Prenatal and childhood neonicotinoid exposure and neurodevelopment: A study in a young Taiwanese cohort.

Neonicotinoid insecticides (NEOs) dominate the global pesticide market because of their low cost and effectiveness. However, epidemiological studies regarding the potential adverse health effects of exposure to NEOs before birth and in early childhood are limited. Therefore, this study investigated the associations between NEO exposure before birth and during early childhood and neurodevelopment. A total of 273 mother-child pairs were enrolled in this study. Mothers provided urine samples in the third trimester and breast milk during the first and third months of lactation. Their children provided urine samples and were evaluated for neurodevelopment by using the Bayley Scales of Infant and Toddler Development, Third Edition at 2-3 years (N = 96) and the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) at 4-6 years (N = 63). The sum of the concentrations of seven NEOs (ΣNEOs) and the relative potency factor of NEOs, based on comparison with imidacloprid (IMIRPF), were used to assess total exposure to NEOs. Multivariate linear regression analyses were conducted to assess the associations between prenatal and childhood exposure to NEOs and neurodevelopment. The results of the analysis revealed that clothianidin (CLO) and thiamethoxam were the most common NEOs to which children in the Taipei metropolitan area were exposed and that exposure concentrations were high in the Taipei metropolitan area. Imidacloprid was the most frequently detected NEO during the postnatal period. Additionally, exposure to NEOs through breast milk was low. Exposure to CLO, ΣNEOs, and IMIRPF in boys aged 4-6 years was negatively correlated with WPPSI-IV Fluid Reasoning Index. The results of this study indicate that exposure during the third trimester to NEOs does not affect neurodevelopment but that childhood exposure to NEOs may, especially for boys. Further studies with larger sample sizes are required to confirm the sex-specific associations between NEO exposure and neurodevelopment.

Prenatal to preschool exposure of nonylphenol and bisphenol A exposure and neurodevelopment in young children.

BACKGROUND: Nonylphenol (NP) and bisphenol A (BPA) are produced in large quantities worldwide as multipurpose agents. However, studies on relations between NP and BPA exposure and childhood neurodevelopment are few, and the results are inconsistent. This study aimed to investigate associations between prenatal and early childhood NP and BPA exposure and neurodevelopment in mother-child pairs. METHODS: Pregnant women at 27-38 weeks' gestation were recruited, as were children 2-3 years of age (n = 94) and 4-6 years of age (n = 56) years. Urine was collected to assess NP and BPA exposure. Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-III), Wechsler Preschool and Primary Scale of Intelligence (4th edition), and the Full Scale Intelligence Quotient (WPPSI-IV-FSIQ) were used to assess the neurodevelopment of the children. RESULTS: The detection rate and concentration of NP and BPA in the urine of children 4-6 years old were higher than in those 2-3 years old. Children were divided into a high concentration group (3rd tertile) and a reference group (1st and 2nd tertiles) based on natural log-transformed urine concentration of NP and BPA. Girls' Bayley-III motor scores in the high concentration group were higher than those of the BPA reference group of urine of mothers (ß = 6.85, 95% confidence interval [CI]: 1.58-12.13). Boys' FSIQ in the higher concentration group were significantly lower than those in children 2-3 years old in the NP reference group (ß = -11.29, 95% CI: -18.62 to -3.96) (all, p < 0.05). CONCLUSIONS: Prenatal and childhood exposure to NP and BPA may have different effects on the neurodevelopment of young children, and there are no consistent effects between boys and girls.

The Effect of Processing Donor Milk on Its Nutrient and Energy Content.

