Autism spectrum traits and visual processing in young adults with very low birth weight: the Helsinki Study of Very Low Birth Weight adults.

Visual processing problems may be one underlying factor for cognitive impairments related to autism spectrum disorders (ASDs). We examined associations between ASD-traits (Autism-Spectrum Quotient) and visual processing performance (Rey-Osterrieth Complex Figure Test; Block Design task of the Wechsler Adult Intelligence Scale-III) in young adults (mean age=25.0, s.d.=2.1 years) born preterm at very low birth weight (VLBW; <1500 g) (n=101) or at term (n=104). A higher level of ASD-traits was associated with slower global visual processing speed among the preterm VLBW, but not among the term-born group (P<0.04 for interaction). Our findings suggest that the associations between ASD-traits and visual processing may be restricted to individuals born preterm, and related specifically to global, not local visual processing. Our findings point to cumulative social and neurocognitive problems in those born preterm at VLBW.

Feeding the low-birth-weight infant. IV. Fat absorption as a function of diet and duodenal bile acids.

Fat absorption and fasting duodenal bile acids were studied at 11 to 68 days of age in 66 healthy preterm infants, gestational age of 31 to 36 weeks and birth weight of 1,230 to 2,160 g. The infants fed human milk received pooled, expressed milk (55%), partly supplemented (35%) with their own mother's expressed milk. Approximately 10% of the milk was given by breastfeeding once per day. All expressed human milk not fed immediately was pasteurized at 62 degrees C for 30 minutes. The other three groups of infants received an adapted formula (F1), F1 supplemented with taurine (F2), or F1 supplemented with taurine and cholesterol (F3). In each group, fat was provided at 6.75 g/kg/d. The formulas had a fat concentration of 4.5 g/100 mL, containing 57.6% of unsaturated fatty acids from vegetable oils. In the infants fed human milk, fat absorption was consistently high, and no correlation was found between fat absorption and postnatal age. In the formula-fed infants, fat absorption increased with postnatal age (r = .310 P less than .05). When the duodenal concentration of total bile acids was above the median (3.6 mmol/L), fat absorption in the formula-fed infants exceeded 80%. There was a linear correlation between fat absorption and duodenal bile acids (r = .630, P less than .001) in the formula-fed infants. In the infants fed human milk, such correlation was not observed, and their intraluminal concentration of bile acids always exceeded 3.6 mmol/L.

Serum immunoglobulins in preterm infants: comparison of human milk and formula feeding.

Serum concentrations of immunoglobulins (IgA, IgG, and IgM) were studied in 64 preterm infants with gestational age of 31 to 36 weeks (mean 33.2 weeks), between 1 week and 4 months after birth. Infants were fed solely human milk or formula based on cow's milk. Infants fed formula exhibited significantly higher IgA levels at the age of 9 to 13 weeks than infants fed human milk. Infants given human milk who received more than 60% of their feeding in the hospital from their own mother had significantly higher IgA levels at the age of 3 weeks than did those receiving less than 30% of their feeding from their own mother. At 1 week of age, formula-fed infants with gestational age of 31 to 33 weeks had a significantly lower mean IgG concentration than those with gestational age of 34 to 36 weeks. However, the two term subgroups of infants receiving human milk, had similar mean concentrations of IgG and the value for infants of 31 to 33 weeks of gestation was significantly higher than that for formula-fed infants at the same gestational age. Serum IgM concentrations were similar whether infants were receiving human milk or formula. The formula feeding caused a more rapid maturation of IgA than did human milk. Results suggest that preterm infants may absorb IgA from the milk of their own mothers and that preterm infants with gestational age of 31 to 33 weeks may absorb IgG from human milk.

Feeding the low-birth-weight infant. III. Diet influences bile acid metabolism.

