The effect of gestational age on developmental outcomes: a longitudinal study in the first 2 years of life.

BACKGROUND: Extremely low and very low gestational age (ELGA and VLGA) constitutes a risk factor for development even in absence of cerebral damage, as an immature central nervous system is exposed to invasive and inadequate stimulation. We tested the hypothesis that GA impacts developmental outcomes and trajectories of preterms without major cerebral damage in the first 2 years of life, expecting poorer developmental outcomes and higher rate of impairment with the decreasing of GA. We also evaluated whether GA, together with developmental outcomes in the first year of life, was related to developmental outcomes at 24 months. METHODS: Eighty-eight infants, divided into three GA groups (ELGA: ≤28 weeks; VLGA: 29-32 weeks; full term: >37 weeks) were assessed longitudinally at 6, 12, 18 and 24 months using the Griffiths Mental Development Scales. RESULTS: Use of a repeated measure multivariate analysis of variance resulted in several significant findings. GA was associated with the developmental quotient (DQ) scores (P= 0.006); and locomotor (P < 0.001), eye and hand co-ordination (P= 0.016) and performance (P= 0.040) sub-scale quotient (SQ) scores; age of evaluation was also associated with DQ scores (P= 0.002), and locomotor (P < 0.001) and performance (P < 0.001) SQ scores. In particular, ELGAs exhibited lower DQ and SQ scores compared with the VLGA and full-term groups; some ELGAs showed mild, moderate or severe cognitive impairments, while few VLGAs mild impairments. Linear regression analysis showed that GA (P= 0.034) and 12-month developmental outcome (P < 0.001) were related to 24-month developmental outcome. CONCLUSIONS: Different developmental trajectories emerged in relation to GA, with poorer developmental outcomes and higher rates of impairment in ELGAs and few mild impairments in VLGAs. The relevance of taking into account both GA and repeated assessments in the first 2 years of life was shown.

Hospitalization for lower respiratory tract disease in preterm infants: effects of prophylaxis with palivizumab.

To evaluate the effect of palivizumab prophylaxis on hospitalization for acute respiratory tract infections (RTI) in preterm infants, a prospective study was performed on a cohort of preterm infants [gestational age (GA) <32 weeks], admitted at birth to a Neonatology Intensive Care Unit (NICU) (follow-up: 30-month after discharge). 154 palivizumab-recipients and 71 palivizumab-non-recipients were evaluated. During follow-up, a similar rate of hospitalization for RTI was found in the two groups (11.3% in palivizumab-non-recipients and 15.58% in palivizumab-recipients, p=0.39). However, when only infants hospitalized during their first respiratory syncytial virus (RSV) epidemic season and with a chronological age <6 months at admission were considered, the incidence rates for hospitalization was six-fold lower in the palivizumab-recipients (p=0.007). This study contributes to the definition of epidemiological data on RTI among preterm infants in Italy. These data support the usefulness of palivizumab prophylaxis for prevention of hospitalization for RTI in young preterm infants during the expected RSV epidemic season.

Environmental factors associated with stress in mothers of preterm newborns.

AIM: In this study the effects of environmental and structural features of two different neonatal intensive care unit (NICU) settings on the time course of psychological distress in mothers of preterm infants were investigated. METHODS: Levels of psychological distress in 21 mothers of premature infants hospitalized in the NICU of the Salesi Hospital were compared with levels of psychological distress in 21 mothers of premature infants from the NICU of the Sant'Orsola Hospital at three different times during hospitalization. RESULTS: Data showed that mothers from the NICU of the Salesi Hospital, where there is no presence of any specialized figure and the access for parents to the unit is ruled by time schedules, reported higher levels of psychological distress than mothers from the NICU of the Sant'Orsola Hospital, characterized by the continuous presence and contact with the medical staff, which included physiotherapists and clinical psychologists, and free access to the unit for parents. Moreover, levels of psychological distress increased over time in mothers from the Salesi Hospital while levels of distress decreased or were simply maintained over time in mothers from the Sant'Orsola Hospital. CONCLUSIONS: The present findings suggest that providing mothers with the opportunity of discussing the infant's clinical state with health professionals and receiving psychological support on a regular basis may reduce stressful feelings.

Dopamine D4 receptor (DRD4) polymorphism and adaptability trait during infancy: a longitudinal study in 1- to 5-month-old neonates.

We have examined the relationship between the common dopamine D4 receptor (DRD4) exon III repeat polymorphism and infants' behavior measured with the Italian version of the Early and Revised Infancy Temperament Questionnaires (EITQ/RITQ) in 122 Italian neonates at 1 and 5 months of life, when the genetic contribution to the behavior can be more clearly assessed. Two-way (genotype x age) analysis of variance revealed a significant correlation with the temperamental subscale of adaptability [F(1, 120) = 5.26, P < 0.02]. At 1 month of life (early assessment), infants with long (L) DRD4 alleles presented significantly low scores (L 2.61 +/- 0.073; S 2.84 + 0.79; Newman-Keuls P = 0.03) in comparison with the high scores of infants with short (S) alleles (L 2.4 +/- 0.059; S 2.25 +/- 0.57). These differences were not detected at 5 months of life (late assessment), denoting a strong environmental effect at this age on the genetic background. These results confirm and extend the genetic influence of the DRD4 gene in human temperament at birth.

