Francesca Serrao

Cortical visual function in preterm infants in the first year.

OBJECTIVE To assess visual function in low-risk preterm infants at 3, 5, and 12 months corrected age to determine whether the maturation of visual function in the first year is similar to that reported in term-born infants. STUDY DESIGN Seventy-five low-risk infants (25.0-30.9 weeks gestation) underwent ophthalmological examinations and a battery of tests (fix and follow, visual fields, acuity, attention at distance, and fixation shift) designed to assess various aspects of visual function at 3, 5, and 12 months corrected age. RESULTS The results were comparable with normative data from term-born infants in all tests but fixation shift, suggesting that maturation of most aspects of visual function is not significantly affected by preterm birth. In contrast, >25% of preterm infants failed the fixation shift test at 3 months, with a higher percentage of failing at 5 and 12 months. CONCLUSIONS There is a specific profile of early visual behavior in low-risk preterm infants, with a high percentage of infants failing a test that specifically assesses visual attention and provides a measure of cortical processing.

Early assessment of visual function in preterm infants: how early is early?

BACKGROUND Several studies reported on various aspects of visual function at term age and in the first months after birth but less has been reported in preterm infants before they reach termequivalent age. AIMS To assess the suitability of a battery of tests of visual function for use in infants born at <33weeks gestation (GA) and assessed before 34weeks post-menstrual age (PMA); to evaluate the distribution of the findings according to GA, and to compare the data with those previously published on preterm infants assessed at 35weeks PMA. STUDY DESIGN Cross-sectional study. SUBJECTS Sixty-four preterm infants with a GA <33weeks were studied. OUTCOME MEASURES We used a battery of visual function tests previously validated at 35 and 40weeks PMA in low-risk preterm infants. All the infants in this current study underwent the same assessment before 34weeks PMA. RESULTS Before 31weeks PMA most infants could not be reliably assessed because of clinical instability, whilst after 31weeks PMA most infants could be assessed and they showed progressive maturation in their responses with PMA. Some items (spontaneous ocular motility, horizontal tracking, tracking a coloured stimulus, and ocular fixation) showed similar results at 32-33weeks PMA to those found in low-risk preterm at 35weeks PMA. Ocular movements to a target and arc tracking were the items with the most immature responses. CONCLUSIONS Our results provide further evidence that a structured assessment of visual function can be used in clinical routine and for research purposes in infants as young as 31weeks PMA.

Visual function assessment in late-preterm newborns

AIM To describe the development of visual functions in a population of low-risk late preterm infants. SUBJECTS AND METHODS Eighty low-risk late preterm with a gestational age between 34.0 and 36.9 weeks were assessed at birth and at term equivalent age (TEA) using a structured visual assessment battery. The results were compared to those previously obtained in term born infants using the same battery. RESULTS For 5 items (spontaneous ocular motility, ocular motility with target, fixation, horizontal tracking and color tracking) the results were similar both at birth and TEA; for the other 4 (vertical and arc tracking, ability to discriminate striped black/white targets and attention at distance) visual findings at TEA were more mature than at birth. Comparing the responses in late preterm at TEA and term-born infants at 48 h of life, only 2 items (attention at distance, ability to discriminate black/white stripes) were different, with more mature findings in late preterm infants. CONCLUSIONS Our results show that in late preterm some aspects of visual functions have a progressive maturation infants between birth and TEA, confirming that the time between birth and term age appears to be crucial for the development of these abilities.