Fasting duodenal bile acid concentrations and conjugation patterns were studied during the first 5 weeks of life in 65 low-birth-weight infants, 31 to 36 weeks of gestational age. One group was fed human milk. Approximately 55% of this milk was pooled, expressed, and pasteurized (62 degrees C for 30 minutes), 35% was similarly treated milk from the infant's own mother, and the remainder (10%) was provided by breast-feeding. The other infants, from 3 days of age, were fed one of three formulas: an adapted formula (F1), F1 supplemented with taurine (F2), or F1 supplemented with taurine and cholesterol (F3). The fasting intraluminal concentration of conjugated bile acids was higher in the infants fed human milk than in the infants fed formulas (F = 30.03, p less than .001) reflecting the higher concentrations of all individual bile acids. No significant increase over time was found in the concentration of total bile acids in any feeding group. Chenodeoxycholic acid concentrations, however, increased significantly over time in the infants fed human milk (r = .286, P less than .05). Thus, in the infants fed human milk, the ratio of cholates to chenodeoxycholates changed from 2.03 to 1.29 (P less than .001), whereas it remained stable (2.61) in the groups fed formula. Tauroconjugated bile acids predominated until at least 5 weeks of life in all the infants fed human milk, F2, or F3. In the infants fed F1, the concentration of glycoconjugates increased and that of tauroconjugates remained stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Feeding the low-birth-weight infant: I. Taurine and cholesterol supplementation of formula does not affect growth and metabolism.

Taurine and cholesterol are constituents of human milk that are present in smaller amounts in infant formulas. Infants fed such formulas have lower plasma and urine concentrations of taurine and of serum total cholesterol. In the present investigation, in infants of 31 to 36 weeks gestational age, the effects of supplementing a 1.5 g/100 mL whey-predominant formula with taurine alone or with taurine plus cholesterol were examined. Infants fed the supplemented formula were compared with infants fed the unsupplemented formula and with infants fed pooled, expressed human milk (185 mL/kg/d). Approximately 45% of the human milk provided to each infant was that of the infant's mother (35% pasteurized and 10% fresh). From the time of reaching a weight of 2,400 g to 4 months of age the last group of infants was fed ad libitum. No consistent statistically significant differences in growth, as measured by rate of gain in crown-rump length, crown-heel length, or head circumference, were observed. There was a tendency, however, for the formula-fed infants to gain weight more slowly before reaching 2,400 g and to gain weight more quickly after a weight of 2,400 g was attained to 4 months of age. No differences in concentrations of BUN, total serum proteins, or acid-base status were observed among the formula-fed groups. The concentration of BUN increased in the formula-fed groups compared with the group fed human milk during the last half of the study. The formula-fed infants tended to have higher total serum proteins and to be slightly more acidotic than the infants fed human milk prior to discharge at a weight of 2,400 g but not thereafter. Thus, infants fed 185 mL/kg/d gained weight at rates comparable to those for fetuses of the same gestational age. Supplementation of formulas with taurine or taurine plus cholesterol did not produce changes in growth or general metabolism discernible under the present experimental conditions.

Feeding the low-birth-weight infant: II. Effects of taurine and cholesterol supplementation on amino acids and cholesterol.

Plasma and urine concentrations of taurine were consistently lower in preterm infants fed unsupplemented formula than those observed in the infants fed human milk or formulas supplemented with taurine alone or with taurine plus cholesterol. Such supplementation of formula restored plasma and urine concentrations of taurine to those observed in the infants fed human milk. Taurine was the only amino acid that was present at lower concentrations in the infants fed unsupplemented formula than in those fed human milk. The other acidic and neutral amino acids were present in higher concentrations in the formula-fed infants than in the group fed human milk either during the early weeks of the study (serine, glutamine, glycine, alanine, tyrosine, and methionine) or consistently higher during the entire study (threonine, glutamate, citrulline, valine, isoleucine, leucine, and phenylalanine). Supplementation of formula with taurine plus cholesterol did not appear to have any effect on the amino acid concentrations in the plasma and urine, other than that on taurine itself. Plasma total cholesterol concentration decreased during the fifth to the 12th postnatal weeks of life in all feeding groups. It then returned to the concentrations found during the first and third postnatal weeks in all feeding groups except in the infants fed formulas supplemented with taurine plus cholesterol which had a greater decrease.

Milk protein quantity and quality in the term infant. I. Metabolic responses and effects on growth.

