How Can We Prevent Mother-to-Child Transmission of HTLV-1?

The perception of human T-cell leukemia virus type 1 (HTlV-1) infection as a "silent disease" has recently given way to concern that its presence may be having a variety of effects. HTLV-1 is known to cause adult T-cell leukemia (ATL), an aggressive cancer of peripheral CD4 T cells; however, it is also responsible for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Most patients develop ATL as a result of HTLV-1 mother-to-child transmission. The primary route of mother-to-child transmission is through the mother's milk. In the absence of effective drug therapy, total artificial nutrition such as exclusive formula feeding is a reliable means of preventing mother-to-child transmission after birth, except for a small percentage of prenatal infections. A recent study found that the rate of mother-to-child transmission with short-term breastfeeding (within 90 days) did not exceed that of total artificial nutrition. Because these preventive measures are in exchange for the benefits of breastfeeding, clinical applications of antiretroviral drugs and immunotherapy with vaccines and neutralizing antibodies are urgently needed.

Distribution of serum adiponectin isoforms in pediatric patients with steroid-sensitive nephrotic syndrome.

BACKGROUND: Serum adiponectin circulates in three multimeric isoforms: high-molecular-weight (HMW), middle-molecular-weight (MMW), and low-molecular-weight (LMW) isoforms. Potential change in the circulating adiponectin levels in patients with nephrotic syndrome (NS) remain unknown. This study aimed to assess the levels of total adiponectin and the distribution of its isoforms in pediatric patients with NS. METHODS: We sequentially measured total adiponectin and each adiponectin isoform levels at the onset of NS, initial remission, and during the remission period of the disease in 31 NS patients. We also calculated the ratios of HMW (%HMW), MMW (%MMW), and LMW (%LMW) to total adiponectin incuding 51 control subjects. RESULTS: The median of total serum adiponectin levels in patients were 36.7, 36.7, and 20.2 µg/mL at the onset, at initial remission, and during the remission period of NS, respectively. These values were significantly higher than those in control subjects. The median values of %HMW, %MMW, and %LMW values were 56.9/27.0/14.1 at the onset, 62.0/21.8/13.4 at the initial remission, and 58.1/21.7/17.5 at during the remission period of NS, respectively. Compared with control subjects, %HMW at initial remission and %MMW at the onset were high, and the %LMW values at the onset and at initial remission were low. CONCLUSIONS: In patients with NS, total serum adiponectin levels increase at the onset of the disease, and the ratio of adiponectin isoforms changes during the course of the disease. Further studies are needed to delineate the mechanisms between proteinuria and adiponectin isoforms change.

Issues of infant feeding for postnatal prevention of human T-cell leukemia/lymphoma virus type-1 mother-to-child transmission.

BACKGROUND: Nationwide antenatal human T-cell leukemia/lymphoma virus type-1 (HTLV-1) antibody screening has been conducted in Japan. The purpose of our study was to clarify the issues related to feeding options to prevent postnatal mother-to-child transmission. METHODS: Of the pregnant carriers at 92 facilities in Japan between 2012 and 2015, 735 were followed prospectively. Among the children born to them, 313 (42.6%) children were followed up to the age of 3 and tested for HTLV-1 antibodies. The mother-to-child transmission rate was calculated for each feeding option selected before birth. RESULTS: Among the 313 pregnant carriers, 55.0, 35.1, 6.1, and 3.8% selected short-term breast-feeding (≤3 months), exclusive formula feeding, frozen-thawed breast-milk feeding, and longer-term breast-feeding, respectively. Despite short-term breast-feeding, 8-18% of the mothers continued breast-feeding for 4-6 months. The mother-to-child transmission rate with short-term breast-feeding was 2.3% (4/172), and its risk ratio compared with that of exclusive formula feeding was not significantly different (0.365; 95% CI: 0.116-1.145). Because of the small number of children who were fed by frozen-thawed breast-milk, their mother-to-child transmission rate was not statistically reliable. CONCLUSIONS: Pregnant HTLV-1 carriers tended to select short-term breast-feeding in Japan. While short-term breast-feeding was not always easy to wean within 3 months, it may be a viable option for preventing postnatal mother-to-child transmission because the vertical transmission rate with short-term breast-feeding was not significantly higher than that with exclusive formula feeding. Increasing the follow-up rates for children born to pregnant carriers may provide clearer evidence of preventative effects by short-term breast-feeding and frozen-thawed breast-milk feeding.