Background: The pasteurization is a mandatory step to inactivate pathogenic microorganisms of bank milk. For storage, freezing and thawing are necessary. The concentration of macronutrients and energy of bank milk could be influenced by these procedures which are routinely used in human milk bank. Research Aim: The aim of this study is to analyze the effect of bank milk processing (pasteurization and freezing/thawing) on the macronutrients (fat, protein, and carbohydrate) concentration and energy content. Materials and Methods: The samples of donor milk were collected and studied before/after pasteurization and after frozen for 3 months. Total 100 samples of bank milk were tested using an infrared analyzer. The measurements of fat, protein, carbohydrate, and energy were statistically analyzed by SPSS. Results: There was a prominent reduction of fat mean concentration following pasteurization and frozen (20.5% and 6.5%, respectively). The processing did not cause significant changes in protein content, but there were significant increase after pasteurization and decrease after frozen in carbohydrate (p < 0.05). Overall (postpasteurization and frozen storage), a 9.6% decrease was observed for energy content. Conclusion: This study revealed that the processing of bank milk (including Holder Pasteurization and frozen storage) decreased fat and energy content of human milk significantly, and this could not meet the specific needs of preterm infants.

The growth of very-low-birth-weight infants at 5 years old in Taiwan.

BACKGROUND: The goal of this study was to compare the growth and effect of growth on cognitive performance at 5 years of age of a group of very-low-birth-weight (VLBW) infants and a group of healthy full-term infants. METHODS: Beginning in 1995, under the sponsorship of the Premature Baby Foundation, the Society of Neonatology, Taiwan, conducted a multicenter follow-up study of VLBW infants in Taiwan. The study enrolled 322 VLBW infants and 103 controls for assessment of growth data and cognitive performance at several time points from birth through to 5 years of age. Growth data were assessed with measurements of weight, height, and head circumference taken at the ages of 6 months, 12 months, 24 months, and 60 months. Cognitive performance was assessed at the age of 5 years. The VLBW infants were regarded as "failed" if a measurement was 2 standard deviations below the mean measurement of the control group. Neonatal and perinatal data had been collected prospectively as part of a longitudinal study. Cognitive performance was assessed using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R). RESULTS: From 6 months to 5 years, VLBW infants had lower weight, height, and head circumference than the controls. Two hundred twenty-four VLBW infants (69.6%) returned for assessment at 5 years old. Of the 224 VLBW infants, complete sets of measurements of weight, height, and head circumference were obtained for 126 cases (56.3%), 127 cases (56.7%), and 106 cases (47.3%), respectively. Of these, 13 patients (10.3%) failed in weight, 11 patients (8.7%) failed in height, and 17 patients (16.0%) failed in head circumference at the age of 5 years. The mean WPPSI-R scores at the age of 5 years for VLBW children were: 94.1 ± 16.4 (performance IQ), 87.2 ± 12.8 (verbal IQ), and 89.5 ± 14.6 (full IQ). All of these values were also lower than those of the control group, with the differences being statistically significant (p < 0.05). The WPPSI-R scores of VLBW children who failed in head circumference were notably lower than those of VLBW children whose head circumference had caught up with that of their peers. CONCLUSION: The growth of VLBW infants was lower than that of healthy full-term infants through 5 years of age. The cognitive performance for VLBW children was also decreased compared to that of the control group, and there was an association between slower growth and decreased cognitive ability.

Influence of prolonged storage process, pasteurization, and heat treatment on biologically-active human milk proteins.

OBJECTIVES: The bioactive proteins in human milk may be influenced by prolonged storage process, pasteurization, and heat treatment. This study was conducted to evaluate the effects of these procedures. MATERIALS AND METHODS: Three forms of human milk - freshly expressed, frozen at -20°C for a prolonged duration, and pasteurized milk - were collected from 14 healthy lactating mothers and a milk bank. The concentrations of major bioactive proteins (secretory immunoglobulin A, lactoferrin, lysozyme, and leptin) were quantified using enzyme-linked immunosorbent assay kits. Changes in these proteins by heat treatment at 40°C or 60°C for 30 minutes were further evaluated. RESULTS: The mean concentrations of lactoferrin and secretory immunoglobulin A were significantly reduced by 66% and 25.9%, respectively, in pasteurized milk compared with those in freshly-expressed milk. Heat treatment at 40°C or 60°C did not cause significant changes in lactoferrin and secretory immunoglobulin A, but there was an apparent increase in lysozyme (p = 0.016). There were no significant differences in leptin level among these three forms of milk prior to (p = 0.153) or after heat treatment (p = 0.053). CONCLUSION: Various freezing/heating/pasteurization processes applied to human milk prior to delivery to neonates could affect the concentration of immunomodulatory proteins, especially lactoferrin, secretory immunoglobulin A, and lysozyme. Leptin was unaffected by the various handling processes tested. Fresh milk was found to be the best food for neonates. Further studies are warranted to evaluate the functional activity of these proteins and their effects on infants' immunological status.

