Infant formula, past and future: opportunities for improvement

Infant formulas provide nutritional support to health infants that promotes growth and development equivalent to that in healthy infants fed human milk. Formula-fed infants are not as well protected against infections, and there remain infants whose health, growth, and development may not be supported optimally by either the formulas currently available or human milk. Some infants may be better supported by genetically engineered formulas that contain immunity-enhancing antibodies or antigens. Formulas that contain cytokines promoting epithelial cell growth and integrity may be protective against necrotizing enterocolitis. Formulas containing proteins with genetically excluded allergenic epitopes or formulas with tolerogenic peptides may be useful in treating allergic diseases of suppressing the development of autoimmune disorders later in life. Formulas with genetically engineered biologically active substances might increase the absorption of nutrients in infants with compromised absorption or digestion, enhance host immunity and mucosal integrity, and, potentially militate or protect against the risk of disease.     

Neurodevelopment, growth, and viral load in HIV-infected infants

The relation of HIV-1 infection to infant growth and neurodevelopment was studied prospectively in a cohort of 65 infants born to women at risk for HIV infection. No differences were observed at birth between infected infants (INF) and uninfected infants (SR) of HIV-infected women, and infants of uninfected women (SN) with similar socioeconomic background and exposure to drugs. However, postnatal linear growth and cognitive-motor development of INF infants were impaired when compared to SR and SN infants. Declines in linear growth were observed within the first 6 months of life, whereas delays in neurodevelopment were first appreciated at 12 months. In INF infants, decreased linear growth was positively correlated with developmental delay. Moreover, growth and development were both correlated with HIV viral load. INF infants with high plasma HIV RNA copies (> 5 x 10(5)/ ml) at 6 months of life were more likely to exhibit severe growth and developmental delay than infants with a lower viral burden. The implications of these findings with respect to the mechanism of action of HIV-related growth and neurodevelopmental impairments are discussed.     

Frequency of neurologic disorders in the neonatal intensive care unit

Neonatal intensive care unit survival rates have improved significantly over the past decade. This improvement primarily reflects declining mortality rates among preterm infants. Neurologic morbidity increases with prematurity and is the major predictor of long-term disability. Accordingly, concern has been expressed that the burden of neurologic dysfunction among contemporary neonatal intensive care unit survivors may be increasing. To define the trends of neurologic disorders in the contemporary neonatal intensive care unit, all 4164 admissions between 1986 and 1995 to a tertiary neonatal intensive care unit were examined. Neonatal intensive care unit admissions (413 +/- 49 per year), proportion of births at less than 37 weeks (70 +/- 3% per year), and referral patterns were stable between 1986 and 1995. Over the study period, 773 (18%) of 4164 neonatal intensive care unit infants had a total of 1062 neurologic disorders. The neonatal intensive care unit mortality rate declined from 12% in 1986 to 4.2% in 1995 (P < .01). Neurologic disorders declined, from 27% of infants born in 1986 to 12% in 1995 (P < .001): 356 had seizures (14% in 1986 to 4% in 1995; P < .001), 235 had hypoxic-ischemic encephalopathy (8% in 1986 to 4% in 1995, P < .01), and 167 had intraventricular hemorrhage (7% in 1986 to 1.4% in 1995, P < .005). Frequency of congenital or chromosomal aberration affecting the nervous system was relatively constant (4.5% per year). Despite a three-fold improvement in neonatal intensive care unit survival between 1986 and 1995, the frequency of perinatally acquired neurologic disorders declined by more than 50%.     

Early maternal rejection affects the development of monoaminergic systems and adult abusive parenting in rhesus macaques (Macaca mulatta).

This study investigated the effects of early exposure to variable parenting style and infant abuse on cerebrospinal fluid (CSF) concentrations of monoamine metabolites and examined the role of monoaminergic function in the intergenerational transmission of infant abuse in rhesus monkeys (Macaca mulatta). Forty-three infants reared by their biological mothers and 15 infants that were cross-fostered at birth and reared by unrelated mothers were followed longitudinally through their first 3 years of life or longer. Approximately half of the infants were reared by abusive mothers and half by nonabusive controls. Abused infants did not differ from controls in CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), or 3-methoxy-4-hydroxyphenylgycol (MHPG). Abused infants, however, were exposed to higher rates of maternal rejection, and highly rejected infants had lower CSF 5-HIAA and HVA than low-rejection infants. The abused females who became abusive mothers in adulthood had lower CSF 5-HIAA than the abused females who did not. A similar trend was also observed among the cross-fostered females, suggesting that low serotonergic function resulting from early exposure to high rates of maternal rejection plays a role in the intergenerational transmission of infant abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Silent" patent ductus arteriosus and bronchopulmonary dysplasia in low birth weight infants

