Refinement of the critical 7p22.1 deletion region: Haploinsufficiency of ACTB is the cause of the 7p22.1 microdeletion-related developmental disorders.

Non-recurrent microdeletion (≤2 Mb in size) in 7p22.1 is a rarely described cytogenetic aberration, only recently reported in patients with developmental delay/intellectual disability, short stature and microcephaly. The size of the deletions ranged from 0.37 to 1.5 Mb, and reported genotype-phenotype correlations identified a minimum deleted region of 0.37 Mb involving the FBLX18, ACTB, FSCN1, RNF216 and ZNF815P genes. The authors suggested that deletion of ACTB, which encodes ß-actin, an essential component of the cytoskeleton, could be responsible for the clinical features observed in the patients with a 7p22.1 microdeletion. Here, we describe a 23-month-old child displaying developmental delay, short stature, microcephaly and distinctive facial features. Chromosomal microarray analysis performed using high-resolution SNP-array platform revealed a de novo interstitial 60 Kb microdeletion in the 7p22.1 region (from 5,509,127 bp to 5,569,096 bp, hg19) encompassing only two genes: FBXL18 and ACTB. To the best of our knowledge, this is the smallest deletion at 7p22.1 to date reported in medical literature (Pubmed). Combining our data with phenotypic and genotypic data of cases from literature, we were able to narrow the minimal critical region, which contained only two genes, i.e., FBXL18 and ACTB. Our finding is useful to perform a more accurate genotype-phenotype correlation and strongly strengthen the hypothesis that haploinsufficiency of ACTB is the main cause of the clinical phenotype observed in the patients with 7p22.1 microdeletions, facilitating genetic diagnosis and counseling.

How to administrate erythropoietin, intravenous or subcutaneous?

AIM: To determine whether adding recombinant erythropoietin to the intravenous (IV) solution and administering it as a 24-h continuous infusion would result in an erythropoietic effect not inferior to that seen with subcutaneous (SC) administration. METHODS: Infants weighing ≤1500 grams and ≤32 weeks of gestational age were randomly assigned at 72 h of life to receive erythropoietin (300 units/kg, 3 times a week until 36 complete weeks of postmenstrual age or discharge), either subcutaneously [erythropoietin subcutaneous (ESC) group] or added to IV fluids [erythropoietin intravenous (EIV) group]. RESULTS: One hundred infants were randomized (50 in the EIV group and 50 in the ESC group). The incidence of transfusions was comparable in the two groups, similar in baseline characteristics and haematologic values at study entry. Phlebotomy losses did not differ between groups, and at the end of the study, there were no differences in reticulocyte counts, transferrin saturation and ferritin. No differences in the incidence of side effects were observed. CONCLUSIONS: In preterm infants, continuous intravenous administration of erythropoietin was not inferior to SC dosing.

Infants born to mothers under phenobarbital treatment: correlation between serum levels and clinical features of neonates.

OBJECTIVE: Phenobarbital crosses the placenta quickly, and the balance between maternal and fetal blood is achieved in a few minutes. Data on the clinical outcomes of infants born to mothers under phenobarbital treatment during pregnancy show that they are at risk of adverse events, such as sedation and abstinence syndrome. The aim of this study was to analyse the correlation between serum levels of phenobarbital and clinical features of neonates. STUDY DESIGN: Twenty-three infants born between 2001 and 2008 were studied. Maternal, neonatal and pharmacological variables were considered. RESULTS: Eleven infants displayed symptoms related to phenobarbital. Withdrawal syndrome was seen in seven infants and sedation syndrome was seen in four infants. One infant had severe cardiorespiratory depression at birth. None of the infants had severe neonatal abstinence syndrome. No statistically significant differences were found between symptomatic and asymptomatic infants. At birth, the mean serum level of phenobarbital of the 23 infants was 15.4 [standard deviation (SD) 6.2] µg/ml. A peak (16.1 µg/ml, SD 5.5) was seen on Day 3, followed by a gradual decrease to non-therapeutic levels (<10 µg/ml) by Day 8 (9.3 µg/ml, SD 1.0). Phenobarbital levels were higher in symptomatic infants than asymptomatic infants, although the difference was not statistically significant. CONCLUSIONS: Serum levels of phenobarbital remained in the therapeutic range for both mothers and infants, and reduced gradually in infants. However, some infants displayed symptoms related to phenobarbital. As such, a clinical pharmacological surveillance protocol is necessary.

