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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.

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.

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.

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.

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.

Aims The aim of this study was to investigate whether clinical and radiological outcomes after intramedullary nailing of displaced fractures of the fifth metacarpal neck using a single thick Kirschner wire (K-wire) are noninferior to those of technically more demanding fixation with two thinner dual wires. Patients and Methods This was a multicentre, parallel group, randomized controlled noninferiority trial conducted at 12 tertiary trauma centres in Germany. A total of 290 patients with acute displaced fractures of the fifth metacarpal neck were randomized to either intramedullary single-wire (n = 146) or dual-wire fixation (n = 144). The primary outcome was the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire six months after surgery, with a third of the minimal clinically important difference (MCID) used as the noninferiority threshold. Secondary outcomes were pain, health-related quality of life (EuroQol five-dimensional questionnaire (EQ-5D)), radiological measures, functional deficits, and complications. Results Overall, 151/290 of patients (52%) completed the six months of follow-up, leaving 83 patients in the single-wire group and 68 patients in the dual-wire group. In the modified intention-to-treat analysis set, mean DASH scores six months after surgery were 3.8 (sd 7.0) and 4.4 (sd 9.4), respectively. With multiple imputation (n = 288), mean DASH scores were estimated at 6.3 (sd 8.7) and 7.0 (sd 10.0). Upper (1 - 2α)) confidence limits consistently remained below the noninferiority margin of 3.0 points in the DASH instrument. While there was a statistically nonsignificant trend towards a higher rate of shortening and rotational malalignment in the single wire group, no statistically significant differences were observed across groups in any secondary outcome measure. Conclusion A single thick K-wire is sufficient for intramedullary fixation of acute displaced subcapital fractures of the fifth metacarpal neck. The less technically demanding single-wire technique produces noninferior clinical and radiological outcomes compared with the dual-wire approach. Cite this article: Bone Joint J 2019;101-B:1263–1271

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.

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.

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.

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.

Leptin is involved in the regulation of food intake and energy expenditure and is therefore important for growth and brain development. Analytical methods used for leptin measurement in human milk differ widely in the literature and yield varying results.To compare different preparation methods for the analysis of leptin in human milk and to investigate the leptin levels in colostrum and mature human milk from mothers of preterm or term infants.Mothers delivering a preterm (n=37) or a term infant (n=40) were recruited for a prospective study and were ask to collect breast milk on the 3rd and 28th day of lactation. Leptin, protein and fat concentrations were analysed. Clinical data of mother and child were recorded prospectively.Skim milk was most appropriate for leptin analysis. Human milk leptin concentrations did not differ between preterm and term human milk. In term milk, leptin concentration on day 28 was lower than on day 3 (p0.05). Milk leptin levels on the 3rd and 28th day were positively correlated with mothers' body mass index, but not with fat content in milk.Skim milk was the most stabile preparation for leptin analysis. Preterm and term human milk contain leptin in equal concentrations. Human milk leptin depends on mothers' body mass index.

Deformations have been attributed to supernatural causes since antiquity. Cerebral palsy was associated with God’s wrath, witchcraft, the evil eye, or maternal imagination. Greek scholars recommended prevention by tight swaddling, a custom that persisted into modern times. In the Middle Ages, the midwife’s negligence was held responsible as was difficult teething. Morgagni described in 1769 that the neonatal brain can liquefy, and Bednar described leukomalacia in 1850 as a distinct disorder of the newborn. In 1861, Little associated cerebral palsies with difficult or protracted labor and neonatal asphyxia, but he was challenged by Freud, who in 1897 declared that most cases are prenatal in origin. In 1868, Virchow demonstrated inflammatory changes, a view recently confirmed by Leviton and Nelson. Although a causal relationship of cerebral palsy to the birth never has been established, the habit to put the blame for cerebral palsy on someone remained a frequent attitude.

Patent ductus arteriosus (PDA) is a frequent problem in preterm infants, and its incidence is inversely correlated with gestational age. The efficacy of medical treatment decreases with decreasing gestational age (GA), and failure rates as well as ductus ligation rates of 40% have been reported in28 week GA newborns. The aim of this study was to determine whether echocardiographic parameters can predict response to ibuprofen treatment of PDA.In a longitudinal study, 29 infants born28 week GA were screened for a significant PDA (left atrial to aortic root ratio1.4, anterior cerebral artery resistance index0.8, and oxygen requirement35%) at 24-72 h of life and, if a PDA was found, treated with 10-5-5mg/kg ibuprofen intravenously every 24h. Ductal parameters were monitored by serial echocardiography. Infant neurodevelopmental outcomes were assessed at 24 month corrected age.All 15 infants with significant PDA responded to the ibuprofen loading dose indicated by reduced PDA diameters or increased PDA maximum flow velocities (PDA V(max)), and 7 patients showed an ongoing response resulting in a closed PDA after the 1st cycle (47%). Of the 8 non-responders, 7 received a 2nd cycle with 2 further responders (29%). All non-responders to the 2nd course had a PDA V(max)or=180 cm/s and increasing ductal diameters after the 3rd ibuprofen dose of the 1st course.Maximum flow velocity and diameter of the PDA at the end of the 1st cycle discriminate between responders and non-responders to further ibuprofen treatment.

