Costantino Romagnoli

Safety and Efficacy of Galactogogues: Substances that Induce, Maintain and Increase Breast Milk Production

Poor production of breast milk is the most frequent cause of breast lactation failure. Often, physician prescribe medications or other substances to solve this problem. The use of galactogogues should be limited to those situations in which reduced milk production from treatable causes has been excluded. One of the most frequent indication for the use of galactogogues is the diminution of milk production in mothers using indirect lactation, particularly in the case of preterm birth. The objective of this review is to analyze to the literature relating to the principal drugs used as galactogogues (metoclopramide, domperidone, chlorpromazine, sulpiride, oxytocin, growth hormone, thyrotrophin releasing hormone, medroxyprogesterone). Have been also analyzed galactogogues based on herbs and other natural substances (fenugreek, galega and milk thistle). We have evaluated their mechanism of action, transfer to maternal milk, effectiveness and potential side effects for mother and infant, suggested doses for galactogogic effect, and recommendation for breastfeeding.

Prophylactic ibuprofen therapy of patent ductus arteriosus in preterm infants.

Abstract This study was aimed at evaluating the efficacy of ibuprofen in the prophylaxis of patent ductus arteriosus (PDA) in very preterm neonates and at detecting eventual side-effects. A total of 46 preterm neonates with gestational age under 31 weeks were randomly assigned at 2 h of life: 23 to the prophylaxis group and 23 to the control group. The prophylaxis group received intravenous treatment with ibuprofen lysine (10 mg/kg), followed by 5 mg/kg after 24 h and 48 h. No placebo was given to the control group. No PDA was demonstrated at 72 h of life in 20 of the 23 babies in the ibuprofen group (87%) nor in 7 of the 23 control neonates (30.4%). All neonates with PDA received treatment with indomethacin. One neonate in the prophylaxis group and three in the control group underwent surgical ligation. Prophylaxis with ibuprofen was not associated with any significant side-effect except for food intolerance. Conclusion Ibuprofen prophylaxis seems to be efficient in closing patent ductus arteriosus and in reducing indomethacin treatment. No significant early side-effects were found due to ibuprofen.

The Surprising Composition of the Salivary Proteome of Preterm Human Newborn

Saliva is a body fluid of a unique composition devoted to protect the mouth cavity and the digestive tract. Our high performance liquid chromatography (HPLC)-electrospray ionization-MS analysis of the acidic soluble fraction of saliva from preterm human newborn surprisingly revealed more than 40 protein masses often undetected in adult saliva. We were able to identify the following proteins: stefin A and stefin B, S100A7 (two isoforms), S100A8, S100A9 (four isoforms), S100A11, S100A12, small proline-rich protein 3 (two isoforms), lysozyme C, thymosins β4 and β10, antileukoproteinase, histone H1c, and α and γ globins. The average mass value reported in international data banks was often incongruent with our experimental results mostly because of post-translational modifications of the proteins, e.g. acetylation of the N-terminal residue. A quantitative label-free MS analysis showed protein levels altered in relation to the postconceptional age and suggested coordinate and hierarchical functions for these proteins during development. In summary, this study shows for the first time that analysis of these proteins in saliva of preterm newborns might represent a noninvasive way to obtain precious information of the molecular mechanisms of development of human fetal oral structures.

Is serum Troponin T a useful marker of myocardial damage in newborn infants with perinatal asphyxia

Aim: To assess the correlation of echocardiographic signs of myocardial damage to serum cardiac troponin T (cTnT) concentrations in newborn infants with perinatal asphyxia.