The growth and metabolic response of healthy, term infants during the first 12 weeks of life to feeding one of two formulas or human milk have been measured. Two groups of infants were fed ad libitum a 1.5 gm/100 ml bovine protein formula made up of either 60% whey and 40% casein proteins or 18% whey and 82% casein proteins. A third group of infants was breast-fed ad libitum. No consistent significant differences were observed among the groups with respect to rate of gain in weight, crown-rump length, crown-heel length, or head circumference. Blood urea concentration was significantly higher, and there was evidence suggesting compensation for an increased acid load from the second to the fourth weeks in both of the formula-fed groups compared with the breast-fed group. Blood cholesterol was significantly lower in both the formula-fed groups compared with the breast-fed group (P less than .001) and lower in the group fed the casein-predominant formula than it was in those fed the whey-predominant formula (P less than .05).

Milk protein quantity and quality in the term infant. II. Effects on acidic and neutral amino acids.

The response of the plasma and urine concentrations of acidic and neutral amino acids to two bovine protein formulas (1.5 gm/100 ml) containing, respectively, 60% whey proteins and 40% caseins or 18% whey proteins an 82% caseins was measured in term infants. These two groups of infants were compared with a group of infants that were breast-fed; all infants were fed ad libitum. Concentrations of citrulline, threonine, phenylalanine, and tyrosine in the plasma and urine were higher in the formula-fed infants than in the breast-fed infants and were a reflection of the amount of protein provided. Concentrations of tyrosine and phenylalanine were higher in the plasma and urine of infants fed the casein-predominant formulas than they were in those fed whey-predominant formulas. The opposite was true for threonine, which was present in higher concentrations in plasma and urine of infants fed whey-predominant formulas than it was in infants fed casein-predominant formulas. Concentrations of taurine were lower in the plasma and urine of formula-fed infants than they were in breast-fed infants. These differences give further evidence that formulas now in common use may provide a protein intake in excess of protein requirements and that there is a dietary requirement for taurine in man which is not satisfied by such formulas. Although these differences have not been established as nutritionally deleterious, neither can they be assumed to be entirely acceptable.

Neonatal herpes simplex virus infection: a report of 43 patients.

We present a series of 43 infants with neonatal herpes simplex virus infection treated at the Children's Hospital, University of Helsinki, during a 16-year period from 1970 to 1985. Twelve mothers (28%) had a history of genital herpes during pregnancy, and two had had labial herpes infection. Eight infants (19%) were delivered by cesarean section. In 14 (33%) infants symptoms appeared within 24 hours and in 26 (61%) they appeared within 7 days. The presenting symptoms were neurologic in 79%, cutaneous in 30%, respiratory in 19%, cyanosis/pallor/grayish skin in 16%, irritability in 12% and fever in 7%. Herpes simplex virus was detected most early and frequently in pharyngeal swabs, in one-third on Postnatal Days 2 to 5. Cerebrospinal fluid contained an increased amount of protein and/or pleocytosis in 72%. Abnormal electroencephalographic background activity appeared in 56% and electrical paroxysms in 41%. Six infants (14%) died, 9 (21%) were damaged severely and 6 (14%) were moderately or mildly damaged. Poor prognosis was associated with acute maternal illness at delivery, prematurity, visceral involvement and/or electrical paroxysms in the electroencephalograms. This study underlines the occurrence of intrauterine transmission of herpes virus, infections with neurologic manifestations, early symptomatology and the need for prompt diagnosis, brain biopsy in selected patients and antiviral therapy in neonates with herpes virus infection.

A population-based prospective survey of newborn infants with suspected systemic infection: occurrence of sporadic enterovirus and adenovirus infections.

BACKGROUND: Enterovirus outbreaks are known to occur in neonatal wards and enteroviruses may cause community-acquired sepsis-like disease in the neonatal period. Less well is known their possible role in suspected systemic infections during the perinatal period. OBJECTIVES: To investigate the occurrence of enterovirus infections in neonatal patients suspected of systemic infection. STUDY DESIGN: A population-based prospective survey was organized in the hospitals of the Greater Helsinki Region during 13 months in 1993-94. Criteria for enrollment included onset of symptoms before the age of 29 days and a decision, on clinical grounds, to take a blood culture for bacteria. Acute phase samples of blood, feces, nasopharyngeal swab, and cerebrospinal fluid, if available, were inoculated in monolayer cultures of four different cell lines. In addition, enterovirus infections were searched for using an enterovirus group-reacting IgM test. RESULTS: One hundred and thirty-seven patients had a sufficient number of specimens examined, and were thus evaluable. Most of the infants had the onset of the symptoms within a few days after birth. An enterovirus was isolated from four newborn infants (3%), while seven children (5%) were found to excrete adenovirus. Enteroviral antigen was detected in cell cultures inoculated with specimens from two additional infants. Virus-positive infants had no evidence of bacterial infection and did not show specific clinical signs or symptoms differentiating them from the rest of the study group. All enrolled infants recovered without sequelae. CONCLUSION: We conclude that sporadic viral infections may be common in neonatal patients with suspected systemic infection, and this should be taken into account when judging the etiology.