Background Speech development is frequently impaired in very low birth weight (VLBW) infants. Few and controversial data have been published on concepts regarding the influence of bilingual education. Aims The objectives of the current study were to assess the influence of parental bilingualism on speech development and neurodevelopmental outcome in low risk VLBW infants. Study design Monocentric prospective controlled cohort study with standardized follow-up. Subjects We recruited 50 singleton VLBW infants each from monolingual and bilingual families as well as 90 term control infants. The infants were free of disease and congenital malformation. Outcome measures Griffiths scales of infant development at the corrected ages of 6 and 12 months, Bayley Scales of Infant Development II (BSID II) with 22 months. Results In general, both bilingual and monolingual VLBW infants achieved age-specific milestones at the corrected age of 6, 12 and 22 months. However, bilingual VLBW infants achieved significantly lower scores than their monolingual peers in all cognitive subscales. The influence of maternal education on the neurodevelopmental outcome of the preterm infants was not significant; the subscales' correlation with socioeconomic or biological parameters was poor. However, a clear differentiation between social status and bilingual environment importance for speech development was not possible. Conclusions In the setting of the present investigation, parental bilingualism is associated with slower neurodevelopment in VLBW infants during the first 2 years of life.

Growth of very low birthweight (VLBW) infants is used to monitor nutrition and intrauterine velocity is taken as the desired goal.We hypothesised that beside nutrition growth failure is caused by disease severity.Prospective longitudinal study of 45 VLBW infants undergoing intensive care, mechanical ventilation was used as proxy to disease severity. Nutritional intake, body weight, length, head circumference, and lower leg length (LLL) were measured during the first 5 weeks of life.Birthweight and gestational age were lower in 22 ventilated than in 23 unventilated infants (p0.01). Median daily intake was 3.2 and 2.8 g/kg for protein (n.s.), 108 and 112 kcal/kg for energy (n.s.), 175 and 160 ml/kg for volume (p0.01) up to day 35, respectively. Chronic lung disease occurred in 12 infants, five of whom were treated with dexamethasone. Artificial ventilation (p0.01) and dexamethasone treatment (p0.05) were independent predictors of weight gain. Median weight gain (8.2 and 9.7 g/kg/d), head growth (0.45 and 0.60 cm/week), and LLL growth (0.28 and 0.35 mm/d) were lower (p0.05) in ventilated than in non-ventilated infants, respectively. The correlation of LLL growth with body length (r=0.31, p0.05) and head growth (r=0.42, p0.01) was weak. Dexamethasone arrested growth; median LLL gain was 0.21 and 0.31 mm/d in ventilated infants with and without dexamethasone (p0.05).In VLBW infants, fetal growth rates are not reached with current feeding practice. In addition to inadequate nutrition, factors directly related to disease and treatment contribute to postnatal growth failure.

Prosodic information, such as word stress and speech rhythm, is important in language acquisition, and sensitivity to stress patterns is present from birth onwards. Exposure to prosodic properties of the native language occurs prenatally. Preterm birth and an associated lack of exposure to prosodic information are suspected to affect language acquisition in preterm infants. Fifty healthy very low birthweight (1500 g) preterm German infants (24 males, 26 females; mean gestational age [GA] 27.6 wks, range 26.4-29.9) and 103 comparison term infants (48 males, 55 females; mean GA 40 wks, range 39.4-40.8) were recruited. Prosodic discrimination performance was assessed using the head-turn preference paradigm, an objective behavioural psycholinguistic test for measuring orientation time (OT) to auditory stress patterns. Among matched preterm and term infants, preterm infants (n=30) did not differentiate stress patterns at the corrected age of 4 or 6 months. In term infants (n=30), the OT was longer towards the trochaic (stress on first syllable, characteristic for German) than the iambic (second syllable) stress patterns (11.64 vs 9.18s, p0.001, and 11.02 vs 8.32s, p0.001, at 4 and 6 mo respectively). Neurodevelopmental scores (Bayley Scales of Infant Development, 2nd edn) were not different from reference values in both groups of infants. Preterm birth and deficient early prosodic information affect prosodic processing during the first half year of life.