Characteristics of the first human milk bank in Taiwan.

BACKGROUND: The benefits of feeding human milk to infants, even in prematurity, have been well documented. Well-organized donor milk processing has made the milk bank a good source of nutrition for premature or sick infants if their own mother's milk is not sufficient or suitable. The Taipei City Hospital Milk Bank was established in 2005 and is the first nonprofit human milk bank to operate in Taiwan. METHODS: The milk bank has adopted standards of practice laid down by the Human Milk Banking Association of North America and United Kingdom Association for Milk Banking. The clinical characteristics of the eligible milk donors, the recipients, and the donor milk were reviewed retrospectively. RESULTS: In the past 6 years, 816 eligible donors donated a total or 13,900 L (mean 17.03 L/donor) of breast milk. The mean age of these donors was 31.3 years, and 79.7% of them had college education. Most had term delivery (91.2%), with mean birth weight of their babies being 3120 g; 68.9% of the donors were primiparas. A total of 551 infants had received bank milk, with these indications: prematurity (65.4%), malabsorption (7.6%), feeding intolerance (7.2%), maternal illness (5.1%) and post-surgery (4.6%). The pass rate of raw donor milk was around 72.1%. The most common reasons to discard raw milk were Gram-negative rods contamination (72.8%) and ≥10 colony-forming units/mL of coagulase-negative Staphylococcus (62.3%). Only 0.63% of donor milk post pasteurization showed bacterial growth. CONCLUSION: Proper management and operation of a human milk bank can support breastfeeding, and provide a safe alternative to artificial formula for feeding preterm or ill infants in Taiwan. Sustainability of the milk bank needs more propagation and financial support by health authorities.

The effect of in-hospital developmental care on neonatal morbidity, growth and development of preterm Taiwanese infants: a randomized controlled trial.

INTRODUCTION: Intervention studies of developmental care for preterm infants in Western societies have shown early but unsustainable effects on child outcomes, however only a limited of studies have examined if developmental care interventions produce similar effects in Eastern cultural contexts. AIMS: To examine the effectiveness of in-hospital developmental care on neonatal morbidity, growth and development of preterm infants with very low birth weight (VLBW; birth weight<1500 g) in Taiwan. METHODS: One hundred and seventy-eight VLBW preterm infants were randomly assigned to the clinical trial during hospitalization at three hospitals in Taiwan; the control group received five sessions of standard child-focused developmental care and the intervention group received five sessions of child- and parent-focused developmental care. Sixty-two normal term infants were also included as a comparison group. Infants were examined for morbidity, growth and developmental outcomes at term age. RESULTS: At study entry, more infants in the intervention group were twins or multiples than those in the control group (29% vs. 16%, p=0.05). After adjusting for birth set, the intervention group had lower incidences of stage II-III retinopathy (odds ratio [OR]=0.34 [95% confidence interval (CI): 0.15-0.79]; p=0.01) and feeding desaturation (OR=0.32 [95% CI: 0.10-1.00]; p=0.05) and had greater daily weight gains (difference=2.0 g/day [95% CI: 0-4.0 g/day]; p=0.05) as compared with the control group. However, the intervention and control groups did not differ in any of the neurodevelopmental measures. CONCLUSIONS: In-hospital developmental care has short-term benefits for Taiwanese VLBW preterm infants in reducing the risk of retinopathy and feeding desaturation as well as in enhancing weight gains at term age.

Surfactant lavage decreases systemic interleukin-1 beta production in meconium aspiration syndrome.