Thrombocytopenia in term infants: a population-based study.

OBJECTIVE: To assess the prevalence and causes of thrombocytopenia among full-term infants. METHODS: We conducted a 1-year, population-based surveillance study involving all full-term infants (at least 37 weeks' gestation) born to native Finnish women in Helsinki. In cases of thrombocytopenia (cord platelet count less than 150 x 10(9)/L) clinical risk factors were evaluated and immunologic studies were performed on both parents and on the infant; 95% confidence intervals (CIs) were calculated on the basis of binomial distribution. RESULTS: Platelet counts were done in cord blood from 4,489 infants, 84.9% of the study population. Eighty-nine infants had platelet counts below 150 x 10(9)/L (2.0%; 95% CI 1.5, 2.3) in cord blood and 11 were less than 50 x 10(9)/L (0.24%; 95% CI 0.10, 0.38). All causes of clinically important thrombocytopenia, those presenting with bleeding and requiring treatment, were related to fetomaternal alloimmune thrombocytopenia. The incidence of severe alloimmune thrombocytopenia was one in 1500 live births and one in 900 of all thrombocytopenia. An immunologic mechanism was involved in ten of 65 (15.4%; 95% CI 6.6, 24.2) infants studied and in four of 15 (26.7%; 95% CI 4.3, 49.1) cases of severe thrombocytopenia. CONCLUSION: Immunologic studies should be considered in all cases of severe neonatal thrombocytopenia for careful monitoring and prevention of potentially severe complications in subsequent pregnancies.

Diffusing capacity of the lung in school-aged children born very preterm, with and without bronchopulmonary dysplasia.

The aim of this study was to determine the extent to which bronchopulmonary dysplasia (BPD) affects the diffusing properties of lung tissue in childhood. Pulmonary function in 31 prematurely born children (BW. < 1250 g) was examined at ages 7-11 years. Twenty out of 31 prematurely born children met the criteria for BPD. The remaining 11 children had milder forms of neonatal lung disease. Twenty healthy children of the same age and born at term served as a control group. The diffusing capacity of the lung for carbon monoxide (DLCO) was measured by the single breath method. Lung volumes were determined in a body plethysmograph and expiratory flow rates with a flow/volume spirometer. DLCO values of children with histories of BPD did not differ significantly from those of the prematurely born children without BPD. However, DLCO values in both prematurely born study groups were significantly lower than those in controls born at term. Thoracic gas volumes measured with a body plethysmograph were similar in all groups. Spirometry demonstrated reduced flow rates in both BPD and non-BPD prematurely born children. The results suggest that some structural changes in lung tissues and airways persist for years in children who are born very preterm regardless of whether they develop BPD or not.

A national two year follow up study of extremely low birthweight infants born in 1996-1997.

OBJECTIVE: To study neurodevelopmental outcome in a two year cohort of extremely low birthweight (ELBW) infants at 18 months corrected age, to compare the development of the ELBW infant subcohort with that of control children, and to find risk factors associated with unfavourable outcome. STUDY DESIGN: All 211 surviving ELBW infants (birth weight < 1000 g) born in Finland in 1996-1997 were included in a national survey. The ELBW infants (n = 78) who were born and followed in Helsinki University Hospital belonged to a regional subcohort and were compared with a control group of 75 full term infants. A national follow up programme included neurological, speech, vision, and hearing assessments at 18 months of corrected age. Bayley infant scale assessment was performed on the subcohort and their controls at 24 months of age. Risk factors for unfavourable outcome were estimated using logistic and linear regression models. RESULTS: The prevalence of cerebral palsy was 11%, of all motor impairments 24%, of ophthalmic abnormalities 23%, and of speech delay 42%. No impairment was found in 42% of children, and 18% were classified as severely impaired. The prevalence of ophthalmic abnormalities decreased with increasing birth weight and gestational age, but the prevalence of other impairments did not. In the subcohort, a positive correlation was found between the date of birth and Bayley scores. CONCLUSION: Ophthalmic abnormalities decreased with increasing birth weight and gestational age, but no other outcome differences were found between birthweight groups or in surviving ELBW infants born at 22-26 weeks gestation. The prognosis in the regional subcohort seemed to improve during the short study period, but this needs to be confirmed.