A three year follow up of preterm infants after moderately early treatment with dexamethasone

Objective: To assess the effect of moderately early postnatal dexamethasone treatment on growth and neurodevelopmental outcome in preterm infants. Methods: Thirty preterm infants enrolled in a randomised clinical trial to investigate the effectiveness of moderately early dexamethasone administration in the treatment of chronic lung disease were routinely followed up. Fifteen babies received a total dose of 4.75 mg/kg over 14 days from the 10th day of life, and 15 babies were untreated. Five infants in each group received open label steroids to facilitate extubation later in their clinical course. Growth and neurodevelopmental outcome are reported. Results: The mean body weight, height, and head circumference as well as the number of babies with anthropometric measurements within normal range were similar in treated and untreated babies. There was no significant difference between treated and control groups with respect to incidence of cerebral palsy, major neurosensory impairment, mean intelligence quotient scores, and behavioural abnormalities. Conclusions: Postnatal dexamethasone treatment with the schedule used in this study did not impair growth and neurodevelopmental outcome in preterm infants. Data from larger trials have raised major concern that postnatal steroid treatment may increase neurodevelopmental impairment. The full extent of the risk will only be known when more trials have reported follow up data.

Skin bilirubin nomogram for the first 96 h of life in a European normal healthy newborn population, obtained with multiwavelength transcutaneous bilirubinometry

Aim: Hour‐specific nomogram evaluation of serum or skin bilirubin is a suitable approach for managing neonatal hyperbilirubinemia and it is recommended by American Academy of Paediatrics. We aimed to provide data about skin bilirubin levels during the natural course of hyperbilirubinemia in European healthy neonates.

Neonatal outcome in hypertensive disorders of pregnancy.

BACKGROUND Hypertensive disorders in pregnancy account for increased perinatal morbidity and mortality when compared to uneventful gestations. AIMS To analyze perinatal outcome of pregnancies complicated by different kinds of hypertension to uncomplicated pregnancies in a series of Italian women and to compare our data with series from other countries. STUDY DESIGN The sample was divided into four groups of hypertensive women: chronic hypertension (CH), gestational hypertension (GH), preeclampsia (PE), and chronic hypertension complicated by preeclampsia (CHPE). One thousand normal pregnancies served as controls. SUBJECTS Neonatal features of the offspring of 965 Italian women with hypertension in pregnancy were evaluated. MEASURES Gestational age, birthweight and the rate of small for gestational age were the outcomes. Perinatal asphyxia and mortality were also assessed. RESULTS Gestational age, the mean of birth weight and birth percentile were significantly lower in all groups with hypertensive complications when compared with controls. The rate of very early preterm delivery (<32 weeks) was 7.8% in CH, 5.9% in GH, 21.2% in PE and 37.2% in CHPE while it was to 1.2% in the control group. The rate of SGA was globally 16.2% in CH, 22.8% in GH, 50.7% in PE, 37.2% in CHPE and 5% in controls. The rate of SGA in PE was much higher than reported in series from other countries. CONCLUSION Comparing our data with those reported from other countries, it is evident that the rate of fetal growth restriction in PE we found in our center, is significantly higher even in the presence of a global lower incidence of PE.

Thymosin β4 and β10 Levels in Pre-Term Newborn Oral Cavity and Foetal Salivary Glands Evidence a Switch of Secretion during Foetal Development

Background Thymosin β4, its sulfoxide, and thymosin β10 were detected in whole saliva of human pre-term newborns by reversed-phase high performance chromatography coupled to electrospray ion-trap mass spectrometry. Methodology/Principal Findings Despite high inter-individual variability, concentration of β-thymosins increases with an inversely proportional trend to postmenstrual age (PMA: gestational age plus chronological age after birth) reaching a value more than twenty times higher than in adult whole saliva at 190 days (27 weeks) of PMA (thymosin β4 concentration: more than 2.0 µmol/L versus 0.1 µmol/L). On the other hand, the ratio between thymosin β4 and thymosin β10 exhibits a constant value of about 4 along all the range of PMA (190–550 days of PMA) examined. In order to investigate thymosin β4 origin and to better establish the trend of its production as a function of gestational age (GA), immunohistochemical analysis of major and minor salivary glands of different pre-term fetuses were carried out, starting from 84 days (12 weeks) of gestational age. Reactive granules were seen in all glands with a maximum of expression around 140–150 days of GA, even though with high inter- and intra-individual variability. In infants and adults reactive granules in acinar cells were not observed, but just a diffuse cytoplasmatic staining in ductal cells. Significance This study outlines for the first time that salivary glands during foetal life express and secrete peptides such as β-thymosins probably involved in the development of the oral cavity and its annexes. The secretion increases from about 12 weeks till to about 21 weeks of GA, subsequently it decreases, almost disappearing in the period of expected date of delivery, when the gland switches towards the secretion of adult specific salivary peptides. The switch observed may be an example of further secretion switches involving other exocrine and endocrine glands during foetal development.