We conducted a clinical study on the antecedents of bronchopulmonary dysplasia (BPD) in 290 premature RDS infants with < or = 1.75 kg birth weight (BW). They were enrolled in a prospective trial of indomethacin treatment for "silent" patent ductus arteriosus (PDA), screened by 2-D echocardiographic and pulsed Doppler evaluation on the third day of life. The trial took place at the NICU of the Pediatric Department of Padua University between January 1987 and December 1991. Out of 290 infants screened, 96 had evidence of "silent" PDA (33%) and 77 responded to indomethacin treatment (80%). Comprehensively 79 (27%) developed BPD, and from these the incidence of BPD was statistically increased in infants with "silent" PDA, 47 out of 96 (49 +/- 9%), with respect to 32 out of 194 (16 +/- 3%) preterm infants without PDA. Statistical analysis showed that in preterm infants with "silent" PDA the development of BPD was correlated at 99% C.L. to their low BWs (mean BW = 1.13 kg): in fact the mean and the mode of BW distributions were statistically lower in the presence of BPD, 1.03 kg versus 1.24 kg, and 0.88 kg versus 1.65 kg respectively. Moreover, the preterm infants with "silent" PDA unresponsive to the first course of indomethacin and/or submitted later to surgical closure, presented a statistically lower BW with respect to the early responders, 1.06 kg versus 1.18 kg, and at the same time a statistically higher incidence of BPD (63 +/- 20% versus 43 +/- 9%). From these data we conclude that, although "silent", PDA increase per se the incidence of BPD, even if benefits from an early induced closure. Furthermore, a lower BW of infants affected by "silent" PDA represents a contributing factor to the development of BPD.     

A caregiver report comparison of temperamental characteristics of Down Syndrome and normal infants.

The temperamental characteristics of Down's syndrome (DS) and nonhandicapped infants were compared using the Infant Behavior Questionnaire (IBQ). 15 parents participating in a longitudinal study of their DS infants responded to a caregiver-report instrument, including the IBQ, at 3-mo intervals during the 1st yr of life. These data were compared to responses of a larger sample of parents of normal infants at 6, 9, and 12 mo of age. Differences at 2 or more ages were found for scales assessing smiling and laughter, duration of orienting, fear (distress and latency in approaching intense or novel stimuli), vocal activity, startle, and motor development. DS Ss had lower scores on smiling and laughter and higher scores on duration of orienting. DS Ss also had lower scores on scales measuring motor development and vocal activity and higher scores on fear and startle. No differences were found in activity level, distress to limitations, or soothability. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A dose-response study of the effect of flutamide on benign prostatic hyperplasia: results of a multicenter study

OBJECTIVE: To compare morbidity and mortality rates of low birth weight (LBW) and appropriate birth weight infants born at term, focusing on diarrheal and respiratory infections. STUDY DESIGN: A cohort of 133 LBW infants (1500 to 2499 gm) and 260 appropriate birth weight infants (3000 to 3499 gm), individually matched by sex and season of birth, were followed for the first 6 months of life. None had congenital anomalies and all were from poor families living in the interior of Pernambuco, northeast Brazil. Data on infant deaths, hospitalizations, and morbidity were collected prospectively through daily home visits (except Sundays) from birth through week 8, then twice weekly for weeks 9 to 26. The effects of birth weight were assessed with a variety of multivariable techniques, controlling for confounders. RESULTS: Of the LBW infants, 56% were wasted (thin), 23% were stunted, and 17% were both wasted and stunted. The LBW infants (median 2380 gm) experienced a sevenfold higher mortality rate and fourfold higher rate of hospitalization than appropriate birth weight infants. Almost all deaths and hospitalizations were in the postneonatal period. The LBW infants also experienced 33% more days with diarrhea and 32% more days with vomiting (p = 0.003 in each case). The prevalences of cough and fever were not significantly different. CONCLUSIONS: Infant deaths, hospitalizations, and diarrheal morbidity are increased in term LBW infants who have only a modest weight deficit.     