Aim: The mortality risk of very low birth weight (VLBW) (

Posthemorrhagic hydrocephalus (PHHC) represents a major complication of preterm birth. The aim of this study was to determine whether cerebrospinal fluid (CSF) levels of the pro-inflammatory cytokines IL-1beta, IL-18, and interferon (IFN)-gamma are altered in the CSF of preterm infants with PHHC and may serve as a marker of white matter damage (WMD). Twenty-seven preterm infants with PHHC were included in the study; 13 of them had signs of cystic WMD (cWMD) on ultrasound examinations. CSF sample 1 was obtained at first ventriculostomy, sample 2 at shunt implantation. Results were compared with a control group of 20 age-matched patients without neurologic diseases. IL-1beta concentrations were elevated in CSF sample 1 of PHHC patients without WMD and in sample 1 of patients with cWMD. Concentrations of IL-18 were increased in both samples of patients without WMD and in sample 2 of patients with cWMD. CSF levels of IFN-gamma were elevated in sample 1 of PHHC patients with cWMD. The pro-inflammatory cytokine IL-1beta and IL-18 levels in the CSF are elevated in patients with PHHC. Higher IFN-gamma levels are detected in a subgroup of patients developing cWMD, indicating its involvement in the pathogenesis of cWMD in the context of PHHC.

Objective: A prospective observational study to investigate hematologic alterations during the first 3 months of life in HIV-exposed uninfected infants subjected to antiretroviral medication before and after birth. Methods: Two hundred twenty-one consecutive uninfected infants born to HIV-positive mothers on antiretroviral medication during pregnancy were included. Perinatal transmission prophylaxis comprised zidovudine (ZDV) administered intravenously intrapartum and 10 days after birth. Blood counts and differentials were determined at birth and at 2, 4, 6, and 12 weeks of age, and hematologic toxicity was graded according to pediatric toxicity scales. Data were analyzed according to the kind of prenatal medication (ZDV alone or with another nucleoside reverse transcriptase inhibitor [NRTI] vs. highly active antiretroviral therapy [HAART]). Results: Median hemoglobin was significantly lower in HAART-exposed newborns from birth (P = 0.004) until day 28. During follow-up, 119 (53.8%) infants had anemia grade 2 or higher on at least 1 occasion; 16 (7.2%) received red blood cell transfusion at 23 (range: 1-56) days of age. Neutropenia grade 2 or higher occurred in 106 (48.0%) infants at least once; 8 infants had staphylococcal infections, and 2 infections were severe. After adjustment for possible confounders (prematurity, birth weight, ethnicity, gender, duration of maternal antiretroviral therapy, maternal Centers for Disease Control and Prevention stage, and maternal illicit drug use), HAART exposure was the only independent risk factor for anemia (odds ratio [OR] = 2.22, 95% confidence interval [CI]: 1.06 to 4.64; P = 0.034) and neutropenia (OR = 2.15, CI: 1.02 to 4.55; P = 0.045). Conclusions: Antiretroviral transmission prophylaxis is associated with significant anemia and neutropenia in HIV-uninfected infants during the first 3 months of life. Anemia was more profound in HAART-exposed infants.

We hypothesized that very low birth weight (VLBW) infants have reduced serum and red blood cell (RBC) selenium (Se) at birth, which decrease further with current nutrition and are associated with chronic lung disease and septicaemia.We studied Se intake, concentration in serum and RBCs and glutathione peroxidase (GSH-Px) activity in preterm and term infants from birth until 16 weeks. Data are mean+/-standard deviation (s.d.).Seventy-two preterm infants in two groups, born in Berlin, gestational age 26+0/30+0 weeks, birth weight 845/1270 g, with low Se intake (2.2+/-0.8/2.5+/-1.2 microg/kg/day), and 55 term infants, gestational age 39+1 weeks, birth weight 3160 g, born in Venezuela (high Se intake: 29+/-8 microg/day).A balance study in 10 preterm infants showed that Se is well absorbed from human milk (77+/-9%). Serum concentration was higher in term (142.0+/-40.0 microg/l) than in preterm infants (17.8+/-8.1/19.9+/-2.2 microg/l) at 4/7 weeks. Serum and RBC concentration of Se declined in all infants, low values in preterm infants did not correlate with chronic lung disease and septicaemia. GSH-Px activity in RBCs remained stable until 6 weeks of age in all infants and was not correlated with Se in RBCs.Se concentration in serum decreases during the first weeks of life and depends on intake. GSH-Px activity is not useful as a marker for Se status in infants up to 16 weeks after birth.

