Effects of oral iodine supplementation in very low birth weight preterm infants for the prevention of thyroid function alterations during the neonatal period: results of a randomised assessor-blinded pilot trial and neurodevelopmental outcomes at 24 months.

The trace element iodine (I) is essential for the synthesis of thyroid hormones. Parenteral nutrition solutions, formula milk, and human breast milk contain insufficient iodine to meet recommended intake for preterm infants. Iodine deficiency may affect thyroid function and may be associated with morbidity or neurological outcomes. The primary objective is to assess the evidence that dietary supplementation with iodine affects thyroid function during the neonatal period. The design was a randomised controlled pilot trial. Infants who met the inclusion criteria were enrolled through consecutive sampling and assigned to two different groups. The setting was a Spanish university hospital. Ninety-four patients with very low birth weight (under 1500 g) were included. Intervention group: 30 µg I/kg/day of iodine in oral drops given to 47 infants from their first day of life until hospital discharge. Control group: 47 infants without supplements. Formula and maternal milk samples for the determination of iodine content were collected at 1, 7, 15, 21, 30 days, and at discharge. Blood samples were collected for thyroid hormones. Neurological development was assessed at 2 years of age (Bayley III Test). Infants in the supplemented group reached the recommended levels from the first days of life. The researchers detected the effects of iodine balance on the plasma levels of thyroid hormones measured during the first 12 weeks of age. The trial assessed the impact of the intervention on neurodevelopmental morbidity.Conclusion: Thyroid function is related to iodine intake in preterm infants. Therefore, supplements should be added if iodine intake is found to be inadequate. The analyses found no effects of iodine supplementation on the composite scores for Bayley-III assessments in all major domains. The study results indicate potentially important effects on language development related to low iodine excretion during the first 4 weeks of life What is Known: • Thyroid function is related to iodine intake in preterm infants. • Preterm babies on formula preparations and with exclusive parenteral nutrition are at high risk of iodine deficiency. What is New: • Iodine intake should be monitored during the neonatal period. • Iodine supplements should be added if iodine intake is found to be inadequate.

Genetic predisposition to fetal and neonatal cancer.

BACKGROUND: Neonatal tumors represent an extremely rare and heterogeneous disease with an unknown etiology. Due to its early onset, it has been proposed that genetic factors could play a critical role; however, germline genetic analysis is not usually performed in neonatal cancer patients PATIENTS AND METHODS: To improve the identification of cancer genetic predisposition syndromes, we retrospectively review clinical characteristics in 45 patients with confirmed tumor diagnosis before 28 days of age, and we carried out germline genetic analysis in 20 patients using next-generation sequencing and directed sequencing. RESULTS: The genetic studies did not find any germline mutation except patients diagnosed with bilateral retinoblastoma who harbored RB1 germline mutations. CONCLUSIONS: Our results suggest that genetic factors have almost no higher impact in most neonatal tumors. However, since the heterogeneity of the tumors and the small sample size analyzed, we recommend complementary and centralized germline studies to discard the early onset as an additional criterion to take into account to improve the identification of cancer genetic predisposition syndromes in neonates.

Successful treatment of intrauterine cytomegalovirus infection with an intraventricular cyst in a dichorionic diamniotic twin gestation using cytomegalovirus immunoglobulin.

Congenital cytomegalovirus (CMV) infection is the leading cause of severe congenital abnormalities. CMV immunoglobulin (CMVIG) may lower risk for symptomatic disease in congenital CMV infection. In a twin pregnancy, only one fetus shows CMV infection, raising a dilemma about intervention since the uninfected fetus would be exposed to treatment unnecessarily. CMVIG (2 × 200 U/kg) was given due to high viral load and development of an intraventricular cyst. The cyst growth plateaued, no other brain damage developed, and at 8 months, the infant was symptom-free. CMVIG appears appropriate to treat intrauterine CMV infection in this setting.

VIM-Klebsiella oxytoca outbreak in a Neonatal Intensive Care Unit. This time it wasn't the drain.

