislation which became the basis of public health laws in the second half of the 19th century. The qualifications demanded from a mercenary nurse codified by Soran in the 2nd century CE remained unchanged for 1,700 years. When artificial feeding lost its threat thanks to sewage disposal, improved plumbing, the introduction of rubber teats, cooling facilities and commercial formula, wet nursing declined towards the end of the 19th century., (Copyright © 2012 S. Karger AG, Basel.)

By 1769, it was known to Morgagni that the ductus arteriosus may persist until adulthood. In 1835, Jörg linked delayed postnatal closure with disturbed respiration, a discovery that was afterwards forgotten for a century. When blood gas analysis became available, the association between persisting patency and diminished oxygenation resurfaced. When it became known that prostaglandins played a role in maintaining ductal patency, the development of pharmacologic intervention with cyclooxygenase inhibitors immediately followed. This rapid progress was due to the interaction between basic science, pediatric cardiology, and neonatology disciplines at the Cardiovascular Research Institute in San Francisco, coordinated by Julius Comroe, as well as President Kennedy's foundation of the National Institute of Child Health and Development. This series of events exemplifies how clinical research became an integrated managed multidisciplinary endeavor in the 20th century., (Copyright © 2010 S. Karger AG, Basel.)

Ductus arteriosus and foramen ovale were described by Galen without understanding their functions. His beliefs in soul localization and spiritization within the left ventricle established religious pneumatology which became a theological need in the Middle Ages. Pulmonary transit was recognized by Servetus and Colombo after the Reformation around 1550. This prompted Harvey's full understanding of the fetal circulation. Botallo did not describe the ductus arteriosus, but in 1564 redescribed the foramen ovale, making his way into the nomina anatomica by mistake. Most authors of the 19th and 20th century believed ductal patency to be passive, and postnatal closure to be an active process, explained by mechanical theories. After the discovery of prostaglandins by Bergstrom and Vane, Coceani proved that ductal patency is maintained by the relaxant action of prostaglandins., (Copyright © 2010 S. Karger AG, Basel.)

Tongue-tie, or ankyloglossia, is poorly defined and involves a short, thick, fibrosed, or fixed lingual frenulum. Operative interventions were proposed already in Greek medicine. In the Middle Ages, competition arose between midwives, who used their nails to detach the frenulum, and surgeons, who were allowed to use instruments. During the last century, the justification for frenotomy shifted from improved language to enhanced feeding. Despite the high frequency of the intervention, little research has been performed on its benefit, which remains a controversial topic among different groups of health professionals., (Copyright 2009 S. Karger AG, Basel.)

Necrotizing enterocolitis (NEC) is not a new disease but one that has been reported since special care units began to house preterm infants. It was observed in foundling hospitals in Paris [Billard, 1828] and Vienna [Bednar, 1850] and, as it occurred in clusters, was regarded as a nosocomial infection in the infant hospitals of Zurich [Willi, 1944] and Berlin [Ylppo, 1931]. Clinical and patho-anatomic characterization was achieved by Schmidt and Quaiser in 1952. The unproven hypothesis of mesenteric hypoperfusion as a major etiological factor arose from animal models and analogous perforating disorders in term infants. Despite similarities between NEC and clostridial infections, few studies employed anaerobic culture techniques. The pathogenesis remains unclear and its distinction from related disorders uncertain. It is unlikely that strategies to prevent NEC will be successful unless the disease is better understood., (Copyright 2009 S. Karger AG, Basel.)

Endotracheal intubation to resuscitate neonates was used by Scheel in 1798. A century before endotracheal anesthesia was developed, inventive obstetricians constructed devices for endotracheal intubation of infants and mastered their insertion, localization, and airtight sealing. Fell's laryngoscope, Magill's intubation forceps and tissue-friendly materials were significant contributions of the 20th century to endotracheal intubation of the newborn. The striking absence of scientific studies on the most efficient resuscitation techniques for neonates can be explained by the difficulty to adjust for the personal skills of the resuscitator.