Sound spectrographic analysis of pain cry in preterm infants.

Sound spectrographic cry analysis was performed on 302 cries of 48 preterm infants born at 30-37 gestational weeks. The cries were recorded during the first week of life and thereafter weekly until the infants were discharged. The control series comprised 54 cries from 27 fullterm healthy infants. The results showed that the cries of the smallest prematures compared with the controls were shorter, more high-pitched, and included bi-phonation and glide more often. The cry characteristics changed with increasing conceptual age and the older the child the more the cry pattern resembled that of the fullterm. The cries of the preterm infants when they had reached 38 conceptual weeks were similar to those of newly born fullterm infants. The results indicate that the gestational age should be taken into consideration in cry analysis.

Breast-feeding and the development of cows' milk protein allergy.

Early feeding with cows' milk (CM) may cause cows' milk allergy (CMA). Breast milk contains many immune factors which compensate for the undeveloped defence mechanisms of the gut of the newborn infant. We studied the effect of supplementary CM feeding at the maternity hospital on the subsequent incidence of CMA, the effects of formula and breast feeding on the subsequent immunologic types of CMA, and the importance of immune factors present in colostrum in the immune responses of infants with CMA. In a cohort of 6209 infants, 824 were exclusively breast-fed and 87% required supplementary milk while in the maternity hospital: 1789 received CM formula, 1859 pasteurized human milk, and 1737 whey hydrolysate formula. The cumulative incidence of CMA, verified by a CM elimination-challenge test, was 2.4% in the CM, 1.7% in the pasteurized human milk and 1.5% in the whey hydrolysate group. Among these infants, exposure to CM at hospital and a positive atopic heredity increased the risk of CMA. Of the exclusively breast-fed infants, 2.1% had CMA. Risk factors for the development of IgE-mediated CMA were: exposure to CM at hospital, breast-feeding during the first 8 weeks at home either exclusively or combined with infrequent exposure to small amounts of CM and long breast-feeding. The content of transforming growth factor-beta1 (TGF-beta1) in colostrum from mothers of infants with IgE-mediated CMA was lower than from mothers of infants with non-IgE-mediated CMA. In infants with CMA, TGF-beta1 in colostrum negatively correlated with the result of skin prick test and the stimulation of peripheral blood mononuclear cells to CM, but positively with infants' IgA and IgG antibodies to CM proteins. Feeding of CM formula at maternity hospital increases the risk of CMA, but exclusive breast-feeding does not eliminate the risk. Prolonged breast-feeding exclusively or combined with infrequent exposure to small amounts of CM during the first 8 weeks induces the development of IgE-mediated CMA. Colostral TGF-beta1 may inhibit IgE- and cell mediated reactions and promote IgG-IgA antibody production to CM in infants prone to developing CMA.

Maternal antihypertensive therapy with beta-blockers associated with poor outcome in very-low birthweight infants.

The progress of 36 very-low birthweight (less than or equal to 1500 g) infants born to mothers with pregnancy-induced hypertonia or pre-eclampsia was studied. During the first year of life, 7 out of 19 infants died when the mothers' antihypertensive regimen included beta-blockers. Four of the deaths occurred within 15 days. There were no deaths in 16 infants whose mothers were treated with other antihypertensive treatment (P = 0.006). These results suggest that maternal beta-blocker therapy may have adverse effects on the very-low birthweight infants.

Neurocognitive abilities in young adults with very low birth weight.