OBJECTIVE: We describe an outbreak of VIM-carbapenemase Klebsiella oxytoca (VIM-Kox) in a NICU. MATERIALS AND METHODS: Prospective Epidemiological Surveillance:Systematically (weekly screening cultures) or on admission, if the patient had a history of previous colonization by VIM-Kox.Clinical cultures, done if infection was suspected.Other possible microorganism sources were investigated: their mothers (rectal microbiota), milk packages and preparation apparata in the lactodietary section, echocardiagram transductors, cribs, the sinks (faucets and drains), washing bowls, etc.Molecular typing was performed using the DiversiLab (bioMérieux) system on all VIM-Kox isolated from environment or patients (one by neonate). RESULTS: We identified 20 VIM-Kox cases, the most only presented colonization, but 4 showed infection. Three of the ten sinks (drains) in our NICU, were positive for VIM-Kox. Another four drains harbored P.aeruginosa, S. maltophilia and/or Enterobacter sp. Nevertheless the VIM-Kox bacteria in the sinks (drains) were not the same as those in the patients, who showed three different strains. CONCLUSIONS: A VIM-Kox colonization or infection outbreak in a NICU is described. Rather than environment, not even drains, the source of the outbreak was other patients. The outbreak was relatively brief, as a result of the rapidness with which appropriate measures were taken and followed.

Experimental study showed that adding fortifier and extra-hydrolysed proteins to preterm infant mothers' milk increased osmolality.

AIM: Measuring milk osmolality after adjustable fortification is clinically relevant, as values exceeding recommended safety thresholds might result in gastrointestinal consequences. The aim of this study was to evaluate the effect of four fortification levels and storage time on the osmolality of human milk. METHODS: This was an experimental study using 71 spare samples of fresh breastmilk collected from 31 mothers of preterm infants. Osmolality was measured before and after adding commercial human milk fortifier containing dextrinomaltose and hydrolysed proteins at four different concentrations. Measurements were performed at various points during the 23 hours after fortification. RESULTS: The mean basal osmolality of the 71 human milk samples was 296 ± 14 milliosmoles (mOsm)/kg, and these remained stable over a period of 23 hours. Just after fortification, the four fortified formulas showed higher osmolalities than the nonfortified human milk, ranging between 384 ± 14 and 486 ± 15 mOsm/kg, respectively (p < 0.01). This osmolality increased significantly from 20 minutes to 23 hours after fortification (p < 0.05). CONCLUSION: Adding fortifier and extra-hydrolysed proteins to human preterm milk increased osmolality, and these osmolality levels also increased with time. We recommend evaluating the risk of hyperosmolality when a higher fortification level is needed, to avoid gastrointestinal problems.

Dichorionic twin pregnancy discordant for anencephaly: two cases with different management.

BACKGROUND: Prevalence ofanencephaly in dichorionic twins is higher than in singleton pregnancies. The authors report two cases with two different management strategies. CASE 1: Spontaneous dichorionic diamniotic twin pregnancy with the second twin diagnosed with anencephaly at 12 weeks gestation. Selective feticide was performed at the age of 13.2 weeks. Vaginal delivery occurred at 39 weeks, and birth weight was 2,850 g. CASE 2: Dichorionic diamniotic twin pregnancy discordant for anencephaly in the second twin was diagnosed at 13 weeks gestation. An expectant management was decided. Preterm delivery occurred at 35 weeks due to hydramnios of the affected fetus, delivering a healthy newborn weighing 2,300 g and an anencephalic neonate who died immediately after delivery. CONCLUSION: Anencephaly should be diagnosed as soon as possible, idealistically at 11-13+6 weeks ultrasound (US) scan, in order to offer the most appropriate counselling to the parents, ranging from selective feticide or expectant management. This short series suggests that selective early feticide may increase gestational age and birth weight.

[Chylous fistula following lymphadenectomy in breast cancer]. / Fístula quilosa tras linfadenectomía axilar en cáncer de mama.

Axillary lymph node dissection remains an integral part of surgical treatment in patients with invasive breast cancer and axillary lymph node metastases. Chylous leakage after axillary lymph node dissection is infrequent. We report the case of a patient with an advanced local breast cancer that was subsidiary to surgery treatment after neoadjuvant chemotherapy. She had a postoperative chylous leakage; it was successfully treated conservatively in the postoperative course. Chylous leakage an infrequent complication alters axillary lymph node dissection, which has a conservative management in most published studies.

Identification of risk factors associated with nosocomial infection by rotavirus P4G2, in a neonatal unit of a tertiary-care hospital.