The aim of this prospective follow-up study was to evaluate the accuracy of a parent-completed questionnaire compared with professionally detected developmental delay. Parents of 108 very-low-birthweight (VLBW) infants and parents of 279 term control infants completed the German version of the Revised Prescreening Developmental Questionnaire (R-PDQ) at the corrected age of 12 months. Simultaneously, infants underwent developmental examination using the Griffiths Developmental Scale. Sixty-nine VLBW infants were classified as not delayed, 16 as delayed by both methods (conegativity 76% and copositivity 94%), as compared to 240 and six term control infants (conegativity 88%, copositivity 94%). The questionnaire suggested delay in 22 VLBW infants and 32 control infants, which was not substantiated by professional examination (P=0.006). In contrast, examination-diagnosed delay was missed by the questionnaire in one infant in each group. The R-PDQ is a reliable monitoring instrument for both VLBW and term infants at the age of 12 months. Parents of VLBW infants tend to underestimate their infants' development.

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.

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 µg/l in samples obtained on the first day of life (range 1.2–44.9 µg/l, median 6.8 µg/l). Peak S-100B in urine samples collected during the first 12 h of life were negatively related to gestational age (Rs = –0.882, p = 0.009). Three of the 8 preterm infants had peak urinary concentrations >10 µg/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.

Extremely low birthweight (1000 g) infants are growing rapidly and their nutritional requirements for calcium, phosphorus, magnesium are high.Prospective, mineral balance.The study was carried out at the Department of Neonatology, Virchow-Hospital, Charité Berlin and the Department of Molecular Trace Element Research, Hahn-Meitner-Institute Berlin.Nineteen infants1000 g birthweight were admitted, nine infants dropped out and 10 infants (birthweight 730-995 g), fed fortified human milk were included.We collected infant's urine and feces for 72 h, a sample of human milk and infant's blood at 7 and 12 weeks of age. Elements were measured by inductively coupled plasma atomic emission spectrophotometry.Mean (s.d.) mineral concentration in milk was low especially at 12 weeks: calcium 9.88 (+/-3.58) mmol/l, phosphorus 7.02 (+/-3.81) mmol/l, magnesium 1.59 (+/-0.54) mmol/l. Calcium retention was minimal or negative during the study, whereas phosphorus and magnesium balances were positive. Caffeine and diuretics increased mineral excretion. Serum alkaline phosphatase was mostly800 U/l, and 162 U/l in one infant with zinc deficiency at 12 weeks. Alkaline phosphatase correlated with absorption and retention of phosphorus, and with longitudinal growth.Infants1000 g have high nutritional needs for calcium, phosphorus and magnesium, which are not met by a human milk fortifier widely used in Europe. Controlled trials are needed to assess requirements, duration and risks of mineral supplementation.

Complement 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 duringin vitroECMO with repeated flow of the same blood volume was measured using blood from healthy adult donors. C3a increased significantlyin vivoafter 1 h (from 1035 ± 193 to 1865 ± 419 μg/l) andin vitroECMO (from 314 ± 75 to 1962 ± 1062 μg/l). C5a increased during ECMO without significant differences betweenin vivoandin vitroactivation. In neonatal patients, sC5b-9 rose faster thanin vitro, but the rapid increase was also significant forin vitroexperiments (in vivo: from 328 ± 63 to 1623 ± 387 μg/l after 2 h; andin vitro: from 78 ± 32 to 453 ± 179 μg/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.

Objective: Extremely low birth weight (ELBW) infants frequently undergo transfusion because they are critically ill, often need artificial ventilation, and have the highest blood sampling loss in relation to their weight. During the last decade our transfusion guidelines were changed 3 times to become more restrictive. We hypothesized that these modifications substantially decreased the number of transfusions in our ELBW infants. Methods: We performed a single-center analysis of 256 infants with birth weights from 500 to 999 g who were admitted from 1989 to 1997 and included 3 study periods, each starting with newly modified transfusion guidelines in April 1989, September 1991, and January 1995. We evaluated prospectively recorded clinical data and retrospective chart analysis for transfusion-related information. Results: The median number of transfusions per infant decreased from 7 in the first period to 2 in the third period, whereas donor exposure decreased from 5 to 1 and blood volume transfused decreased from 131 to 37 mL/kg birth weight (P < .01). The median venous hematocrit measured before transfusion decreased from 43% to 35% in infants who underwent ventilation and from 41% to 31% in spontaneously breathing infants. The median birth weight decreased from 870 to 740 g and the median gestational age from 27 to 25 completed weeks (P < .01). The overall survival rate was 75% and did not change. The incidences of retinopathy, intraventricular hemorrhage, and patent ductus arteriosus remained unchanged. Conclusion: Over this 9-year period with increasingly restrictive transfusion guidelines, the transfusion number decreased by 71% and the donor exposure by 80% in ELBW infants without adverse clinical effects. (J Pediatr 2000;136:220-4)

