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.

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.

Small body size at birth and behavioural symptoms of ADHD in children aged five to six years.

BACKGROUND: Behavioural disorders with a neurodevelopmental background, such as attention deficit hyperactivity disorder (ADHD), have been associated with a non-optimal foetal environment, reflected in small body size at birth. However, the evidence stems from highly selected groups with birth outcomes biased towards the extreme low end of the distribution in birth weight. Whether a similar association exists among the normal range of term birth is unclear. METHODS: The ADHD Rating Scale was filled in by the biological mothers and fathers of children aged five to six years who were born healthy at term. Information on weight (kg), height (cm), head circumference (cm), and gestational age at birth were obtained from hospital records, and the ponderal index (kg/m3), a commonly used measure of thinness, and head circumference-to-length ratio were calculated. RESULTS: Behavioural symptoms of ADHD were predicted by a lower ponderal index, a smaller head circumference, and a smaller head circumference-to-length ratio (beta's: -.12 to -.14, p's < .05). Adjustments for length of gestation, mother's age, tobacco and alcohol use during pregnancy, pre-pregnancy body mass index (BMI), or parity, the monthly gross income of the family, child's BMI at the age of five to six years or gender did not change the associations. CONCLUSION: These results suggest that physiological adaptation in utero, indicated by small body size at birth, within term gestational range may increase the susceptibility to behavioural symptoms of ADHD.

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.

Neutrophil CD11b expression and circulating interleukin-8 as diagnostic markers for early-onset neonatal sepsis.

OBJECTIVE: To assess neutrophil CD11b and circulating interleukin 8 (IL-8) as markers of early-onset infection in neonates. METHODS: The study comprised 39 neonates, with a gestational age of 29 to 41 weeks, suspected of infection within 48 hours of life. Neutrophil surface expression of CD11b was quantified with flow cytometry and plasma IL-8 with an enzyme-linked immunosorbent assay. Both data were available from 35 of 39 neonates. Serum C-reactive protein was determined at initial evaluation and, later, on the basis of the clinical picture. Neonates were allocated retrospectively into 2 groups. In the sepsis group (N = 22), 4 had culture-proven sepsis, and 14 had an antenatal risk factor for infection. In the possible-infection group (N = 13), each neonate had a noninfective disorder, but co-occurring infection remained a possibility. Twelve healthy term infants served as controls. RESULTS: CD11b expression and IL-8 levels both increased in order of sepsis > possible infection > healthy. Sensitivity and specificity by the CD11b test for sepsis were equal, at 1.00, and those by the IL-8 test 0.91 and 1.00, respectively; 6 (17.1%) of the 35 neonates had CD11b and IL-8 below cutoff levels. CONCLUSIONS: Measuring neutrophil CD11b expression and circulating IL-8 provides a means to identify early-onset neonatal sepsis. The findings may be helpful in planning strategies to safely reduce the use of antimicrobials in neonates.

Birth outcome in relation to licorice consumption during pregnancy.

A role for glucocorticoids is suspected in the etiology of low birth weight. The authors tested whether maternal consumption of glycyrrhizin (an inhibitor of cortisol metabolism) in licorice affects birth weight in humans. A sample of 1,049 Finnish women and their healthy singleton infants was studied in 1998. Glycyrrhizin intake was calculated from detailed questionnaires on licorice consumption. Glycyrrhizin exposure was grouped into three levels: low (<250 mg/week; n = 751), moderate (250-499 mg/week; n = 145), and heavy (> or =500 mg/week; n = 110). Birth weight and gestational age (from ultrasound measurements) were obtained from hospital records. Babies with heavy exposure to glycyrrhizin were not significantly lighter at birth, but they were significantly more likely to be born earlier: The odds ratio for being born before 38 weeks' gestation was 2.5 (95% confidence interval: 1.1, 5.5; p = 0.03). Although the effect of heavy glycyrrhizin intake on mean duration of gestation was small (2.52 days) when expressed as an effect on the mean, this shift to the left of the distribution of duration of gestation was sufficient to double the risk of being born before 38 weeks. The association remained in multivariate analyses. In conclusion, heavy glycyrrhizin exposure during pregnancy did not significantly affect birth weight or maternal blood pressure, but it was significantly associated with lower gestational age.