A rotavirus outbreak in newborns admitted to the 'La Paz' University Hospital, Madrid was detected, followed up and controlled. Uninfected children were selected as control subjects. Samples of faeces were taken once or twice weekly from all the newborns, including those who were asymptomatic and who were admitted to the neonatal unit for early detection of rotavirus and the positive were separated from the rest of the neonates. Contact-related precautions were taken for all patients, and alcohol solutions were used for hand washing. During the months of the outbreak, 1773 children were admitted to the hospital, 131 of whom were affected by the rotavirus infection (7.4%). Of these, 72 (55%) had symptomatic infections. In the first month of the outbreak, nine cases of necrotizing enterocolitis were diagnosed (one patient developed massive intestinal necrosis). The infections (symptomatic and asymptomatic) presented a bimodal distribution caused by a new outbreak of rotavirus type P4G2 after two patients who had acquired the infection outside the hospital were admitted when the first outbreak was subsiding. The characteristics of cases and controls were analysed using bivariate and multivariate methods (non-conditional multivariate logistic regression) to identify four risk factors strongly associated with rotavirus infection: premature birth, infections other than rotavirus, malformation, and changes in glycaemia and/or presence of jaundice.

[Anomalous systemic arterial supply to the lower lobe of the right lung: a rare finding]. / Vascularización anómala sistémica del lóbulo inferior del pulmón derecho: una patología infrecuente.

Vascularization of a segment or lobe of the lung from a systemic artery is a rare anomaly. The lower left lobe is usually involved and clinical presentation typically includes hemoptysis, chest pain, exercise-related dyspnea or murmurs. Some patients are asymptomatic and discovery is fortuitous. Diagnosis depends on images, with angiography and, most recently, helicoid CT scan proving most useful. Treatment is nearly always surgical, with or without prior embolization of the anomalous vessel.We report the case of a 31-year-old man with anomalous systemic arterial supply to the lower right lobe discovered while we examined a pulmonary node that appeared benign. The location was unusual. We discuss diagnostic procedures and assess the relation between this condition and lung sequestration and hypogenetic lung syndrome.

Reactogenicity of DTPa-HBV/Hib vaccine administered as a single injection vs DTPa-HBV and Hib vaccines administered simultaneously at separate sites, to infants at 2, 4 and 6 months of age.

An open, randomised, multicentre trial was performed to assess the reactogenicity and safety profile of the administration of a candidate Haemophilus influenzae type b (Hib) conjugate vaccine with a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine as a single injection (Group 1) versus the simultaneous administration of the latter vaccine (DTPa-HBV) and an available Hib conjugate vaccine (Group 2) in opposite thighs, as a primary vaccination course to healthy infants at 2, 4 and 6 months of age. Eight hundred and eighty five infants (9.3+/-1.4 weeks old) were randomly allocated to Group 1 (n=665) and Group 2 (n=221). Oral polio vaccine was given concomitantly to all subjects. Blood samples (pre-vaccination and 1 month after the third dose) were obtained from a subset of infants (Group 1, 73; Group 2, 22) for serological determinations. Local and general symptoms were recorded by parents on diary cards. 2614 diary cards (Group 1, 1966; Group 2, 648) were collected. There were no statistically significant differences in the incidence of local and general symptoms between groups. Pain such that the infant cried when limb was moved was reported in 0.6 and 0.2% in groups 1 and 2, respectively. Redness and swelling (>20 mm in diameter) were recorded between 2.1 and 3% in both groups. Fussiness preventing normal activities was the most frequently reported general symptom in both groups (1.6 and 1.9% in groups 1 and 2, respectively). Fever (rectal temperature >39.5 degrees C) was reported in 0.4% (Group 1) and 0.3% (Group 2). All subjects included in the immunogenicity analysis had seroprotective or seropositive titres to the diphtheria, tetanus, hepatitis B and pertussis components of the vaccines. About 99 and 100% of infants had anti-PRP titres > or =0.15 mcg/ml in groups 1 and 2, respectively. This study indicates that DTPa-HBV vaccine given in a single injection with a candidate Hib conjugate vaccine has a similar reactogenicity profile to that of two commercially available vaccines (DTPa-HBV, Hib) given in two simultaneous injections to infants 2, 4 and 6 months of age.

Treatment with plasmapheresis and intravenous immunoglobulin in pregnancies complicated with anti-PP1Pk or anti-K immunization: a report of two patients.