Perceptual-motor abilities in pre-school preterm children

BACKGROUND Several studies report a high percentage of premature infants presenting perceptual motor difficulties at school age. The new version of the Movement Assessment Battery for Children allows the assessment of perceptual-motor abilities in children from the age of 3years. AIMS To evaluate early perceptual-motor abilities in prematurely born children below the age of 4years. STUDY DESIGN The Movement Assessment Battery for Children 2nd edition was administered to 105 low-risk prematurely born children (<32weeks gestation) and in a control group of 105 term-born children matched for age and sex. All children were assessed between the age of 3years and 3years-11months. RESULTS 63 children (60%) had total scores above the 15th percentile, 15 (14.3%) had scores between the 5th and the 15th percentile, and 13 (12.4%) below the 5th percentile. The remaining 14 children (13.3%) refused to perform or to complete the test. The difference between preterm and control group was significant for total scores, Manual Dexterity and Aiming and Catching scores. In the preterm group there was a correlation between age at testing, total scores and Aiming and Catching subscores. The Movement ABC-2 subscores were significantly lower in children born below 29weeks. CONCLUSION Perceptual-motor difficulties can already be detected on the assessment performed before the age of 4years. Prematurely born children assessed between 3years and 3years-3months appeared to have more difficulties in performing the test than the older ones or their age matched term-born peers. These findings support the possibility of a delayed maturation in the younger age group.

Longitudinal assessment of perceptual-motor abilities in pre-school preterm children.

OBJECTIVE To verify the value of early perceptual-motor assessment in preterms. METHODS The M-ABC2 was performed below the age 3 years-4 months and 1 year later. RESULTS At 4 years children showed a significant improvement in the scores and reduced rate of refusals. CONCLUSION Early findings may be related to delayed maturation.

Effect of Early Expressed Human Milk on Insulin-Like Growth Factor 1 and Short-Term Outcomes in Preterm Infants.

Aims Preterm breast milk contains high levels of bioactive components, including insulin-like growth factor 1 (IGF-1), that are reduced by Holder pasteurization. Animal studies have shown that milk-borne IGF-1 is likely absorbed intact in a bioactive form by the intestines. The aim of this study was to assess if early non-pasteurized expressed breast milk nutrition may affect IGF-1 plasma levels in premature infants. We also investigated the possible association between early expressed milk nutrition and short-term outcomes. Methods Fifty-two preterm infants with gestational age < 31 weeks were divided into two groups according to expressed breast milk intake (< or ≥ 50 mL/Kg/day) until 32 weeks of postmenstrual age when blood sampling for IGF-1 analysis was performed. Results In our population, early expressed breast milk does not affect IGF-1 plasma levels (p 0.48). An association was observed between early expressed milk nutrition and a lower incidence of bronchopulmonary dysplasia, sepsis, feeding intolerance, need for parenteral nutrition and length of hospitalization. Conclusions Contrary to the results in some animal studies, our results did not seem to show that early expressed breast milk can help to maintain postnatal IGF-1 near foetal levels in preterm infants. The observed protective effect of expressed breast milk on short-term outcomes can be the starting point for further study of the effects of non-pasteurized human milk in preterm infants.

When arrhythmia is in the air: Images of the Month

Following a 26-week gestation period, a 1200-g female infant was born by vaginal delivery after preterm rupture of the membranes. Antenatal corticosteroids were not administered prior to delivery. After oral-tracheal intubation and ventilation, the Apgar score was 4 at 1 min and 7 at 5 min. On admission to the neonatal intensive care unit, the clinical condition of the neonate appeared compromised and she was ventilated with the following settings: high frequency oscillatory ventilation, maximum mean airway pressure of 16 cmH2O, frequency of 15 Hz, maximum tidal volume of 2.5 mL/kg, inspired oxygen partial pressure of 1. An initial chest X-ray was diagnostic of severe respiratory distress syndrome than complicated by pulmonary hypertension. Three doses of surfactant were administered, and 20 ppm nitric oxide was started. At approximately 7 h of age, she developed severe hypotension that persisted in spite of inotropic support (dopamine, dobutamine, adrenaline, hydrocortisone). After 46 h of age, her condition worsened and she became hypoxic and acidotic; she suddenly exhibited signs of vascular collapse and became markedly cyanotic. Cardiac monitoring showed tachycardia with absence of R wave and a widened QRS complex as with severe myocardial compromise. A new chest-abdomen X-ray was performed (Fig. 1). What diagnoses should you consider? (Answer on page 925)

Semipermeable membranes and hypernatremic dehydration in preterms. A randomized-controlled trial

