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 developpement 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

Complement activation by in vivo neonatal and in vitro extracorporeal membrane oxygenation.

Complment activation during extracorporeal membrane oxygenation (ECMO) in newborns can be caused by both the underlying disease processes and by blood contact with the ECMO circuit. We investigated the relative importance of these mechanisms by measuring C3a, C5a and sC5b-9 before, during and after neonatal ECMO in six consecutive newborn patients using enzyme-linked immunoassay. In addition complement activation during in vitro ECMO with repeated flow of the same blood volume was measured using blood from healthy adult donors. C3a increased significantly in vivo after 1 h (from 1035+/-193 to 1865+/-419 microg/l) and in vitro ECMO (from 314+/-75 to 1962+/-1062 microg/l). C5a increased during ECMO without significant differences between in vivo and in vitro activation. In neonatal patients, sC5b-9 rose faster than in vitro, but the rapid increase was also significant for in vitro experiments (in vivo: from 328+/-63 to 1623+/-387 microg/l after 2 h; and in vitro: from 78+/-32 to 453+/-179 microg/l after 8 h). After this initial peak at 1-2 h, complement activation decreased gradually until 2-3 days after the initiation of ECMO. We conclude that in newborns the rapid activation of the complement system after the start of ECMO is predominantly caused by contact with artificial surfaces rather than the patient's underlying disease

Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of children with hydrocephalus

BACKGROUND: Elevated intracranial pressure (ICP) resulting from impaired drainage of cerebrospinal fluid (CSF) causes hydrocephalus with damage to the central nervous system. Clinical symptoms of elevated intracranial pressure (ICP) in infants may be difficult to diagnose, leading to delayed treatment by shunt placement. Until now, no biochemical marker of elevated ICP has been available for clinical diagnosis and monitoring. In experimental animal models, nerve growth factor (NGF) and neurotrophin-3 (NT-3) have been shown to be produced by glial cells as an adaptive response to hypoxia. We investigated whether concentrations of NGF and NT-3 are increased in the CSF of children with hydrocephalus. METHODS: NGF was determined in CSF samples collected from 42 hydrocephalic children on 65 occasions (taps or shunt placement surgery). CSF samples obtained by lumbar puncture from 22 children with suspected, but unconfirmed bacterial infection served as controls. Analysis was performed using ELISA techniques. RESULTS: NGF concentrations in hydrocephalic children were over 50-fold increased compared to controls (median 225 vs 4 pg/mL, p < 0.0001). NT-3 was detectable (> 1 pg/mL) in 14/31 hydrocephalus samples at 2–51 pg/mL but in none of 11 control samples (p = 0.007). CONCLUSION: NGF and NT-3 concentrations are increased in children with hydrocephalus. This may represent an adaptive response of the brain to elevated ICP

Preconceptional factors associated with very low birthweight delivery in East and West Berlin: a case control study

BACKGROUND: Very low birthweight, i.e. a birthweight < 1500 g, is among the strongest determinants of infant mortality and childhood morbidity. To develop primary prevention approaches to VLBW birth and its sequelae, information is needed on the causes of preterm birth, their personal and social antecedents, and on conditions associated with very low birthweight. Despite the growing body of evidence linking sociodemographic variables with preterm delivery, little is known as to how this may be extrapolated to the risk of very low birthweight. METHODS: In 1992, two years after the German unification, we started to recruit two cohorts of very low birthweight infants and controls in East and West Berlin for a long-term neurodevelopmental study. The present analysis was undertaken to compare potential preconceptional risk factors for very low birthweight delivery in a case-control design including 166 mothers (82 East vs. 84 West Berlin) with very low birthweight delivery and 341 control mothers (166 East vs. 175 West). RESULTS: Multivariate logistic regression analysis was used to assess the effects of various dichotomous parental covariates and their interaction with living in East or West Berlin. After backward variable selection, short maternal school education, maternal unemployment, single-room apartment, smoking, previous preterm delivery, and fetal loss emerged as significant main effect variables, together with living in West Berlin as positive effect modificator for single-mother status. CONCLUSION: Very low birthweight has been differentially associated with obstetrical history and indicators of maternal socioeconomic status in East and West Berlin. The ranking of these risk factors is under the influence of the political framework