BACKGROUND AND OBJECTIVES: In addition to anti-D alloantibody, other antibodies such as anti-K antibody and anti-PP1Pk antibody have been reported to cause severe haemolytic disease of the newborn (HDN). HDN caused by anti-K results not only from destruction of red cells but also from suppression of erythropoiesis. Anti-PP1Pk has been associated with abortion early in pregnancy. We report on two patients, one with anti-PP1Pk and the other with anti-K, who were treated with plasmapheresis and intravenous immunoglobulin (IVIG) during pregnancy in an attempt to reduce the plasma antibody levels. MATERIALS AND METHODS: The patient with anti-PP1Pk had lost all seven previous fetuses in the first trimester and therefore therapy in this patient was started at 8 weeks of gestation. The second patient had been sensitized to the K antigen through blood transfusion and had had two intrauterine fetal deaths at 26 weeks of gestation with signs of hydrops fetalis. Treatment in this patient was started during the 16th week of pregnancy. RESULTS: As a result of therapy, the antibody titre was reduced in both patients. In the first patient a healthy infant was delivered by Caesarean section at 37 weeks of gestation. The second patient gave birth at 36 weeks of gestation. Neither newborn required exchange transfusion. CONCLUSION: In our two patients, plasmapheresis combined with IVIG proved successful in the management of fetomaternal incompatibilities where the mechanism of fetal loss differs from the classical anti-D.

[Facial asymmetry with crying: a neurophysiological study and clinical account of this entity]. / Asimetría facial con el llanto: estudio neurofisiológico y recuerdo clínico de esta entidad.

OBJECTIVE: The objectives of this study were to determine in our newborn population the frequency of facial asymmetry during crying or congenital hypoplasia of the depressor anguli oris muscle (DAOM) without associated major malformations and to evaluate the contribution of electrophysiological studies in the diagnosis of this anomaly. PATIENTS AND METHODS: We performed a prospective study of the living newborns with facial asymmetry which did not need to be admitted to the hospital and that were delivered without the use of forceps in our hospital during 4 consecutive years. Newborn evaluation included physical examination, facial nerve electroneurography and DAOM electromyography. RESULTS: This anomaly without major malformations was present in 0.348/1,000 newborns. Electrophysiological studies demonstrated a normal latency in the facial nerve electroneurography and an absence or reduced number of motor unit potential without signs of denervation in the electromyography. CONCLUSIONS: Diagnosis of this entity is important to exclude facial nerve palsy. Only a physical examination is necessary for a correct diagnosis.

Use of polymerase chain reaction and quantitative antibody tests in children born to human immunodeficiency virus-1-infected mothers.

The diagnosis of human immunodeficiency virus (HIV) infection in children born to HIV-infected mothers is complicated by the presence of passively acquired maternal antibodies, and exclusion of infection in these infants remains problematic. The use of genome detection by polymerase chain reaction (PCR) amplification and the quantification of anti-HIV-1 antibodies were examined as methods for early diagnosis. Blood samples were taken from 84 non-breast-fed infants of HIV-infected mothers in five Italian and Spanish centres, a subgroup of children enrolled in the European Collaborative Study (ECS) for whom clinical and immunological information has been documented from birth. Whole blood was added to glycigel cryopreservative, stored, and tested in the United Kingdom by a nested PCR method. Antibody to HIV-1 was detected and quantified by titration using a gelatin particle agglutination test. PCR sensitivity and specificity were assessed. Twenty-one of the 84 children tested were infected. The estimated PCR sensitivity ranged from 0% (95% CI 0-26%) on day 1, 57% (19-85) on day 7, to 63% (33-92) on day 30. The negative predictive value of PCR ranged from 85% (83-88) on day 0 to 98% (94-100) at 3 months of age. On average, the level of maternal antibody halved every 33 days (31-36.5) in uninfected children. Between 6 and 9 months of age, increases in antibody titres in infected children were not more informative than absolute levels. These findings suggest that antibody measurement may supplement genomic diagnosis and that this collection method provides an alternative to the use of dried blood spots.

Fetal anaemia due to pyruvate kinase deficiency.

Pyruvate kinase deficiency was diagnosed in an infant by umbilical vessel sampling at 30 weeks' gestation. Although three previous hydropic siblings had been stillborn or died in the neonatal period, this infant survived with transfusion dependent haemolytic anaemia. Prompt fetal diagnosis of pyruvate kinase deficiency is feasible and allows better management of hydrops fetalis due to this disorder.

Immunological follow-up in children born to HIV-1 infected mothers.