BACKGROUND Hypernatremic dehydration is a complication of preterm infants with reportedly high morbility. In preterm infants, this happens due to a combination of low fluid intake, transepidermal water loss (TEWL), and immaturity of kidney function. Semipermeable membranes are self-adhesive membranes that can be applied as an artificial skin to reduce TEWL. AIMS To test the hypothesis that early application of a semipermeable membrane (Tegaderm™) in preterm infants ≤30 weeks could result in a significant reduction of hypernatremia (serum Na > 145 mEq/l) during the first 15 days of life. STUDY DESIGN Randomized controlled trial (UMIN000010515). SUBJECTS 164 consecutive newborns with gestational age ≤ 30 weeks, absence of congenital skin defects, and duration of admission ≥ 15 days. Patients were randomized to receive semipermeable membrane (n = 82) or no membrane (n = 82) for the first 15 days of life. OUTCOME MEASURES The primary endpoint of the study was the incidence reduction of hypernatremia (Na > 145 mEq/l). Secondary endpoints included: postnatal weight loss (WL) and time to birth weight (BW) recovery. RESULTS Incidence of hypernatremia in the control and semipermeable membrane group was 59.7% and 41.6%, respectively (p = 0.030). Postnatal WL was larger in the control group (13.9 ± 5.6% vs 11.1 ± 3.4%, p = 0.005) and occurred later than the semipermeable membrane group (5.4 ± 2.3 vs 4.5 ± 1.4 days, p = 0.005). Time to BW recovery was also longer for control group (13.5 ± 4.3 vs 11.9 ± 3.2 days, p = 0.016). CONCLUSIONS Early application of skin semipermeable membrane to ≤30 week preterm is associated with decreased incidence of hypernatremia, decreased %WL, and earlier BW recovery. No complications were observed with membrane application.

Intrauterine infection caused by herpes simplex virus type-1 in the setting of recurrent maternal infection

Sir, Herpes simplex virus (HSV) type-1 causes about 10% of intrauterine herpes simplex diseases. Reviewing the literature only seven living infants with an intrauterine HSV type-1 infection have been reported (Glover and Atherton 1987; Jay et al. 1995; O’Riordan et al. 2006; Marquez et al. 2011). Of the survivors for whom outcome was reported, one infant had good clinical outcome (Glover and Atherton 1987) and two had developmental delay (Jay et al. 1995; Marquez et al. 2011). We would like to report an intrauterine HSV type-1 infection in a preterm infant, subsequent to a recurrent orolabial maternal infection, because of two interesting aspects: the first is that our patient is one of the few infants to have survived intrauterine HSV type-1 infection, and the second is that this case implicates the possible aetiological role of the HSV type-1 in the pathogenesis of multicystic dysplastic kidney (MCDK). The male infant was born at 30 weeks gestation weighing 2130 g with a prenatal diagnosis of ascites and multicystic right kidney. Renal dysplasia was diagnosed at 20 weeks and ascites at 24 weeks of gestation. At that time, maternal serology revealed only a prior infection with rubella, cytomegalovirus, HSV, mumps and chickenpox. Pregnancy history was unremarkable, except for orolabial HSV infections at 8 and 12 weeks of gestation. Family history was negative for renal abnormalities. At 29 weeks, a paracentesis was performed; bacterial and viral cultures on the ascitic fluid were negative, polymerase chain reaction (PCR) for viral agents was not done on the ascitic fluid. At birth, infant showed hepatosplenomegaly and bilateral hydrocele; no cutaneous abnormalities were present. The abdominal ultrasound documented ascites, enlarged liver with parenchymal inhomogeneity, splenomegaly and dysplastic right kidney with multiple non-communicating cysts, compatible with MCDK. About 100 mL of ascitic fluid was taken at the paracentesis, and PCR on ascitic fluid was positive only for HSV type-1. At 48 h of life PCR and cultures for HSV type-1 were performed in the bronchoalveolar and cerebrospinal fluid, in the conjunctival and pharyngeal smears and in the urine: only PCR in the pharyngeal smear was positive. Neonatal HSV IgM was negative, whereas HSV IgG levels were compatible with prior maternal infection. The cerebral ultrasound and the fundus oculi examination were normal. Diagnosis of intrauterine HSV type-1 infection was made and therapy with acyclovir was administered for 21 days. Serial ultrasounds showed a decrease in residual ascites until resolution after 12 days of antiviral therapy, whereas hepatosplenomegaly and hepatic parenchymal inhomogeneity resolved after one week. At the end of therapy, HSV type-1 PCR in the pharyngeal smear was negative. At 40 days of life, the infant was discharged. At three months of life, auditory brainstem response test was normal and magnetic resonance imaging excluded cerebral abnormalities, whereas renal computed angioscintigraphy with 99m-Tc-DTPA showed functional exclusion of the right kidney with compensatory hypertrophy of the contralateral one. At one year, renal follow-up was unchanged. We hypothesised that unilateral MCDK could be related to HSV type-1 infection, because the mother had orolabial HSV infections at 8 and 12 week of gestation, just during the embryological development of the kidney. Indeed, foetal kidneys develop between the 5th and the 15th week of gestation. Aetiology of MCDK includes genetic disturbance, teratogens, urinary tract obstructions and intrauterine viral infections. Viruses implicated in the aetiology of the MCDK are cytomegalovirus, enterovirus and adenovirus (Chan et al. 2007; Hains et al. 2009), but until now no aetiological involvement of HSV type-1 infections in the pathogenesis of MDCK has been reported. Unfortunately, we failed to demonstrate a conclusive correlation between HSV type-1 infection and MCDK, because we did not find the virus in the urine, but likewise this correlation cannot be excluded. Therefore, we think that future research on the HSV type-1 aetiology of renal abnormalities would be needed.