OBJECTIVE: Although severely preterm birth has been associated with impaired neurocognitive abilities in children, follow-up studies in adulthood are scarce. We set out to study whether adults born with very low birth weight (VLBW) (<1,500 g), either small for gestational age (SGA) (birth weight ≤-2 SD) or appropriate for gestational age (AGA), differ in a range of neurocognitive abilities and academic performance from adults born at term and not SGA. METHODS: As part of the Helsinki Study of Very Low Birth Weight Adults, 103 VLBW (37 SGA) and 105 term-born control adults (mean age 25.0, range 21.4-29.7 years) without major neurosensory impairments participated in the follow-up study in 2007-2008. The test battery included measures of general cognitive ability as well as executive functioning and related abilities. Academic performance was self-reported. RESULTS: With adjustment for sex and age, the VLBW group scored lower or performed slower than the control group in some indices of all tests (these mean differences ranged from 0.3 to 0.5 SD units, p ≤ 0.03) and they had received remedial education at school more frequently; however, no differences existed in self-reported academic performance. The differences were evident in both VLBW-SGA and VLBW-AGA groups. Further covariate adjustments for parental education, current head circumference, and head circumference at birth and, in tests of executive functioning and related abilities, adjustment for IQ estimate had minor effects on the results. CONCLUSIONS: In comparison with control adults, VLBW adults scored lower on several neurocognitive tests. Poorer neurocognitive performance is associated with VLBW irrespective of the intrauterine growth pattern.

Body size at birth and cardiovascular response to and recovery from mental stress in children.

Cardiovascular (CV) response to mental stress, a predictor of CV disease risk, may be determined already in utero. However, the underlying mechanisms remain unclear, and previous studies have used adult subjects and neglected CV recovery. We investigated 147 girls and 136 boys aged 8 years who underwent the Trier Social Stress Test for children to determine whether body size at birth is associated with CV activity. Blood pressure (BP), electrocardiogram and impedance-derived indices were recorded and analyzed from continuous measurements using Vasotrac APM205A and Biopac MP150 systems. Among girls, lower birth weight was associated with lower baseline systolic BP (SBP) and diastolic BP (DBP) values (1.9 mm Hg and 1.5 mm Hg per 1 s.d. birth weight for gestational age, respectively), higher SBP and DBP response to mental stress (1.6 mm Hg and 1.1 mm Hg per 1 s.d. birth weight for gestational age, respectively), slower BP recovery and overall higher cardiac sympathetic activity. In contrast, among boys lower birth weight was associated with higher baseline levels of SBP (2.1 mm Hg per 1 s.d. birth weight for gestational age) and total peripheral resistance (TPR), overall lower cardiac sympathetic activity, lower TPR response to mental stress and a more rapid BP and cardiac sympathetic recovery. In boys, the associations with baseline levels and cardiac sympathetic activity became significant only after adjusting for current body size. These sex-specific results suggest that individual differences in childhood CV response to and recovery from mental stress may have prenatal origins. This phenomenon may be important in linking smaller body size at birth to adult CV disease.

Romantic attachment in young adults with very low birth weight - The Helsinki Study of Very Low Birth Weight Adults.

Early attachment relationships from infancy onward contribute to attachment patterns later in life, to the ability to build up close relationships and to well-being in general. Severely preterm birth may challenge the development of these attachment relationships. We studied whether there are differences in attachment patterns related to romantic relationships between young adults (mean age 22.4 years, s.d. 2.2 years) with very low birth weight (VLBW, <1500 g; n = 162) and their peers born at term (n = 172), who completed the Experiences in Close Relationships Questionnaire - Revised. Young adults born at VLBW showed lower attachment-related anxiety than their peers born at term (mean difference -9.5%, 95% CI -16.0 to -2.6) when adjusted for sex, age, parental education and being in a romantic relationship currently. The groups did not differ in attachment-related avoidance. In subgroup analyses, the VLBW women born small for gestational age (SGA, birth weight <-2 s.d.) scored on average 14.8% (95% CI 3.1-26.6) higher than the control women on attachment avoidance. The effects remained after the exclusion of 18 participants with neurosensory deficits. We found no evidence for a compromised attachment pattern in young adults born at VLBW, with a possible exception of women born SGA at VLBW. VLBW adults were rather characterized by a lower level of attachment-related anxiety.