Nosocomial infection (NI) was prospectively studied in hospitalized neonates during a 10-month period. The Centers for Disease Control (CDC) criteria (some specified for neonates) were used for surveillance. Forty-nine of 677 infants experienced 73 episodes of NI. The overall incidence was 10.8 NI/100 patients and 6.5 NI/1,000 patient days. The average monthly NI number did not correlate with patient load. Very low birth weight (VLBW) infants showed a higher NI incidence (81.8 NI/100 patients and 11.1 NI/1,000 patient days), also elevated if adjusted for their inherently longer neonatal intensive care unit (NICU) stay. The most common NI sites in the VLBW stratum were sepsis and necrotizing enterocolitis (NEC), the latter occurring in a seasonal cluster. It can be concluded that surveillance for NIs should focus on VLBW infants and include the evaluation of NEC, as it behaves like a nosocomial disease.

We determined the influence of head position on lateral ventricular cerebral volume in low-birth-weight infants by three-dimensional (3-D) ultrasound (US). Thirty-nine neonates were examined prospectively in a controlled and blinded study. We used a freehand 3-D US system to acquire data sets after head positioning for 3 h on left and right side in random order. The borders of the lateral ventricles were marked in stored cross-sections. Volumes were calculated as mean of duplicate measurements. Median volume of lateral cerebral ventricles was 1.03 (quartiles 0.78-1.36) mL. Median left ventricular volume was slightly larger than right one (p = 0.13). Down-side lateral ventricles showed smaller volumes than up-side positioned ventricles (p0.01). Freehand 3-D US allows quantification of small volumes as neonatal lateral cerebral ventricles. Head position influences the lateral cerebral ventricle volume in low-birth-weight infants.

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.

We investigated thein vitroeffect of different form s of acidosis (pH 7.0) on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 μ mol/ml blood) or lactic acid (5.5 μ mol/ml) to heparin blood(N=12)caused significant activation of C3a and C5a compared to control (bothp=0.002). Respiratory acidosis activated C3a(p=0.007)and C5a(p=0.003)compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5.

Agenesis of the superior vena cava is a rare anomaly that is generally asymptomatic in the neonate. We report a male neonate with bilateral (total) agenesis of the superior vena cava with obstructed thoracic duct and subsequent congenital hydrothorax, anomalies that were detected by prenatal ultrasound at 25 weeks' gestation. The cardiac anomaly was confirmed by postnatal magnetic resonance angiography. The chylothorax disappeared with conservative therapy.

This article traces the decline of milk from a heavenly elixir to a tradeable food. Early cultures regarded milk not as a simple nutrient, but a living fluid. Heroes and gods were believed to have been nurtured by animals after being abandoned. Character traits were assumed to be transmitted by milk; infantile diseases were attributed to “bad milk”, whereas “good milk” was used as a remedy. With chemical methods developed at the end of the 18th century, it became known that human milk was higher in sugar and lower in protein than cow’s milk. During the 19th century, “scientific” feeding emerged that meant modifying cow’s milk to imitate the proportion of nutrients in human milk. In Boston from 1893, Rotch initiated the “percentage” method, requiring a physician’s prescription. In Paris from 1894, Budin sterilized bottled infant milk. In Berlin in 1898, Rubner measured oxygen and energy uptake by calorimetry, prompting feeding by calories, and Czerny introduced regulated feeding by the clock. These activities ignored the emotional dimension of infant nutrition and the anti-infective properties of human milk. They may have also enhanced the decline in breastfeeding, which reached an all-time low in 1971. Milk’s demystification made artificial nutrition safer, but paved the way for commercially produced infant formula.

Background: Within a longitudinal developmental surveillance project we tested the accuracy of the Revised Prescreening Developmental Questionnaire (R-PDQ) to detect developmental retardation in very low birthweight (VLBW) infants. Methods: Seventy surviving VLBW-infants born between July 1992 and December 1993 were re-examined at 6 months corrected age. The parent-completed questionnaires (n = 67) were compared with developmental assessment using the Griffiths Developmental Scale. Results: At 6 months corrected age, normal results on the Griffiths Developmental Scale (developmental quotient ≥ 81) were found in 61 67 (91%) VLBW-infants and in 45 67 (67%) questionnaires (no or one ‘delay’). The parents identified all six infants with psychomotor retardation on the Griffiths Developmental Scale (co-positivity 100%). However, only 45 61 infants with normal development were so identified with the R-PDQ (co-negativity 74%, positive predictive value 27%). Conclusions: The R-PDQ discovered all infants whose developmental quotient was two standard deviations below the mean on the Griffiths Developmental Scale. The relatively high proportion of false positive R-PDQ results corresponded to lower developmental quotients within the normal range. Therefore, the R-PDQ provides a useful screening instrument for VLBW-infants.