Defining the role of the bladder-neck sling in the surgical treatment of urinary incontinence in children with neurogenic incontinence

Mother squirrel monkeys stop carrying infants at earlier ages in high-demand (HD) conditions where food is difficult to find relative to low-demand (LD) conditions. To characterize these transitions in psychosocial development, from 10- to 21-weeks postpartum we collected measures of behavior, adrenocortical activity, and social transactions coded for initiator (mother or infant), goal (make-contact or break-contact), and outcome (success or failure). Make-contact attempts were most often initiated by HD infants, but mothers often opposed these attempts and less than 50% were successful. Break-contact attempts were most often initiated by LD infants, but mothers often opposed these attempts and fewer LD than HD infant break-contact attempts were successful. Plasma levels of cortisol were significantly higher in HD than LD mothers, but differences in adrenocortical activity were less consistent in their infants. HD and LD infants also spent similar amounts of time nursing on their mothers and feeding on solid foods. By rescheduling some transitions in development (carry-->self-transport), and not others (nursing-->self-feeding), mothers may have partially protected infants from the immediate impact of an otherwise stressful foraging task.     

Meningiomas in the region of the cavernous sinus: a review of 21 patients

OBJECTIVE: To compare the morbidities in the very low birthweight (VLBW; < 1500 g) and normal birthweight (NBW; > or = 2500 g) Malaysian infants during the first year of life. METHODOLOGY: Prospective observational cohort study of consecutive surviving VLBW infants and randomly sampled NBW infants born in the Kuala Lumpur Maternity Hospital between 1 December 1989 and 31 December 1992. Infants were followed up regularly during the first year of life, after correction for prematurity. RESULTS: Compared with NBW infants (n = 106), VLBW infants (n = 127) had significantly higher risk of failure to thrive (odds ratio [OR] = 8.0, 95% confidence intervals [CI]: 1.1 to 354.3), wheezing (OR = 3.7, 95% CI: 1.6 to 9.3), rehospitalization (OR = 2.3, 95% CI: 1.1 to 5.0), cerebral palsy (OR = 8.6, 95% CI: 2.0 to 77.6), neurosensory hearing loss (OR = 12.0, 95% CI: 1.7 to 513.6) and visual loss (7.9 vs 0%, P = 0.002). The mean mental developmental index (MDI) and mean psychomotor developmental index (PDI) at 1 year of age were significantly lower among VLBW infants (MDI 99 [SD = 28], PDI 89 [SD = 25]) than NBW infants (MDI 106 [SD = 18], PDI 101 [SD = 18]) (95% CI for difference between means being MDI: -14.1 to -1.7; and PDI: -17.6 to -6.0). Logistic regression analysis showed that among VLBW infants: (i) male sex, Malay ethnicity and bronchopulmonary dysplasia were significant risk factors associated with wheezing; (ii) longer duration of oxygen therapy during the neonatal period, seizures after the post-neonatal period and wheezing were significant risk factors associated with rehospitalization; and (iii) longer duration of oxygen therapy during the neonatal period was a significant risk factor associated with adverse neurodevelopmental outcome during the first year of life. CONCLUSIONS: Compared with NBW infants, VLBW Malaysian infants had significantly higher risks of physical and neuro-developmental morbidities.     

Movement analysis in infancy may be useful for early diagnosis of autism

All of the 17 autistic children studied in the present paper showed disturbances of movement that with our methods could be detected clearly at the age of 4-6 months, and sometimes even at birth. We used the Eshkol-Wachman Movement Analysis System in combination with still-frame videodisc analysis to study videos obtained from parents of children who had been diagnosed as autistic by conventional methods, usually around 3 years old. The videos showed their behaviors when they were infants, long before they had been diagnosed as autistic. The movement disorders varied from child to child. Disturbances were revealed in the shape of the mouth and in some or all of the milestones of development, including, lying, righting, sitting, crawling, and walking. Our findings support the view that movement disturbances play an intrinsic part in the phenomenon of autism, that they are present at birth, and that they can be used to diagnose the presence of autism in the first few months of life. They indicate the need for the development of methods of therapy to be applied from the first few months of life in autism.     

Emerging sensitivity to the timing and structure of protoconversation in early infancy.

Thirty-six 2-, 4-, and 6-month-old infants were videotaped while interacting with a female adult stranger engaging in either organized or disorganized 1-min peekaboo games. Two-month-old infants gazed and smiled equally at the stranger, regardless of the relative organization of the peekaboo game. In contrast, 4- and 6-month-old infants smiled significantly more and gazed significantly less in the organized peekaboo condition than in the disorganized peekaboo condition. These results suggest that from a diffuse sensitivity to the presence of a social partner, infants by 4 months develop a new sensitivity to the narrative envelope of protoconversation, in particular the timing and the structure of social exchanges scaffolded by adults. These observations are interpreted as evidence of developing social expectations in the first 6 months of life. This early development is viewed as announcing and preparing the communicative competence that blossoms by the end of the 1st year. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association of fungal colonization and invasive disease in very low birth weight infants