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

Surfactant bolus instillation: effects of different doses on blood pressure and cerebral blood flow velocities

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

Increased cerebral blood flow velocities in newborn infants of smoking mothers

Cerebral blood flow velocities (CBFV) were measured by the pulsed Doppler method in 41 infants of smoking mothers and in 59 apparently healthy control infants. Although gestational age, birth weight, and systolic blood pressure were lower in infants exposed to tobacco smoke prenatally, systolic (65 +/- 11 vs. 47 +/- 12 cm/s, mean +/- SD; P < 0.001), mean (36 +/- 6 vs. 25 +/- 6 cm/s; P < 0.001), and diastolic (17 +/- 4 vs 13 +/- 4 cm/s; P < 0.001) CBFVs in the anterior cerebral artery were significantly higher when compared to control infants. Similar differences were seen in the internal carotid and in the basilar arteries. Multiple regression analysis did not reveal differences other than maternal smoking to explain these observations. We conclude that prenatal tobacco smoke exposure is related to increased CBFVs in newborn infants. Further studies should determine whether this relation is not only statistical but causal and whether increased CBFVs are an indicator of prolonged effects of prenatal tobacco smoke exposure

Surfactantsubstitution beim sehr kleinen Frühgeborenen= Surfactant substitution in very small premature infants

In addition to the established treatment of neonatal respiratory distress syndrome by oxygen supplementation, artificial ventilation and thermoneutrality, substitution of surfactant offers a new therapeutic perspective. Up to now, either artificial mixtures of surface active components or surfactant extracts from minced animal lungs, lung lavage fluid, or human amniotic fluid have been used in controlled trials of prophylactic and rescue surfactant treatment. Meta-analysis of controlled prevention trials including about 2,400 preterm infants shows decreased mortality (21% in controls, 9.5% in infants treated with natural preparations, p less than 0.001; 17% in controls, 11% in infants treated with artificial preparations, p less than 0.001) and fewer complications of artificial ventilation (pneumothorax: 24 vs. 7.2% with natural preparations, p less than 0.001; 20 vs. 15% with artificial preparations, p less than 0.05). In rescue studies on more than 1,900 preterm infants, natural surfactant preparations decreased complications of artificial ventilation such as pulmonary interstitial emphysema and pneumothorax (32 vs. 13%, p less than 0.001). Although the immediate effect of artificial preparations is mild, the incidence of pneumothorax also could be reduced (30 vs. 19%, p less than 0.001). Mortality could be reduced by 1/3 with natural (31 vs. 20%, p less than 0.001) and with artificial preparations (23 vs. 16%, p less than 0.01). The incidence of bronchopulmonary dysplasia and intracerebral hemorrhage, however, did not drop significantly. Severe adverse side effects of this treatment seem to be rare. There are, however, potential hazards of surfactant substitution. Its use should be restricted to fully staffed and equipped neonatal intensive care units

Surfactant protein A in the course of respiratory distress syndrome

Surfactant-associated protein (SP-A) was measured in tracheal aspirates of ventilated infants with (n = 51) and without (n = 21) respiratory distress syndrome (RDS). SP-A concentrations in samples collected after birth were significantly lower in RDS than in infants ventilated for other reasons than RDS (median 0.03 vs. 1.60 micrograms/ml). As a biochemical test to diagnose RDS early after birth, the sensitivity of measuring SP-A in tracheal aspirates was 87% and specificity 81%. SP-A content in tracheal aspirates of infants with RDS was monitored during the first 7 days of life. A significant (P less than 0.001) increase within the first 4 days was found in those infants who survived, whereas no such change was found in those infants who died

Round table discussion.Future programs in the basic and clinical sciences on surfactant Stimulation and substitution

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