BACKGROUND: Surfactant lavage has been used to remove meconium debris in meconium aspiration syndrome (MAS), but the influence of surfactant lavage on pro-inflammatory cytokines and cellular apoptosis is unclear. The aim of this study was to investigate the response of pro-inflammatory cytokine and the influence on alveolar cellular apoptosis using therapeutic bronchoalveolar lavage with diluted surfactant to treat MAS. METHODS: Twelve newborn piglets were anesthetized, intubated via tracheostomy, and artificially ventilated. MAS was induced by intratracheal instillation of 3-5 mL/kg of 20% human meconium. The piglets were then randomly assigned to a surfactant lavage group (n= 6) or a control group (n= 6). Piglets in the lavage group received bronchoalveolar lavage with 30 mL/kg diluted surfactant (5 mg/mL) in two aliquots. Cardiopulmonary parameters were monitored continuously. Serum was obtained hourly to measure concentrations of pro-inflammatory cytokines, including interleukin (IL)-I beta, IL-6, and tumor necrosis factor alpha. Lung tissue was histologically examined after experiments, and terminal deoxynucleotidyl transferase-mediated nick-end labeling assay for apoptotic cell death was also performed. RESULTS: The animals in the lavage group displayed significantly better gas exchange and lower serum concentrations of IL-1 beta than the animals in the control group (P < 0.05). The number of apoptotic cells in lung tissues was significantly lower in the lavage group than the control group, and also in the nondependent than the dependent site. CONCLUSION: Therapeutic surfactant lavage improves oxygenation, decreases production of systemic pro-inflammatory cytokine IL-1 beta, and alleviates the severity of lung cell apoptosis in newborn piglets with experimentally-induced MAS.

Cognitive development at age 8 years in very low birth weight children in Taiwan.

BACKGROUND/PURPOSE: All children should have some developmental screening periodically throughout childhood, especially those who were born prematurely. There is limited information about the development of children with very low birth weight (VLBW; birth weight < 1500 g) beyond the preschool age in Taiwan. We evaluated intelligence quotient (IQ) and cognitive ability of prematurely born school-aged children in Taiwan. METHODS: This was a multicenter study of VLBW and full-term children born between 1995 and 1997 at four hospitals in northern Taiwan. We used the Wechsler Intelligence Scale for Children, 3rd Edition (WISC-III), to assess these children. Demographic data were recorded including maternal and paternal age, education, birth weight, gestational age, and gender. RESULTS: A total of 189 children (130 with VLBW born prematurely and 59 born at full term) were recruited. There were significant differences in performance IQ (PIQ; 90.16 +/- 17.05 vs. 108.51 +/- 15.65, p < 0.001), verbal IQ (VIQ; 97.43 +/- 15.62 vs. 111.78 +/- 13.65, p < 0.001), full-scale IQ (FSIQ; 93.14 +/- 16.33 vs. 111.05 +/- 14.81, p < 0.001), verbal comprehension index score (VCIS; 98.06 +/- 15.53 vs. 112.47 +/- 13.74, p < 0.001), perceptional organization index score (POIS; 92.39 +/- 17.13 vs. 109.42 +/- 14.87, p < 0.001) and freedom from distractibility index score (FDIS; 98.34 +/- 17.71 vs. 110.53 +/- 10.94, p = 0.008). There was no correlation between perinatal outcomes and FSIQ. CONCLUSION: Our results suggest that VLBW children have significantly lower PIQ, VIQ, FSIQ, VCIS, POIS and FDIS at primary school compared with full-term children.

Brief report: Taiwanese infants' mental and motor development--6-24 months.

OBJECTIVES: To establish the normative data of the Bayley Scales of Infant Development-Second Edition (BSID-II) on Taiwanese infants from age 6 to 24 months and to explore the factors that relate to their mental and motor development. METHODS: Five hundred and seven Taiwanese full-term infants were prospectively examined with the BSID-II at 6, 12, 18, and 24 months of age. RESULTS: Taiwanese infants' Bayley mental and motor raw scores were lower than the United States norms from age 6 to 24 months, however, the discrepancy gradually declined with increasing age. Gender, intrauterine growth status, birth order, region of residence, maternal education, and paternal occupation were shown to have longitudinal associations with their mental and/or motor scores. CONCLUSIONS: Differences existed in the mental and motor development among Taiwanese and American infants. Our preliminary norms of the BSID-II may be more appropriate than the United States norms for Taiwanese children.

Factors affecting the non-compliance for follow-up in very low birth weight children.