BACKGROUND: Fungi are common pathogens of nosocomial infections in the very low birth weight (VLBW) infants. The purpose of this study was to investigate the fungal colonization rate in VLBW infants and the association between fungal colonization and systemic fungal diseases. MATERIALS: Between January 1, 1996, and December 31, 1996, 116 infants with birth weight < 1500 g admitted to the neonatal intensive care unit of Chang Gung Children's Hospital in the first day of life were included in this prospective study. METHODS: Cultures from oropharynx, rectum, skin (groin and axilla), bag urine and endotracheal aspirates were obtained in the first 24 h after birth and weekly thereafter throughout their neonatal intensive care unit stay. Medical records were reviewed weekly. RESULTS: Fungal colonization was detected in 25 infants, among whom 17 infants developed colonization by 2 weeks of life. Candida albicans (61%) and Candida parapsilosis (29%) were the 2 most common organisms. The rectum (76%) was the most frequent site of colonization. Factors significantly associated with colonization were prolonged administration of antibiotic therapy, parenteral nutrition and intralipid emulsion. Three of 116 infants developed fungemia. The association between colonization and subsequent fungemia was demonstrated in 1 infant, representing 4% of colonized infants. CONCLUSION: Fungal colonization was detected in one-fifth of VLBW infants and represents a risk factor for fungemia. Because disease occurred in the absence of apparent colonization, factors other than colonization may contribute to invasive candidiasis.     

Social network relationships as sources of maternal support and well-being.

Explored the social networks available to mothers of infants, focusing on the contribution of specific relationships to maternal well-being. 43 mothers (aged 21–39 yrs) of 13-mo-old infants were asked to position individuals who were close to them in a network diagram and to indicate which of those individuals provided support. The mother's relationship with her husband and with the infant's maternal grandparents, mother's well-being in terms of affect and life satisfaction, and infant temperamental difficulty and infant–mother attachment security were assessed. Results reveal that mothers reported an average of 13 persons in their networks, but support was provided primarily by the husband, followed by the infant's maternal grandmother (particularly when there was more than 1 child), and 1 or 2 other family members and friends. Maternal affect and life satisfaction were related to infant difficulty and to support from and satisfaction with the spouse. Negative maternal affect was related to anxious/resistant attachment. Results affirm the importance of spousal support for mothers of infants in intact families. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Specific airway conductance in relation to postconceptional age during infancy

Thoracic gas volume (TGV) and airway conductance (Gaw) were measured in 69 healthy infants during the 1st yr of life, using an adaptation of the whole body plethysmographic technique in which a heated rebreathing system was used to eliminate temperature differences in respired gas. There was highly significant correlations between TGV and body wt (r=0.99), and between Gaw and TGV (r=0.97) in all the infants. However, the relationship between Gaw and TGV (i.e., specific conductance (SGaw)) was dependent on postconceptional age (PCA) in preterm infants, falling from 0.50 s-1-cmH2O-1 at 31 wk to 0.32 s-1-cmH2O-1 at 40 wk PCA. Gestational age and postnatal age per se did not affect this relationship, showing it to be a maturational event unaffected by the time of birth. After 40 wk, the decrease in SGaw was far more gradual throughout the 1st yr of life. Black and Chinese infants were found to have significantly higher values for SGaw than their White counterparts, which may be due to anatomical differences in nasal structure.     

Developmental changes in perception of nonnative vowel contrasts.

Discrimination of 2 German vowel contrasts was examined in English-learning infants of 6–8 and 10–12 mo of age using a head turn procedure. The younger infants were better able than the older infants to discriminate the nonnative contrasts, but performance at 6–8 mo was below levels that have been reported for nonnative consonant contrasts. A 2nd experiment using a habituation looking procedure showed that 4-mo-old infants discriminated both German vowel contrasts, but the 6-mo-olds could not. The findings are consistent with previous consonant work, revealing a shift from a language-general toward a language-specific pattern during the 1st yr of life. However, that shift begins earlier in development for vowels than for consonants. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of glutathione synthesis and gamma-glutamyltranspeptidase activities in tissues from newborn infants

Following the observation that the level of glutathione in leukocytes from human newborn infants was lower in preterm and in male infants, a study was designed to document the level of activities of glutathione synthesis and gamma-glutamyltranspeptidase during the development of preterm and term newborn infants. Measurements were performed in leukocytes from tracheal aspirates of oxygen dependent infants, and in leukocytes from cord blood. Contrary to the common belief concerning the development of antioxidant activity, the biosynthesis of glutathione was active in leukocytes from preterm infants; and by two days of life the activity of gamma-glutamyltranspeptidase reached 3 times the level of that seen in cord blood. Our results suggest that the maturity of these enzymes was not the limiting step in maintaining cellular glutathione levels. This represents new information concerning the maturation of a central antioxidant in tissue derived from preterm and term human newborn infants at risk of oxidant stress. This implies that sources of cysteine crossing freely the cellular membrane could be used by tissues of term and preterm infants to produce glutathione.     