From November 1985 to January 1990 we examined 156 children born to 154 HIV-1 seropositive mothers every 3 months. Eighty-seven infants were over 18 months by January 1990. Six of them met the CDC criteria of HIV-1 infection or died from AIDS; a transmission rate of 7%. Six of the children aged less than 18 months also met the CDC criteria of HIV-1 infection. These 12 infected children were compared with the 81 presumably unifected children. The perinatal findings were similar in both groups. Most of the HIV-1 infected babies showed early abnormalities in humoral and cellular immunity, hypergammaglobulinemia, low percentage of CD4 circulating lymphocytes and increased spontaneous in vitro immunoglobulin production. These changes were persistent in the HIV-1 infected children, but sporadic in those uninfected. Immunological abnormalities were frequently found before clinical symptoms appeared. We conclude that repeated immunological abnormalities in babies born to HIV-1 seropositive mothers are suggestive of HIV-1 infection.

Intrapartum chemoprophylaxis of early-onset group B streptococcal disease.

A randomized study in 121 pregnant women carrier of group B streptococci is undertaken in order to assess the administration of 500 mg of intrapartum ampicillin intravenously to interrupt mother-to-fetus group B streptococcal transmission. In the prophylaxis group there was a significant reduction in neonatal colonization (3.7 vs. 42.9%) and in severe neonatal colonization (0 vs. 25%). There was no case of group B streptococcal sepsis in the prophylaxis group compared to 4.6% (3 cases) in the control group (P greater than 0.05). Clinically infected newborns represented 3.3% in the prophylaxis group vs. 13.8% in the control group. When the organism was isolated during delivery in the vagina or amniotic fluid, prophylaxis was quickly followed by second negative cultures. Ampicillin levels in the amniotic fluid were detected early, and they increased significantly till the third hour. Bactericidal levels in the umbilical cord were detected in 60% of newborns. All these findings support the usefulness of ampicillin prophylaxis in the prevention of early-onset group B streptococcal sepsis.

[Spanish Pediatric Association. Madrid. Human immunodeficiency virus infection. Spanish multicenter study]. / Asociación Española de Pediatría. Madrid. Infección por el virus de la immunodeficiencia humana. Encuesta multicéntrica española.

The results of an epidemiological survey in Spain organized by the "Spanish Pediatric Association" of children born to HIV+ mothers from 1981-1989 are presented. The objectives were, a) to document in the different parts of Spain the number of HIV+ children born to HIV+ mothers, and b) to identify the risk factors involved in the HIV infection. Only in public hospitals, a total of 1938 HIV+ children born to HIV+ mothers were identified. A systematic yearly increase of HIV+ newborns was evident since 1985. Madrid, Catalonia, Valencia, Basq and Andalucia communities incorporated 85% of all cases. 93% of mothers were IVDU and 51% of them were married. Prematurity occurred in 27% of cases and low birth weight in 33% of NB's. The rate of transmission in children over 18 months of age was 25.6% Breast feeding could be a risk factor in the transmission of HIV infection observed in children over 18 months of age. No other maternal risk factors responsible for the HIV transmission were identified. 12% of children died with AIDS. Clinical classification and evolution of HIV infection did not significantly differ from similar studies in other parts of the world. In spite of only public hospitals being involved, Spain has more identified HIV+ children than Italy, Switzerland, Federal Republic of Germany, United Kingdom, Sweden and Belgium combined. The pediatric centres with large number of cases require interdisciplinary pediatric specialized units to cope with the increase demand of medical services, now inadequate and insufficient. To fight drug use and HIV infection in Spain, health education and family support, are indispensable in trying to arrest the continuous spread the HIV infection.

Soluble class I histocompatibility antigens (s-HLA) and beta 2-microglobulin at delivery.

In this work we have quantified soluble class I histocompatibility antigens (s-HLA) and beta 2-microglobulin (beta 2 m) in sera of HIV+ or HIV- mothers at delivery and in cord blood sera of their newborn children. The results obtained for beta 2 m show that cord blood sera of newborn children have higher concentrations than their mothers, implying that most of the beta 2 m in the newborn is self-produced as described previously. s-HLA serum concentrations in the newborn children are significantly lower than in their mothers or in age-matched controls. Moreover, HIV+ mothers have significantly higher serum concentrations than HIV- mothers or an age-matched control group. These results suggest that s-HLA does not cross the placental barrier.

Polyasplenia, caudal deficiency, and agenesis of the corpus callosum.

Fullana et al. [Am J Med Genet (suppl. 2): 23-29, 1986] reported on 2 sibs with an autosomal recessive syndrome of caudal deficiency and polyasplenia anomalies. We report on a similar patient in which agenesis of the corpus callosum (ACC) was also found. Such an association has not been reported previously. This finding of ACC is to be interpreted as another midline anomaly rather than as a causally independent malformation.