We report on a macrosomic newborn girl with albinism, a black lock at the right temporo-occipital region, and retinal depigmentation. Bilateral deafness was confirmed by brainstem auditory-evoked potentials. In addition, the infant had a severe defect of intestinal innervation. Biopsy showed aganglionosis of the large intestine, and total absence of neurocytes and nerve fibers in the small intestine, indicating a total lack of sympathetic and parasympathetic innervation. The infant died of intestinal dysfunction at 5 weeks. She was the 14th child of consanguineous Kurdish parents. Four sibs of our patient had the same syndrome and died a few days after birth. The other 9 sibs are well, with an unremarkable phenotype. A syndrome of albinism, black lock, deafness, and a total lack of intestinal neural innervation has not yet been reported. It represents a new neural crest syndrome with autosomal-recessive inheritance. © Wiley-Liss, Inc.

Background: Vascular endothelial growth factor (VEGF) and its receptors regulate angiogenesis (formation of blood vessels). The soluble VEGF receptor 1 (sFlt-1) binds VEGF as a potent antagonist. Objective: The objective of this study was to compare VEGF and sFlt-1 levels in milk from mothers of preterm (n = 50) versus term (n = 49) infants in a longitudinal study. Methods: Milk samples were collected on days 3 and 28 of lactation. Vascular endothelial growth factor and sFlt-1 were quantified by sandwich-type enzyme-linked immunosorbent assay. Results: Vascular endothelial growth factor and sFlt-1 were found in high concentrations in early milk (lactation day 3) from mothers of preterm and term infants and were lower in mature milk (lactation day 28). On day 3, median VEGF concentration was lower in preterm than in term milk (37.1 vs 53.9 ng/mL, P < .01). Otherwise, VEGF (day 28) and sFlt-1 (days 3 and 28) did not differ in preterm versus term milk. Conclusions: It was shown for the first time that sFlt-1 is present in human milk. Early human milk contains high concentrations of VEGF and sFlt-1, which decrease over the course of lactation.

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.

The leukocyte glycoprotein l-selectin mediates an early step in the recruitment of leukocytes to sites of inflammation. l-Selectin surface expression is rapidly down-regulated by inflammatory signals in vitro. In a prospective study, we found l-selectin expression on umbilical cord blood granulocytes and monocytes to be significantly decreased in newborn infants with acute bacterial infection compared with controls (p < 0.01). A significantly reduced l-selectin expression of both granulocytes and monocytes was also found to be associated with an increased neutrophil immature/total ratio (p < 0.01) but not with other laboratory markers of neonatal sepsis. There was no apparent impact of prematurity, low birth weight, gestational hypertension, or gestational diabetes on l-selectin expression. Although the mode of delivery did not affect granulocyte l-selectin expression, umbilical cord blood monocytes showed an increased l-selectin expression after emergency cesarean delivery compared with samples obtained after elective cesarean or vaginal delivery (p < 0.01). We conclude that acute systemic inflammation results in down-regulation of granulocyte and monocyte l-selectin expression in vivo similar to that observed in vitro.

A method for continuous monitoring and recording of neonatal heart rate variability (HRV) and further physiological parameters in the intensive care unit is presented: 16 neonatal monitors were connected via two input/output processor boards to a personal computer. Patient data were processed by special software. Every day a 24-h record was printed for each infant, including a continuous registration of long-term (LTV) and short-term variability (STV) of heart rate along with baseline heart rate, respiratory rate, body temperature, temperature of the incubator and transcutaneous partial pressures of oxygen and carbon dioxide (tcPO2 and tcPCO2). For each parameter automatic artefact removal was implemented. Median and percentiles were computed once daily from all valid values. The influence of gestational and postnatal age and of respiratory distress syndrome (RDS) on HRV was studied in 105 preterm infants below 33 weeks of gestation during the first 7 days of life. An increase of both LTV and STV was seen with increasing gestational and postnatal age. In infants with RDS a decreased LTV was found in relation to the severity of the disease. HRV was also decreased in impaired brain function due to intraventricular hemorrhage, asphyxia or sedative treatment.