Imitation and repetition of prosodic contour in vocal interaction at 3 months.

This study investigates vocal imitation of prosodic contour in ongoing spontaneous interaction with 10- to 13-week-old infants. Audio recordings from naturalistic interactions between 20 mothers and infants were analyzed using a vocalization coding system that extracted the pitch and duration of individual vocalizations. Using these data, the authors categorized a sample of 1,359 vocalizations on the basis of 7 predetermined contours. Pairs of identical successive vocalizations were considered to be imitations if they involved both partners or repetitions if they were produced by the same partner. Results show that not only do mothers and infants imitate and repeat prosodic contour types in the course of vocal interaction but they do so selectively. Indeed, different contours are imitated and repeated by each partner. These findings suggest that imitation and repetition of prosodic contours have specific functions for communication and vocal development in the 3rd month of life. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thyroid function in premature infants. The hypothyroxinemia of prematurity

Advances of perinatal and neonatal medicine have been associated with a progressive reduction in mortality of premature infants and a progressive increase in number of the surviving very low birth weight (VLBW) cohort less than 28 to 32 weeks gestation age. Hypothalamic-pituitary-thyroid (HPT) function is immature in most premature infants, and this is particularly true of the VLBW group. Accumulated information has allowed development of a unique nosology of HPT system disorders in these infants to facilitate thyroid function testing, test interpretation, and patient management.     

Relationship between concentration of serum leptin and fetal growth

The serum leptin concentration reflects the amount of adipose tissue in the body. Although fat deposition in the fetus in the third trimester markedly increases, the role of leptin during pregnancy has not been clarified. In the present study, whether or not the serum leptin concentration correlates with growth in utero was investigated, in addition to how leptin levels change in the first few days after birth. One hundred sixteen Japanese infants were divided into term (n = 91) and preterm groups (n = 25). Term infants were divided into 3 subgroups: birth weight appropriate for gestational age (AGA) (n = 44), birth weight large for gestational age (LGA) (n = 28), and birth weight small for gestational age (SGA) (n = 19). Longitudinal changes in the concentration of serum leptin after birth were examined in 48 infants. The serum leptin concentration was determined by RIA. No significant difference in leptin levels between cord sera and infants' sera obtained within the first 6 h of life (n = 28) was observed. Within the first 6 h of life, the concentration of serum leptin in LGA infants (12.8 +/- 10.2 ng/mL) and SGA infants (1.6 +/- 1.1 ng/mL) was significantly higher and lower, respectively, than that in the AGA infants (4.4 +/- 3.0 ng/mL) (P < 0.01). A significant positive correlation was found between the leptin concentration within 6 h of life and birth body weight (r = 0.59, P < 0.01). After birth, the concentration of leptin in LGA and AGA infants significantly decreased to the level in SGA infants within 72 h [corrected] of delivery (P < 0.05). After 72 h [corrected] of life, no significant differences in the concentration of leptin were observed among the three groups, and low levels continued to 7 days of age. These findings indicate that serum level of leptin correlates with fetal body weight gain.     

Neurodevelopmental outcomes of Ugandan infants with HIV infection: An application of growth curve analysis.

Neurodevelopmental outcomes of human immunodeficiency virus Type 1 (HIV-1)-infected infants of non-drug-using mothers were assessed in a controlled, prospective study from birth to 24 months with 3 groups: 61 infants of HIV-infected mothers, 234 uninfected infants of HIV-infected mothers (seroreverters), and 115 uninfected infants of uninfected mothers. Compared with seroreverters; and uninfected infants, HIV-infected infants demonstrated lower mental and motor development on the Bayley Scales and greater deceleration in their rate of motor development. HIV-infected infants with abnormal neurologic exams had lower motor and mental test scores and lower rates of motor Bayley Scales scores than their HIV-infected counterparts with normal neurologic exams. Contrary to prediction, no group differences in mean performance or growth rates were found on visual information processing on the Fagan Test of Infant Intelligence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)