BACKGROUND: Long-term longitudinal follow up of very low birth weight (VLBW, birth weight < or =1500 g) infants is important. This study assessed the factors affecting non-compliance for follow-up at different ages in VLBW children. METHODS: The demographic data, morbidity and neurodevelopmental data of 321 VLBW infants were analyzed between those returned and not returned. RESULTS: The majority of the children who did not attend the follow-up clinic were caused by inaccessibility, and refusal by the parents. The non-compliant children had higher rate of multiple births, short paternal education years, mother being a housewife, and lower incidence of first child, emergent caesarian section and small for gestational age. They did not differ much from the children returned in the occurrence of neonatal diseases. No significant difference of the growth and neurodevelopmental status at the previous visit could be observed between children of the two groups. When data of different follow-up visits were compared, it was noted that the most common reason for not attending the follow-up visits was inaccessibility for the 6- and 12-month visits and refusal by the parents for other visits. Multivariate logistic regression analysis revealed that variable(s) increasing the non-compliance were none for the 6-month visit, severe retinopathy of prematurity for the 12-month visit, short duration of paternal education for the 18-, 24- and 36-month visits and multiple births for the 36-month visit. CONCLUSIONS: These results showed that the reasons and the affecting variables for not attending the follow-up assessment were different for different age groups.

Prognostic predictors of neurodevelopmental outcome or mortality in very-low-birth-weight infants.

Survival rate of very-low-birth-weight (VLBW) infants has much improved in recent years. However, neurodevelopmental outcomes are still of the most concerned to such infants' parents. In order to survey survival rate, neurodevelopmental outcome and prognostic factors in these infants, we did a retrospective study of VLBW infants who were admitted to neonatal intensive care unit of Taipei City Hospital, Branch for Women and Children from 1st January 2001 to 31th October 2004. We reviewed their medical records and analyzed the data. A total of 68 cases were enrolled in this study, and overall one-year survival rate was 70.3% (45/64). The unfavorable outcome group had lower birth weight, lower gestational age, lower Apgar scores at 1-minute and 5-minute, higher rate of vaginal delivery, more respiratory distress syndrome (RDS), and higher IVH grades (all p value < 0.05). However, with multiple logistic regression analysis, only low birth weight and higher IVH grades were the significant predictors of unfavorable outcome. Univariate analysis showed that RDS increased but Cesarean section (C/S) decreased the risk of severe IVH. According to the result, we can make the conclusion that the survival rate of VLBW infants in our hospital was similar to that in other medical centers in Taiwan. In order to prevent severe grades of IVH and subsequent unfavorable outcome in VLBW infants, prenatal therapies to prevent RDS and perhaps choice of C/S as delivery mode are the best strategies.

Delivery before 32 weeks of gestation for maternal pre-eclampsia: neonatal outcome and 2-year developmental outcome.

BACKGROUND AND OBJECTIVE: In the literature, there are conflicting data on the neonatal outcome in preterm infants who were delivered for maternal pre-eclampsia. The purpose of this study is to investigate the effect of maternal pre-eclampsia on neonatal morbidity and 2-year developmental outcome in a population of preterm infants delivered before 32 weeks of gestation. METHODS: The hospital records of all 89 surviving VLBW infants with GA below 32 weeks born from January 1997 to December 1999 were reviewed retrospectively. Data on respiratory outcome, sepsis and intraventricular hemorrhage (IVH) were compiled and analyzed for their association to maternal pre-eclampsia. Seventy-eight infants were assessed employing the Bayley Scales of Infant Development for developmental outcome at 2 years of corrected age. RESULTS: There was no difference in neonatal morbidity between groups. More infants born to pre-eclamptic mothers had lower MDI scores at 24 months of age (P=0.04) as compared to infants without maternal pre-eclampsia. After multiple logistic regression analysis, pre-eclampsia (P=0.007, OR=10.8) remained a significant risk factor of mildly delayed MDI at 24 months of age. CONCLUSION: Delivery before 32 weeks because of pre-eclampsia was associated with an increased risk of poor cognitive outcome. There was no significant difference in the postnatal course in comparison with infants born after pregnancies not complicated by pre-eclampsia.