Oxygen was used in neonatal resuscitation from 1780, within 5 years of its detection. It rapidly gained general acceptance and infiltrated delivery rooms and, a century later, neonatal special care units. After 217 years without scientific evidence, the use of oxygen for neonatal resuscitation has recently been questioned. Continuous distending airway pressure for oxygen administration was available at the beginning of the 20th century, but was not widely accepted. Alkali and analeptic drugs gained widespread but short-lived use after the Second World War., ((c) 2008 S. Karger AG, Basel.)

The construction of manual ventilators by Hunter, Chaussier, and Gorcy seemed to set the stage for artificial ventilation of the neonate at the end of the 18th century. When Leroy d'Etiolles recognized pneumothorax as a complication of ventilation in 1828, the Paris Academy of Science advised against positive pressure ventilation. Indirect techniques like that of Silvester or the Schultze swingings gained widespread acceptance and prevailed until the First World War. Modern ventilators were developed following the poliomyelitis epidemics in the 20th century., ((c) 2008 S. Karger AG, Basel.)

Breast-fed preterm infants often show a better outcome, partly ascribed to the benefit of insulin-like growth factors (IGFs) and their binding proteins (IGFBP). We compared IGF-I, IGF-II, IGFBP-2 and IGFBP-3 levels, measured by radioimmunoassays in milk samples from 30 mothers of preterm (<31 weeks) and from 19 mothers of term (>37 weeks) infants at days 7 and 21 postpartum. Proteolysis of IGFBP-2 within mother's milk and digestion of (125)I-IGF-II and (125)I-IGFBP-2 by gastric juice from neonates were assessed by electrophoretic techniques. Mean concentrations did not differ between preterm and term milk: IGF-I (2.8 +/- 0.2 vs. 2.3 +/- 0.1 ng/ml), IGF-II (12.0 +/- 0.4 vs. 12.2 +/- 0.5 ng/ml), IGFBP-3 (100.0 +/- 5.1 vs. 80.0 +/- 5.8 ng/ml), but did so for IGFBP-2 (3,144 +/- 172 vs. 2,428 +/- 188 ng/ml, p < 0.02). Immunoblots revealed 42% (p < 0.05) more IGFBP-2 fragments of 14 and 25 kDa in preterm milk. Incubation with gastric juice caused cleavage of (125)I-IGFBP-2 and partial cleavage of (125)I-IGF-II. Mutual complexation protected IGF-II and IGFBP-2 from cleavage, suggesting that both are likely to arrive in the bowel in an intact form to exert promotive effects. The results provide further evidence that IGFBP-2 and IGF-II in breast milk are relevant factors for the early development of preterm infants., (Copyright 2007 S. Karger AG, Basel.)

Background: Chorangiomas are villous capillary tumors of the placenta with high impact on neonatal morbidity and mortality. Cardiac complications have occasionally been reported., Objective: To elucidate clinical features, diagnosis and treatment of cardiac failure caused by chorangiomas., Method: We report a case of a newborn, in whom massive chorangiomas were associated with severe cardiac failure, anemia, and thrombocytopenia., Results: Chorangiosis was not diagnosed prenatally. The pre-existing cardiac failure of the infant deteriorated soon after birth. Despite the severe stage, cardiac failure was reversible with intensive medical treatment including phosphodiesterase inhibitor. Complete recovery with no signs of cardiomyopathy was confirmed at the age of 5 months., Conclusions: Severe cardiac failure in the neonate can be caused by chorangiosis. The time of diagnosis and treatment seems to be critical for the outcome of the infant. Prenatal treatment interventions should be considered., (Copyright (c) 2007 S. Karger AG, Basel.)