The management of pain: non-pharmacologic analgesia

“Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Each individual learns the application of the word through experiences related to injury in early life”[1]. It is now clear that premature and full-term newborns have the neuroanatomical pathways from the periphery to cortex required for nociception. In fact by the 23th week of gestation painful stimuli are associated with physiologic, hormonal, and metabolic markers of the stress response. Indeed pain perception may be greater because of immaturity of descending inhibitory pathways [2]. Preterm infants are particularly vulnerable to brief and long term effects of pain and stress because system modulating sensory experience is immature[3,4]. Neonatal intensive care involves a high number of diagnostic and therapeutic procedures which are associated with pain for preterm and sick newborn infants. In addition to immediate unpleasantness, painful experiences can imprint themselves indelibly on the nervous system amplifying and causing typically painless sensations to be experienced as pain. Pharmacological and non-pharmacological intervention (NFI) are recommended for painprevention and pain management [5]. In order to achieve optimum efficacy, both pharmacological and NFI additionally require a reduction of external stimuli, such as loud noise and bright light [6]. NFI is recommended for procedural and mild pain [7]. NFI for procedural pain is a treatment that is initiated before and during the procedure in order to reduce the physiological consequences of nociceptive transmission provoked by the procedure. Therefore NFI could be considered a “pre-emptive analgesia”. NFI activate the “gate control mechanism”, some intervention lead to an endogenous endorphin dispersal which contributes to modulation of the pain pulse at the level of spinal cord [8,9], some other may elicit activation of neuropeptides systems that can achieve an analgesic effect through the potentiation of opioid activity [10], There is sufficient evidence to support the use of NFI, particularlybreast feeding, sweet-tasting solutions, kangaroo care, non nutritive suckling, swaddling and facilitate touching for the common needle-puncture procedures [11-13]. Other NFI such as music, olfactory and multisensory stimulation areto some degree beneficial to neonates who undergo painful procedures [14,15]. Despite our limited understanding of the underlying mechanisms of actions of NFI, there seems to be few documented short-term harms from their use. NFI need a collaborative effort. Support from the administration and leadership, both formal and cultural, is crucial for the implementation of NFI[16].