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.

Does low IgA in human milk predispose the infant to development of cow's milk allergy?

We sought a relationship between total and cow's milk-specific IgA levels in colostrum and human milk and subsequent development of cow's milk allergy (CMA) in the breast-fed infant. The study included 87 nursing mothers and their infants (age, 2 d to 7 mo), followed prospectively up to 1 y. At 1 y, 48 mothers (69% with an atopic constitution) had an infant with CMA, verified by clinical cow's milk challenge, eight (38% with an atopic constitution) had a baby who had had protracted infantile colic but no CMA (disease control group), and 31 (23% with an atopic constitution) had a healthy infant. Total breast-milk IgA was measured by radial immunodiffusion, and IgA antibodies to cow's milk were measured by ELISA during the breast-feeding period. The levels of total and cow's milk-specific IgA antibodies in colostrum and human milk were significantly lower in the mothers whose baby later developed CMA [estimated third day value, 0.38 g/L (95% confidence interval, 0. 24-0.82)] than in the ones whose infant remained healthy or had had infantile colic but not CMA [0.82 g/L (95% confidence interval, 0. 99-1.51); p < 0.05]. The infants developed CMA significantly more often if the concentration of total IgA antibodies in milk was <0.25 g/L, when measured between 6 d and 4 wk postpartum [sensitivity, 0. 55; specificity, 0.92; odds ratio, 14.7 (95% confidence interval, 3. 1-70.2); p < 0.001]. The levels of cow's milk-specific IgA positively correlated with the levels of total IgA but not with the development of CMA in the infant. The levels of total or cow's milk-specific IgA did not correlate with maternal atopy. IgA antibodies in colostrum and human milk may prevent antigen entry at the intestinal surface of the breast-fed infant. A low IgA content in human milk may lead to defective exclusion of food antigens and thus predispose an offspring to develop food allergies.

Randomized trial comparing natural and synthetic surfactant: increased infection rate after natural surfactant?

The efficacy of a natural porcine surfactant and a synthetic surfactant were compared in a randomized trial. In three neonatal intensive care units, 228 neonates with respiratory distress and a ratio of arterial to alveolar partial pressure of oxygen <0.22 were randomly assigned to receive either Curosurf 100 mgkg-1 or Exosurf Neonatal 5 ml.kg-1. After Curosurf, the fraction of inspired oxygen was lower from 15 min (0.45 +/- 0.22 vs 0.70 +/- 0.22, p = 0.0001) to 6 h (0.48 +/- 0.26 vs 0.64 +/- 0.23, p = 0.0001) and the mean airway pressure was lower at 1 h (8.3 +/- 3.2 mm H20 vs 9.4 +/- 3.1 mm H20, p = 0.01). Thereafter the respiratory parameters were similar. The duration of mechanical ventilation (median 6 vs 5 d) and the duration of oxygen supplementation (median 5 vs 4 d) were similar for Curosurf and Exosurf. After Curosurf, C-reactive protein value over 40 mg l-1 occurred in 45% (vs 12%; RR 3.62, 95%CI 2.12-6.17, p = 0.001), leukopenia in 52% (vs 28%; RR 1.85, 95% CI 1.31-2.61, p = 0.001) and bacteraemia in 11% (vs 4%; RR 3.17, 95% CI 1.05-9.52, p < 0.05). We conclude that when given as rescue therapy Curosurf had no advantage compared with Exosurf in addition to the more effective initial response. Curosurf may increase the risk of infection.

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.

Supplementary feeding in maternity hospitals and the risk of cow's milk allergy: A prospective study of 6209 infants.