The preterm infant's antibody response to a combined diphtheria, tetanus, acellular pertussis and hepatitis B vaccine.

Several combined vaccines have recently been developed, in order to improve the implementation of immunization programmes and increase the coverage for each vaccine. As the response of preterm infants may vary depending on the vaccination schedule and the vaccine product, it should be evaluated specifically as new vaccines become available. In this study we have examined the antibody response to a combined diphtheria, tetanus, acellular pertussis, and hepatitis B vaccine (DTPa-HBV), given as a primary vaccination course at 3, 5 and 11 months of postnatal age, in 34 preterm infants (mean gestational age (GA) = 32.0 weeks) in comparison with 28 term infants. At the end of the primary course, preterm infants had antibody concentrations for pertussis 69 kDa antigen and diphtheria toxoid that were significantly lower than those of term infants; preterm infants with GA < or = 31 weeks had antibody concentrations for pertussis 69 kDa antigen and HBsAg that were significantly lower than those of preterm infants with higher GA; anti-HBs antibody levels correlated with GA. However, the combined DTPa-HBV vaccine elicited seroconversion to all its components in all but two infants, one term and one preterm, after the second dose and a total seroconversion after the third dose. We conclude that preterm infants may be immunized with a combined DTPa-HBV vaccine, starting at the same chronological age, as term infants.

Prevention of allergies of infants: breast-feeding and special formulas. Influence on the response to immunization.

Infant formulas containing partially hydrolyzed cow milk-proteins are used for the prevention of allergy when maternal milk is not available, and, in preterm infants, also for improving gastric emptying. The nutritional adequacy of such formulas has not yet been completely defined. As the type of feeding may influence the antibody response to immunization, the aim of the present study was to evaluate the antibody response to oral polio virus immunization in term infants and to acellular pertussis and hepatitis B immunization in preterm infants, exclusively fed a partially hydrolyzed cow-milk formula during the first 5 months of life, in comparison with exclusively breast-fed infants. Active immune response occurred in all the infants after the second dose of immunization and no significant difference in the antibody titres was found according to the type of milk. On the basis of these results, it seems that protein nutrition based exclusively on a partially hydrolyzed formula does not impair the response to immunization in both preterm and term infants.

Clinical development of a combined diphtheria, tetanus, acellular pertussis, and hepatitis B vaccine in Italy.

In Italy, oral polio vaccine and diphtheria and tetanus (DT) and hepatitis B (HB) vaccinations are required by law. At present, infants receive DT and HB by two separate intramuscular injections during one visit, and most receive an additional injection of acellular pertussis vaccine at the same time. Although simultaneous administration of the vaccines has the advantage of only one medical visit, it is time-consuming for staff, very expensive, painful to the infants, and stressful for parents. A much better solution would be to administer a ready-to-use mixture containing all the vaccines, provided that this combination vaccine had good local and systemic safety profiles and clinical and immunologic efficacy. To evaluate such a combination vaccine in healthy infants at 3, 5, and 11 and at 2, 4, and 6 months of age, a multicenter clinical study is underway in Italy.

Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants.

The influence of dietary long chain polyunsaturated fatty acid (LCP) supply, and especially of docosahexaenoic acid (DHA), on evoked potential maturation, was studied in 58 healthy preterm infants using flash visual evoked potentials (VEPs), flash electroretinography (ERG), and brainstem acoustic evoked potentials (BAEPs) at 52 weeks of postconceptional age. At the same time, the fatty acid composition of red blood cell membranes was examined. The infants were fed on breast milk (n = 12), a preterm formula supplemented with LCP (PF-LCP) (n = 21), or a traditional preterm formula (PF) (n = 25). In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar; in the PF group the morphology was quite different and the wave latencies were significantly longer. This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower. Moreover, a higher level of erythrocyte LCP, especially DHA, was found in breast milk and PF-LCP groups compared with the PF group. ERG and BAEP recordings were the same in all three groups. These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available.

Iron nutrition and iron status changes in Italian infants in the last decade.

Two groups of 9-15 month old Italian infants were studied, at a 9 years' interval, to evaluate and compare feeding practices and their effect on iron status. Nutritional iron supply has increased in the last decade, due to a larger use of breast milk and iron-fortified infant formulas. In 1983, 21.6% of infants were breast-fed for 5 months or more, compared with 50.6% in 1992. In 1983, 73.3% of infants were fed on fresh cow's milk by the age of 6 months, compared with 7.6% in 1992. Consequently, iron status is markedly improved. In 1983, 5% of the examined infants were anemic and 20.7% showed iron deficiency without anemia, compared with 1.3% and 10.3% respectively in 1992. Our study supports the following recommendations: after 5 months of age exclusively breast-fed infants should receive an additional 1 mg/kg/die iron supplement and iron fortified formulas should be used instead of fresh cow's milk during the first year of life.

