For Exposed and Deserted Young Children: Research at the London Foundling Hospital.

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.

Neonatal Research at the Archiospedale Santo Spirito in Rome.

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.

From Exclusion to Glass Ceiling: A History of Women in Neonatal Medicine.

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.

Exposed and Abandoned. Origins of the Foundling Hospital.

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.

Dishonoured: The Fate of Infants Born out of Wedlock.

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.

Ignored Papers, Invented Quotations: A History of Fetal Alcohol Syndrome.

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.

Swinging and Rocking: Two Millennia of Debating the Cradle.

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.

Revived for Paradise: A History of Respite Sanctuaries.

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.

Pulmo uterinus: a history of ideas on fetal respiration.

Theories about fetal respiration began in antiquity. Aristotle characterized pneuma as warm air, but also as the enabler of vital functions and instrument of the soul. In Galen's system of physiology, the vital spirit was carried by the umbilical arteries, the nutrients by the umbilical vein from the placenta to the fetus. In 1569 Aranzio postulated that the maternal and fetal vasculatures are distinct. From 1670 to 1690, a century before the discovery of oxygen, researchers understood that during respiration some form of exchange with the air must occur, naming the substance biolychnium, phlogiston, sal-nitro, or nitro-aerial particles. An analogy of placental and pulmonary gas exchange was described in 1674 by Mayow. In 1779, Lavoisier understood the discovery of oxygen, discarded the phlogiston theory, and based respiration physiology on gas exchange. With the invention of the spectroscope, it became possible to measure hemoglobin oxygenation, and in 1876 Zweifel proved fetal oxygen uptake. Major progress in understanding fetal gas exchange was achieved in the 20th century by the physiologists Barcroft in Cambridge and Dawes in Oxford.

Animatio: a history of ideas on the beginning of personhood.

The onset of individual human life has fascinated thinkers of all cultures and epochs, and the history of their ideas may enlighten an unsettled debate. Aristotle attributed three different souls to the subsequent developmental stages. The last, the rational soul, was associated with the formed fetus, and entailed fetal movements. With some modifications, the concept of delayed ensoulment - at 30, 42, 60, or 90 days after conception - was adopted by several Christian Church Fathers and remained valid throughout the Middle Ages. The concept of immediate ensoulment at fertilization originated in the 15th century and became Catholic dogma in 1869. During the Enlightenment, philosophers began to replace the rational soul with the term personhood, basing the latter on self-consciousness. Biological reality suggests that personhood accrues slowly, not at a specific date during gestation. Requirements for personhood are present in the embryo, but not in the preembryo before implantation: anatomic substrate; no more totipotent cells; decreased rate of spontaneous loss. However, biological facts alone cannot determine the embryo's moral status. Societies must negotiate and decide the degree of protection of unborn humans. In the 21st century, fertilization, implantation, extrauterine viability and birth have become the most widely accepted landmarks of change in ontological status.

Cot Death: History of an Iatrogenic Disaster.

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.

From "apparent death" to "birth asphyxia": a history of blame.

Since the sixteenth century, competition between midwives and surgeons has created a culture of blame around the difficult delivery. In the late seventeenth century, 100 years before oxygen was discovered, researchers associated "apparent death of the newborn" with impaired respiratory function of the placenta. The diagnosis "birth asphyxia" replaced the term "apparent death of the newborn" during the mass phobia of being buried alive in the eighteenth century. This shifted the interpretation from unavoidable fate to a preventable condition. Although the semantic inaccuracy ("pulselessness") was debated, "asphyxia" was not scientifically defined until 1992. From 1792 the diagnosis was based on a lack of oxygen. "Blue" and "white" asphyxia were perceived as different disorders in the eighteenth, and as different grades of the same disorder in the nineteenth century. In 1862, William Little linked birth asphyxia with cerebral palsy, and although never confirmed, his hypothesis was accepted by scientists and the public. Fetal well-being was assessed by auscultating heart beats since 1822, and continuous electronic fetal monitoring was introduced in the 1960s without scientific assessment. It neither diminished the incidence of birth asphyxia nor of cerebral palsy, but rather raised the rate of cesarean sections and litigation against obstetricians and midwives.

Social Birth: Rites of Passage for the Newborn.

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.

Hepar uterinum: a history of ideas on fetal nutrition.

The means of fetal nutrition has been debated for over two millennia, with the controversy of oral versus parenteral nutrition already in the Corpus Hippocraticum. In 1587 Aranzio rejected connections between maternal and fetal blood vessels, and coined the term "hepar uterinum" for the placenta. From the 16th to the 18th century, a fervent debate focused on the type and extent of connection between maternal and fetal vessels, which was finally settled by Hunter's injection experiment in 1774. But up to the middle of the 19th century, an important nutritive function was attributed to amniotic fluid. When with the discovery of oxygen the placenta's respiratory function became understood, its nutritional function fell from grace. Most scientists realized reluctantly that the organ had numerous functions. As late as in the 19th century, the advent of microscopy allowed cell theory to develop, and analytical chemistry furthered the understanding of the transport of nutrients across the placenta. The identification of the syncytiotrophoblast made passive diffusion unlikely. Radioisotopes, molecular biology and the fluid mosaic model of the cell membrane revealed active transport mechanisms for nearly all macronutrients.

From Crime to Disease: Laws on Infanticide in the Modern Era.

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.

From Sin to Crime: Laws on Infanticide in the Middle Ages.

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.

Lethal Lullabies: A History of Opium Use in Infants.

Poppy extract accompanied the human infant for more than 3 millenia. Motives for its use included excessive crying, suspected pain, and diarrhea. In antiquity, infantile sleeplessness was regarded as a disease. When treatment with opium was recommended by Galen, Rhazes, and Avicenna, baby sedation made its way into early medical treatises and pediatric instructions. Dabbing maternal nipples with bitter substances and drugging the infant with opium were used to hasten weaning. A freerider of gum lancing, opiates joined the treatment of difficult teething in the 17th century. Foundling hospitals and wet-nurses used them extensively. With industrialization, private use was rampant among the working class. In German-speaking countries, poppy extracts were administered in soups and pacifiers. In English-speaking countries, proprietary drugs containing opium were marketed under names such as soothers, nostrums, anodynes, cordials, preservatives, and specifics and sold at the doorstep or in grocery stores. Opium's toxicity for infants was common knowledge; thousands of cases of lethal intoxication had been reported from antiquity. What is remarkable is that the willingness to use it in infants persisted and that physicians continued to prescribe it for babies. Unregulated trade, and even that protected by governments, led to greatly increased private use of opiates during the 19th century. Intoxication became a significant factor in infant mortality. As late as 1912, the International Hague Convention forced governments to implement legislation that effectively curtailed access to opium and broke the dangerous habit of sedating infants.

From Right to Sin: Laws on Infanticide in Antiquity.

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.