BACKGROUND: Early feeding with cow's milk (CM) may increase the risk of cow's milk allergy (CMA). OBJECTIVE: We sought to examine prospectively whether supplementary feeding of CM at the maternity hospital would increase the risk when compared with feeding with pasteurized human milk or hydrolyzed formula. METHODS: We studied 6209 unselected healthy, full-term infants, of whom 5385 (87%) required supplementary milk while in the hospital. The infants were randomly assigned to receive CM formula (1789 infants), pasteurized human milk (1859 infants), or whey hydrolysate formula (1737 infants). The comparison group (824 infants) was composed of infants who were exclusively breast-fed. The infants were followed for 18 to 34 months for symptoms suggestive of CMA. The primary endpoint was a challenge-proven adverse reaction to CM after a successful CM elimination diet. RESULTS: The cumulative incidence of CMA in the infants fed CM was 2.4% compared with 1.7% in the pasteurized human milk group (odds ratio [OR], 0.70; 95% confidence interval [CI], 0. 44-1.12) and 1.5% in the whey hydrolysate group (OR, 0.61; 95% CI, 0. 38-1.00). In the comparison group, CMA developed in 2.1% of the infants. Among the infants who required supplementary feeding at hospital, both exposure to CM while in the hospital (OR, 1.54; 95% CI, 1.04-2.30; P =.03) and obvious parental atopy (OR, 2.32; 95% CI, 1.53-3.52; P <.001) increased the risk of CMA. CONCLUSIONS: Our data indicate that feeding of CM at maternity hospitals increases the risk of CMA when compared with feeding of other supplements, but exclusive breast-feeding does not eliminate the risk.

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.

Idiopathic thrombocytopenic purpura in pregnancy.

OBJECTIVE: The aim of this study was to evaluate retrospectively our strategies in monitoring and treating pregnant women with idiopathic thrombocytopenic purpura (ITP). METHODS: Medical records were reviewed for diagnosis, clinical course, treatment, and neonatal outcome in 35 Finnish women with ITP giving birth to 55 neonates during 53 pregnancies. The outcome of the first (i.e. index) pregnancy was used in the statistical analyses. The platelet immunofluorescence test (PIFT) was used for detection of platelet autoantibodies. The correlation between neonatal platelet counts and results of PIFT was calculated with the Pearson's correlation coefficient and the Fisher's exact test. RESULTS: There were no serious bleeding complications although five of 35 women had platelet counts of less than 50 x 10(9)/l in the third trimester of the index pregnancy. Prophylactic platelet transfusions were given to six of 15 women delivered by cesarean section. Five of 35 (14.3%; 95% confidence interval, 2.6 to 25.8%) neonates had platelet counts of less than 50 x 10(9)/l median 3 days after delivery versus only one of 28 (3.6%; 95% confidence interval, 0.1 to 10.5%) at birth. No infant showed any clinical signs of intracranial hemorrhage. No significant correlation was encountered between neonatal thrombocytopenia and maternal platelet autoantibodies. The history of a previous infant with thrombocytopenia was the only important information in estimating the risk of fetal thrombocytopenia. CONCLUSIONS: To avoid unnecessary and possibly harmful monitoring and treatment, we need further tests for predicting the perinatal risks in pregnant women with ITP.

Is breastfeeding beneficial and maternal smoking harmful to the cognitive development of children?

The effects of breastfeeding on cognitive, visuomotor and language development were examined in healthy children born at full term, after they had reached 56 months of age. Three hundred and sixty-three children were breastfed for less than 5 months, and 363 for 5 months or more. The groups were matched pairwise having regard to maternal education and sex of the child. Significant differences were found in relation to scores reflecting general cognitive capacity, and the results of the visuomotor integration test between children breastfed for less than 5 months and those breastfed for 5 months or more, and between children of mothers who had smoked during pregnancy and non-smoking mothers. In multiple linear regression analysis prolonged breastfeeding was significantly related to scores reflecting general cognitive capacity and results of the visuomotor integration test. However, smoking by mothers during pregnancy was not significantly related to scores in cognitive tests. Biological factors, and factors such as lifestyle and social background, may be more important determinants of a child's development than breastfeeding.

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.