Ophthalmia neonatorum: what kind of prophylaxis?

OBJECTIVE: Conjunctivitis during neonatal period occurs in 1-12% of all babies. Ophthalmia neonatorum is an acute muco-purulent conjunctivitis occurring in the first month of birth. It is essentially an infection acquired during vaginal delivery. The most frequent infectious agents involved in ophthalmia neonatorum are Chlamydia trachomatis and Neisseria gonorrhoeae. METHODS: Topical ocular prophylaxis must be instituted early after birth. Recommended prophylactic regimen are: 1% nitrate solution; 1% tetracycline solution; 1% erythromycin solution; 2.5% povidone-iodine solution; and fusidic acid. RESULTS: Evidence suggests better outcomes using 1% tetracycline solutions even if there is the risk of selecting drug resistant bacteria. However, even the widespread used nitrate solution can cause a chemical conjunctivitis, arguing against its widespread use. CONCLUSIONS: Fusidic acid is a relatively new promising therapy even if there are still few data about its use. None of the used regimens has the optimal risk-benefit profile to suggest a widespread use.

Toward a bioethical issue: induced multiple pregnancies and neonatal outcomes.

Assisted reproductive technology has made great progress during the last three decades. After the initial enthusiasm, many ethical, legal and social issues related to the application of these procedures began to evolve. Multifetal pregnancy and fetal reduction, embryo cryopreservation, preimplantation genetic diagnosis, risks of birth defects and other adverse outcome associated with assisted reproductive technology are issues that have to be addressed building future collaborative studies and continuing the debate on related ethical issues.

Massive fetomaternal hemorrhage and late-onset neutropenia: description of two cases.

Massive fetomaternal hemorrhage (FMH) occurs in approximately 1:1,000 deliveries. In most cases, the cause is not identified. The clinical manifestations and the prognosis of a FMH depend on the volume of the hemorrhage and the rapidity with which it has occurred. We describe two cases of chronic massive fetomaternal hemorrhage with favorable outcome. During the follow-up, both infants showed late-onset neutropenia, which was not previously reported in healthy, growing infants with history of massive FMH.

Neonatal outcomes in triplet pregnancies: assisted reproduction versus spontaneous conception.

AIMS: The purpose of this study is to compare neonatal outcomes of spontaneously conceived triplets with triplets conceived by assisted reproduction. METHODS: This was a retrospective cohort study of all cases from assisted triplet pregnancies and controls from spontaneous triplet pregnancies. A total of 24 triplet pregnancies were studied: six spontaneous and 18 assisted. The following variables were evaluated in all newborns: prematurity, birth-weight, small for gestational age, birth-weight discordance, Apgar scores, major neonatal morbidity and perinatal mortality. RESULTS: Gestational age (33+/-1 vs. 33+/-2 weeks) and birth-weight (1760+/-256 vs. 1907+/-452 g) were similar in spontaneous and assisted triplet pregnancies. There were no significant differences in the rates of small for gestational age, discordance, and major neonatal morbidity. In the assisted reproduction group only the following cases were recorded: 1 surgically treated patent ductus arteriosus, 1 feto-fetal transfusion syndrome, 2 grade II intraventricular hemorrhage, 1 Cri du Chat syndrome and 1 stillbirth with malformations. CONCLUSIONS: This study is unable to assess the influence of assisted reproduction on the neonatal outcomes of triplet pregnancies. However, the results suggest that the incidence of major neonatal morbidity, especially malformations, might increase due to assisted reproduction. This finding requires further confirmation.