The effect of ammonium ion on the induction of (2'-5')-(A)n synthetase and (2'-5')-(A)n-dependent endoribonuclease activities by interferon in mouse BALB/C 3T3 cells.

Addition of ammonium chloride to interferon (IFN)-treated mouse L cells has been reported to reduce the antiviral state. Because (2'-5')-(A)n synthetase and (2'-5')-(A)n-dependent endoribonuclease (RNase L) activities have been implicated in the establishment of the antiviral state, we wish to ascertain if ammonium ions will also impair the IFN-elicited induction of these two enzymatic activities. To test this possibility, cell-free extracts were prepared from mouse BALB/C 3T3 cells and assayed for (2'-5')-(A)n synthetase and RNase L activities. Results of these studies show that when cells were incubated with IFN (100 or 500 U/ml) and ammonium chloride (20-40 mM) for 20 h, the induction of (2'-5')-(A)n synthetase by IFN is significantly suppressed. Based on binding to the specific radioactive (2'-5')-(A)n analog, (2'-5')p3A4,3'-[32P]pCp, on cross-linking to the periodate-oxidized (2'-5')p3A4,3'-[32P]pC, or on the (2'-5')-(A)n-enhanced degradation of [3H]-polyadenylated RNA, IFN (10-250 U/ml) was shown to cause a two- to sevenfold increase in RNase L activity. The induction of RNase L by IFN was blocked by simultaneous addition of ammonium chloride. However, 20 mM or 40 mM ammonium chloride did not affect the antiviral state in BALB/C 3T3 cells (based on a plaque reduction assay with 10-500 U/ml IFN). These results suggest that the establishment of the antiviral state is not necessarily coordinated with changes in the synthetase and the RNase L activities.

Plasma zinc concentrations in iron supplemented low birthweight infants.

We investigated the effect of prolonged iron supplementation of low birthweight infants on plasma zinc concentrations. Thirty infants (neonatal weight 820-2000 g) were examined at 6 or 12 months of life to assess their iron state and plasma zinc concentration. All of them were feeding on iron fortified formulas, which supply about 1 mg/kg/day of iron. In addition, 14 of them had been receiving 2 mg/kg/day of medicinal ferrous salts for at least five months. The other 16 were not given medicinal iron supplementation. Whereas iron state significantly differed in the two groups, plasma zinc concentrations were similar. Moreover, no zinc values below 75 micrograms/100 ml were found in any case. The results suggest that long term iron supplementation of low birthweight infants, at the recommended doses, does not influence zinc plasma concentrations unfavourably.

Intrauterine growth retardation: clinical problems in the management of the small-for-date baby.

The major neonatal problems of the small-for-date neonate (hypoglycemia, birth asphyxia, hypothermia, pulmonary disease, hematological problems and congenital malformations) are briefly reviewed. A series of 135 small-for-gestational-age neonates is briefly presented. There were 113 survivors (83.7%).

Double-stranded RNA-stimulated enzyme activities isolated from human placental extracts.

A (2'-5')An synthetase activity was isolated from human placental extracts by affinity chromatography on poly(rI) . poly(rC)-agarose. The oligonucleotide (2'-5')An was identified by (1) chromatography on PEI-cellulose and DEAE-cellulose, (2) inhibition of polypeptide synthesis in lysed rabbit reticulocytes (3) competition of the binding of pppA(pA)3,3'-[32P]pCp to rabbit reticulocyte lysates, and (4) alkaline phosphatase digestion. The synthetase activity in most placental preparations is activated by natural or synthetic dsRNA. However, in a few placental synthetase preparations, dsRNA is only marginally stimulatory and only becomes effective by prior treatment of the enzyme preparations with the calcium-dependent micrococcal nuclease. This suggests that there is an endogenous placental dsRNA contaminant in the enzyme preparations. In some synthetase preparations, a second dsRNA-stimulated product, tentatively identified as the nucleotide 5'-IMP, is also observed. Because the specific AMP deaminase inhibitor coformycin (10 microM) blocks the formation of IMP from ATP and causes a quantitative accumulation of AMP, and because the formation of IMp becomes independent of dsRNA when ADP or AMP is used in place of ATP, the presence of a dsRNA-stimulated ATP phosphohydrolase (ATPase) activity in human placenta is suggested.

Lack of correlation between free erythrocyte porphyrin and serum ferritin values at birth and at 2 months of life in low birthweight infants.

Red cell free erythrocyte porphyrin and serum ferritin determinations were performed on capillary blood specimens from 63 healthy infants weighing 2500 g or less at birth, during the first week of life, and, from 44 of them, again at 8-10 weeks. Free erythrocyte porphyrin values were high both at 3-7 days (mean 156 microgram/100 ml RBC) and at 8-10 weeks (mean 128 microgram/100 ml RBC). The respective serum ferritin values were also high (mean 226 and 107 ng/ml), excluding a depletion in iron stores. In addition, no correlation was found between free erythrocyte porphyrin and serum ferritin values either at birth or at age 2 months. These findings are consistent with an earlier hypothesis that in the presence of iron stores, the rate of iron release from the stores in low birthweight infants may not be sufficient to maintain optimal erythropoiesis if the demand is accelerated.