In preterm newborn infants, topical iodine-containing antiseptics disturb thyroid hormone regulation while alcohol-based disinfectants may cause local burns. We therefore investigated the use of an aqueous solution containing 0.1% octenidine and 2% 2-phenoxyethanol for skin disinfection during the first seven days of life in premature newborns with a gestational age

Survivors of immaturity of outstanding intelligence include Fortunio Licetus, born in 1577, and Isaac Newton, born in 1643. Reliable descriptions began appearing around 1820, and over a dozen infants were born weighing under 1000 g and before World War II, who developed normally. From 1876 to 2006, the birth weight at which half of the infants survived dropped from 2200 to 600 g. Statistics depended on how abortion, stillbirth and live birth were defined, which differed greatly from country to country. WHO definitions in 1993 required the registration of all infants weighing 500 g (22 complete weeks) or above. This definition was not universally adopted, resulting in considerable underreporting. Many medical societies issued ethical recommendations concerning the obligatory or optional treatment of immature infants. The "window", at which treatment is optional has been set at 22-23 weeks (Japan, Germany), 23-24 weeks (UK, USA, Canada), or 24-26 weeks (France, Netherlands, Switzerland). Instead of assessing an infant's individual prognosis, and ignoring its gender, co-morbidities, and particular cause of premature delivery, these rules frequently relied on gestational age alone to initiate or withhold life support.

The interest in the limit of viability originated from various sources, including legal requirements, the rejection of mechnical life support, competition for resources, concerns about handicaps, and proximity to the fetus with its limited rights. Gestational age was determined from menstrual history by Hippocratic writers, who established the tenacious idea that 7-, but not 8-month infants could survive. Naegele's rule, already published by Boerhaave in 1744, was correct when applied to the last day of menstruation. Birth weight and length were not measured until the end of the 18(th) century. This remarkable disinterest resulted from superstition, grossly inaccurate measurements by the authorities Mauriceau and Smellie, and the conversion chaos of the pre-metric era. A table is provided with historic mass and length units allowing to determine birth weight and body length in the older literature. The idea of viability is a remnant of vitalism, a medical doctrine popularized in 1780 by Brown. Many short-lived statements defined its limit, but until now what was meant by viability remained nebulous.

A human being born without heart and head, i.e., the acardius/acranius malformation, has been described since antiquity. Superstition and fear made it a mystical disorder, a sign of God's wrath. The inquisition ruled that acranic infants should not be baptized and located the soul in the brain. Acardia was not associated with twin gestation until the reports of Mery in 1720 and Winslow in 1740. In 1850, Meckel identified the pathogenetic mechanism as reversed perfusion due to large arterio-arterial and veno-venous anastomoses; he believed the heart would fail to develop or arrest during development, and the acardiac fetus would be maintained by arterial perfusion from the pump twin. In 1859, Claudius articulated that after normal initial development, the heart degenerates when reversed flow in the aorta leads to thrombosis. Today, it is assumed that both mechanisms may exist. With the advent of prenatal ultrasound diagnosis and radiofrequency ablation of the acardiac twin's circulation, it became possible to save the pump twin.

Twin-twin transfusion is the major cause of mortality and morbidity in monochorionic twins. Its pathogenesis has been gradually elucidated over the last three centuries. Among obstetricians, there was a long-lasting controversy on the existence of placental anastomoses and whether or not to tie the placental end of the firstborn infant's cord. However, a twin pregnancy practically never could be excluded. Stalpart van der Wiel described a twin-twin vessel connection in 1687. Studies on interfetal anastomoses using injection of placental vessels were published by Smellie in 1752, Osiander in 1781, and Brachet in 1821. Different types of anastomoses, and their associated fetal disorders were classified by Schatz in a series of papers at the end of the 19(th) century. With the advent of ultrasound and laser techniques, prenatal diagnosis and treatment became available in the last decade of the 20(th) century.

A meta-analysis was performed of 9 controlled trials of maternal beta-/dexamethasone treatment in which the incidence of RDS in infants born before 30 weeks gestation was reported. A significant decrease could be shown in 250 immature infants. The number of cases was to small for analysis of lower gestational ages or for the demonstration of a reduction in mortality. In a separate study of 135 infants born before 30 weeks gestation tracheal aspirate phospholipid analysis was performed using thin layer chromatography. 64 of them had been exposed prenatally to steroids. Significantly more of these infants had a mature L/S ratio > or = 2.7 (p < 0.02) and prenatal glucocorticoid treatment was associated with a markedly increased survival rate (odds ratio 2.4, p < 0.02). We conclude from the meta-analysis of the literature and from the findings of our study, that accelerated lung maturation follows prenatal steroid treatment with a reduction in RDS-incidence even in very immature fetuses. Consequently it would be appropriate to administer glucocorticoids combined with tocolysis since this has been shown to be beneficial for those women threatening to deliver prematurely at less than 30 weeks gestation.