Background: Elevated serum concentrations of S-100B, a 21-kDa protein expressed in astroglial cells, has been used to assess cerebral damage after head trauma, infection, ischemia, and perinatal asphyxia., Objective: As S-100B is eliminated by the kidneys, we investigated the feasibility of measuring S-100B in urine of newborns with severe perinatal asphyxia, and in very low birth weight (VLBW) preterm infants at risk for neurodevelopmental impairment., Methods: We first analyzed urine samples of 8 term or near-term newborns without major medical problems, followed by urine samples of 2 term newborns with severe birth asphyxia, and finally urine samples of 8 VLBW (gestational age 24-28 weeks) infants collected every 4 h for up to 10 days., Results: Urinary S-100B concentrations in 8 term or near-term newborns without major medical problems were consistently <1 microg/l. In 2 term newborns with severe asphyxia (Apgar 0/0/0 and 0/2/4) who subsequently had widespread cerebral damage on magnetic resonance imaging, peak urinary S-100B concentrations on the first day of life were 28.1 and 28.4 microg/l, respectively. In 5/8 VLBW infants, urinary S-100B was> microg/l in samples obtained on the first day of life (range 1.2-44.9 microg/l, median 6.8 microg/l). Peak S-100B in urine samples collected during the first 12 h of life were negatively related to gestational age (R(s)=-0.882, p=0.009). Three of the 8 preterm infants had peak urinary concentrations>0 microg/l but neither ultrasound signs of brain damage nor neurodevelopmental delay at 1 year corrected age., Conclusions: The determination of urinary S-100B concentrations might be helpful in term infants with severe asphyxia, while high urinary S-100B concentrations in preterm infants are to be attributed to immaturity., (Copyright (c) 2006 S. Karger AG, Basel.)

Remarkable insight into disturbed lung mechanics of preterm infants was gained in the 18th and 19th century by the founders of obstetrics and neonatology who not only observed respiratory failure but also designed devices to treat it. Surfactant research followed a splendid and largely logical growth curve. Pathological changes in the immature lung were characterized in Germany by Virchow in 1854 and by Hochheim in 1903. The Swiss physiologist von Neergard fully understood surfactant function in 1929, but his paper was ignored for 25 years. The physical properties of surfactant were recognized in the early 1950s from research on warfare chemicals by Pattle in Britain and by Radford and Clements in the United States. The causal relationship of respiratory distress syndrome (RDS) and surfactant deficiency was established in the USA by Avery and Mead in 1959. The Australian obstetrician Liggins induced lung maturity with glucocorticoids in 1972, but his discovery was not fully believed for another 20 years. A century of basic research was rewarded when Fujiwara introduced surfactant substitution in Japan in 1980 for treatment and prevention of RDS., (Copyright 2005 S. Karger AG, Basel)

Thrombopoietin (TPO) concentrations were determined in umbilical cord plasma of 121 healthy term newborns. The lower detection limit of the enzyme immunoassay employed was 32.5 pg/ml. Median cord plasma TPO concentration was 78 (interquartile range 55-107) pg/ml. 95th percentile was 255 pg/ml. In only 8% (10/121), TPO was below the detection limit compared to 81% of healthy adults (25/31). In cord blood and adult controls, there were no significant correlations of TPO with platelet count or mass.

Complete blood counts (CBC) of umbilical cord blood from 123 healthy term newborns were simultaneously performed with two different cytometers using laser as a light source. Medians (95% range) were: WBC 14.2 (7.8-24.3) x 10(9)/l, platelets 265 (174-363) x 10(9)/l, Hb 15.7 (12.5-18.2) g/dl, RBC 4.6 (3.9-5.5) x 10(12)/l, MCV 106 (95-113) fl, PCV 0.49 (0.40-0.56), and MCH 33.8 (30.3-36.4) pg. Reticulocytes were 149 (95-212) x 10(9)/l or 3.3 (2.0-4.7)%; erythroblasts 5 (0-24) per 100 WBC or 0.53 (0.00-3.20) x 10(9)/l. The counters agreed well except for MCHC. WBC counts showed the smallest difference irrespective of erythroblast number; platelets showed the largest difference. The lower limit for normal Hb should be fixed at 12.5 g/dl for the adequate diagnosis of anaemia from cord blood of term newborns.