Cardiac Adverse Effects of Early Dexamethasone Treatment in Preterm Infants: A Randomized Clinical Trial

This study evaluates the effects of early administration of dexamethasone on left ventricle dimensions and their clinical significance in preterm infants. Fifty preterm infants with birth weight ≤ 1250 g and gestational age ≤ 30 weeks were randomly assigned after 72 hours of life to the dexamethasone group (n = 25) or to the control group (n = 25). The treated infants received dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the 7th day). Serial echocardiographic measurements of end systolic interventricular septum thickness, end diastolic interventricular septum thickness, end systolic left ventricle posterior wall thickness, end diastolic left ventricle posterior wall thickness, left ventricle end diastolic diameter, and left ventricle end systolic diameter were taken before starting dexamethasone, on days 3 and 7 of treatment, 7 days after the interruption of treatment, and at the 28th day of life. Five infants of each group were excluded by the final analysis because of the lack of a complete cardiac evaluation, leaving 20 treated and 20 control infants. Infants receiving dexamethasone had a significantly larger increase in mean septal and left posterior wall thickness during the treatment and 7 days after the dexamethasone weaning. The mean left ventricle diameter of treated infants was significantly lower than that of control infants from the 7th day of treatment to the 28th day of life. Four neonates (20%) in the dexamethasone group developed left ventricular myocardial hypertrophy without left ventricle outflow tract obstruction, showing signs of decreased cardiac output and ischemic changes on ECG. The daily fluid intake was increased to 200 ml/kgto ensure an adequate preload volume, and the complete resolution of left ventricle hypertrophy was obtained within the 2nd to 3rd week after dexamethasone weaning. Preterm infants receiving an early (< 96 hours of life) short course of dexamethasone develop a left ventricular myocardial hypertrophy that can be symptomatic and clinically significant. Preterm infants included in future studies with the goal to find the minimum dose and duration of dexamethasone treatment should be strictly monitored echocardiographically for this side effect.

Transabdominal amnioinfusion treatment of severe oligohydramnios in preterm premature rupture of membranes at less than 26 gestational weeks.

Objective: To evaluate the efficacy of transabdominal amnioinfusion on feto-neonatal and maternal morbidity and feto-neonatal mortality. Methods: We studied 71 patients with preterm premature rupture of membranes (pPROM) at <26 weeks of gestational age. Thirty-four patients were managed expectantly and 37 underwent serial transabdominal amnioinfusion with saline every 7 days in case of persistent oligohydramnios. Results: Latency period pPROM delivery, week of delivery (26.0 vs. 22.4, p < 0.001), neonatal weight (922 vs. 602, p < 0.01) and the percentage of intrauterine fetal survival were higher in treated than in control groups (64.8 vs. 32.3%, p < 0.01). In amnioinfusion-treated patients, we did not note a higher rate of complications from infection during both pregnancy and puerperium. In the amnioinfusion group, fluid loss within 6 h after infusion is the main variable in predicting pulmonary hypoplasia and neonatal survival. Conclusions: Our data suggest that amnioinfusion seems to be a low fetal and maternal risk technique that modifies the natural history of pPROM, improving fetal intrauterine stay and survival.