We report on a premature newborn girl delivered after 32 weeks of gestation by cesarean section after sparse limb movements, fetal tachycardia and late heart rate decelerations had suggested fetal distress. Following 1 day of mechanical ventilation, adequate pulmonary gas exchange was achieved by spontaneous breathing. Main symptoms were virtually complete absence of spontaneous movements, increased flexor tonus of the extremities, and hypotonia of the trunk. Inability to suck or swallow required nasogastric gavage feeding. There were no hypoglycemic episodes. Echocardiography revealed normal myocardial function. Creatine kinase was 237 U/I at 2 days of life, declining to normal values thereafter. Muscle biopsy revealed increased glycogen storage with subsarcolemmal glycogen deposits and low phosphorylase-a activity while total phosphorylase was normal after in vitro activation, suggestive of phosphorylase-b kinase deficiency. No mutation was detected in exon 1 of the myophosphorylase gene. No psychomotor development was observed, and the infant died of central apnea at 3 months of age.

Aim To compare neurodevelopmental results in very low birth weight (VLBW) infants two years after successful or failed cyclooxygenase inhibitor treatment with either indomethacin or ibuprofen for a haemodynamically significant patent ductus arteriosus (hsPDA). Methods We retrospectively evaluated closure rates and outcome parameters of VLBW infants with hsPDA 89 of whom were treated with indomethacin and 93 with ibuprofen. Results Indomethacin and ibuprofen therapy groups did not differ in their baseline clinical profile (median gestational age 26.0 and 26.2 wks d) in early (median CRIB 6 and 5, respiratory distress > 2° in 36 and 34 infants) and late morbidities (intraventricular hemorrhage > 2° in 9 and 10 infants, bronchopulmonary dysplasia in 31 and 27 infants, 80 and 85 survivors), PDA closure rates (63 and 58%) or neurodevelopmental outcome. The therapy failure group (54 infants) was characterized by lower median gestational age (25.0 wks d) and higher mortality (17%). No differences were found in the neurodevelopmental outcome of the surviving infants with ligation as compared to the survivors with successful pharmacological closure of the PDA at 24 months corrected age. Conclusion Use of either ibuprofen or indomethacin for closure of a hsPDA did not influence two year neurodevelopmental outcomes in VLBW infants.

Vitamin A (VA) deficiency in very low birth weight (VLBW) infants is associated with an increased risk for disorders related to kidney and lung maturation and function. VA losses through increased urinary retinol (ROH) excretion might contribute to this deficiency risk. The mechanism accounting for ROH loss in the urine has not yet been clarified. The aim of this study was to assess the excretion of ROH, retinol-binding protein 4 (RBP4) and transthyretin (TTR) in urine from VLBW infants in comparison with that in term infants in relation to kidney function. Urine specimens were collected from 15 VLBW infants (birth weight < 1,500 g) as well as from 20 term infants during the first 2 days after birth. ROH in urine was detectable in 14 of the 15 VLBW infants at a median concentration of 234 nmol/g creatinine. In the group of term infants, 17 of the 20 excreted ROH, but at an approximately five-times lower concentration (P < 0.001). Excretion of RBP4 and TTR was also much higher in VLBW infants (both P< 0.001). The urinary ROH excretion in VLBW infants may be related to the impaired tubular handling of its carrier proteins RBP4 and TTR. Thus, ROH excretion might contribute to an increased risk of VA deficiency, especially in VLBW infants.

Aim: To determine whether ibuprofen use in VLBW infants is associated with increased serum bilirubin levels and impaired neurodevelopmental outcome at 2 years of age compared to indomethacin. Methods: We retrospectively evaluated bilirubin data and outcome parameters of 178 VLBW infants treated with COX inhibitors for a haemodynamically relevant patent ductus arteriosus (PDA) between 1998 and 2003 in a single institution. In our department ibuprofen replaced indomethacin for PDA treatment in 2001, while clinical and echocardiagraphic criteria for the indication of PDA invention have remained unchanged. Results: Ibuprofen and indomethacin therapy groups did not differ in their baseline clinical profile. Peak serum bilirubin concentration was 10.2 mg/dL in the ibuprofen group and 8.6 mg/dL in the indomethacin group (p < 0.01), while phototherapy duration did not differ. At 2 years of age neurodevelopmental outcome was similar in both groups. In a single case analysis, four cases of adverse neurodevelopmental outcome despite inconspicuous clinical course were identified in the ibuprofen group. Conclusion: In VLBW infants with PDA, ibuprofen treatment was associated with higher bilirubin levels than indomethacin.

Aim: Intraventricular haemorrhage (IVH) causes some of the most adverse outcomes in infants with birthweight