Unlabelled: Surfactant bolus instillation may be associated with a drop in blood pressure. Platelet-activating factor (PAF) has been found in surfactant preparations. The aim of this study was to evaluate rapid tracheal infusion of surfactant during 5 min as an alternative to bolus instillation and to examine whether a PAF receptor antagonist is able to prevent the decrease in blood pressure., Methods: Surfactant deficiency was induced in 16 adult rabbits by lung lavages with saline. Six animals received a bolus of a porcine surfactant preparation (Curosurf (CS); 200 mg/kg), labeled with red microspheres to assess pulmonary distribution. In another 5 rabbits, the same amount of labelled CS was instilled by tracheal infusion within 5 min. A third group of 5 animals received 3 mg/kg body weight of the PAF antagonist WEB 2170 before CS bolus instillation., Results: After CS bolus administration, mean PaO2 increased by 44.7 +/- 8.3 kPa (mean +/- SD) within 2 min and remained at this level. Mean arterial blood pressure dropped transiently by 2.3 +/- 2 kPa within 5 min. Pulmonary distribution of surfactant was even. After infusion, mean PaO2 rose by 22.4 +/- 16.3 kPa within 15 min. Blood pressure dropped by 1.8 +/- 1.1 kPa within 15 min. The distribution was extremely uneven. Blood pressure decreases also occurred after pretreatment with PAF receptor antagonist., Conclusion: Rapid tracheal infusion of surfactant results in poorer oxygenation, an inhomogeneous distribution and a similar decrease in blood pressure compared to the bolus instillation method. Blood pressure changes could not be prevented by a PAF receptor-specific antagonist.

Fifteen preterm infants suffering from respiratory distress syndrome were randomly allocated to receive either high-dose (200 mg/kg) or low-dose (100 mg/kg) surfactant treatment. Retreatments were done with the low dose. Blood pressure, blood gases and cerebral blood flow velocities were determined before and after 24 bolus instillations. With the high dose mean blood pressure and mean cerebral blood flow velocity dropped significantly. With the low dose only mean cerebral blood flow velocity decreased; the course was unrelated to blood pressure or PCO2 fluctuations. The mechanisms leading to the observed circulatory changes after surfactant instillation remain unclear.

Long-term variability (LTV) of heart rate was calculated continuously by a microprocessor in 25 preterm infants undergoing indomethacin treatment for closure of patent ductus arteriosus (PDA), in 24 preterm infants without signs of PDA, and in 10 neonates treated with prostaglandin E1 for cyanotic heart malformation. In infants with patent ductus arteriosus, LTV was lower than in controls. Following indomethacin, LTV increased most markedly (from 1.5 to 3.2; p less than 0.01) in infants with improved ventilation. The increase was less marked (from 1.8 to 2.5; p less than 0.05) in infants whose degree of respiratory failure did not change. LTV remained largely unchanged in infants who deteriorated. In 9 out of the 10 neonates treated with prostaglandin E1, LTV increased. We conclude that LTV corresponds to brain stem oxygenation and may be a useful tool to monitor treatment of PDA.

A new amino acid solution (Aminopäd 5% and Aminopäd 10%) was used for intravenous feeding of 240 preterm and term newborn infants in 4 hospitals. Indications, dosages and infusion sites were up to the policies of the 4 hospitals. Plasma amino acid concentrations were measured in 491 samples which were obtained during steady 24 h infusions of the daily doses. Results were analyzed in four subgroups formed according to the postmenstrual ages of the patients at the time of blood withdrawal and showed good agreement with the reference values. Acute cholestasis was observed in 22 infants which could be explained by bacterial infection alone in 18 patients.

In 6 of 24 infants studied (27th-40th weeks of gestation), acquired and congenital structural anomalies of the airways were detected with an ultrathin flexible fiberscope (Olympus PF18 S, 1.8 mm). Introduction of the fiberscope via a modified four-way T-adapter enabled us to continue artificial ventilation without interrupting oxygen flow or positive pressure ventilation. Tube position, mucus accumulation and partial tube obstruction were determined quickly at the infants' bedside, when problems in artificial ventilation arose.