Establishment of a novel diagnostic test algorithm for human T-cell leukemia virus type 1 infection with line immunoassay replacement of western blotting: a collaborative study for performance evaluation of diagnostic assays in Japan.

BACKGROUND: The reliable diagnosis of human T-cell leukemia virus type 1 (HTLV-1) infection is important, particularly as it can be vertically transmitted by breast feeding mothers to their infants. However, current diagnosis in Japan requires a confirmatory western blot (WB) test after screening/primary testing for HTLV-1 antibodies, but this test often gives indeterminate results. Thus, this collaborative study evaluated the reliability of diagnostic assays for HTLV-1 infection, including a WB-based one, along with line immunoassay (LIA) as an alternative to WB for confirmatory testing. RESULTS: Using peripheral blood samples from blood donors and pregnant women previously serologically screened and subjected to WB analysis, we analyzed the performances of 10 HTLV-1 antibody assay kits commercially available in Japan. No marked differences in the performances of eight of the screening kits were apparent. However, LIA determined most of the WB-indeterminate samples to be conclusively positive or negative (an 88.0% detection rate). When we also compared the sensitivity to HTLV-1 envelope gp21 with that of other antigens by LIA, the sensitivity to gp21 was the strongest. When we also compared the sensitivity to envelope gp46 by LIA with that of WB, LIA showed stronger sensitivity to gp46 than WB did. These findings indicate that LIA is an alternative confirmatory test to WB analysis without gp21. Therefore, we established a novel diagnostic test algorithm for HTLV-1 infection in Japan, including both the performance of a confirmatory test where LIA replaced WB on primary test-reactive samples and an additional decision based on a standardized nucleic acid detection step (polymerase chain reaction, PCR) on the confirmatory test-indeterminate samples. The final assessment of the clinical usefulness of this algorithm involved performing WB analysis, LIA, and/or PCR in parallel for confirmatory testing of known reactive samples serologically screened at clinical laboratories. Consequently, LIA followed by PCR (LIA/PCR), but neither WB/PCR nor PCR/LIA, was found to be the most reliable diagnostic algorithm. CONCLUSIONS: Because the above results show that our novel algorithm is clinically useful, we propose that it is recommended for solving the aforementioned WB-associated reliability issues and for providing a more rapid and precise diagnosis of HTLV-1 infection.

Correction to: Implementation of nationwide screening of pregnant women for HTLV-1 infection in Japan: analysis of a repeated cross-sectional study.

An amendment to this paper has been published and can be accessed via the original article.

Implementation of nationwide screening of pregnant women for HTLV-1 infection in Japan: analysis of a repeated cross-sectional study.

BACKGROUND: Screening of pregnant women carrying human T-lymphotropic virus type 1 (HTLV-1) has a crucial role in reducing the number of HTLV-1 carriers. A national HTLV-1 screening program for pregnant women was started in 2011 in Japan. The purpose of this study is to report on the implementation of this nationwide screening program. METHODS: This was a retrospective repeated cross-sectional study. We used datasets from surveys of HTLV-1-antibody-positive pregnant women performed by the Japan Association of Obstetricians and Gynecologists in 2011, 2013, and 2016. Outcomes for evaluation included the number of persons (pregnant women) who conducted the screening test, the number of positive persons (women) identified by these tests, and the proportion of positive persons to the number of persons (women) who conducted the tests. RESULTS: Numbers of target facilities changed yearly: 1857 in 2011, 2544 in 2013, and 2376 in 2016. The mean number of screening-test participants increased per facility, but the median increased or decreased. The mean number of positive individuals identified decreased. Multivariate analysis results revealed the number of screenings was slightly reduced yearly, although areas (Kanto and Kinki) and high volume in facility types increased. Regarding the positive rates, some areas (Hokkaido/Tohoku, Kanto, and Chugoku/Shikoku) exhibited decreases or increases by facility type. The number of western blotting (WB) implementations decreased in 2016, positive rates identified by WB decreased in 2016 in all areas, and the number of facility types increased. The number of PCR participants increased in 2016 in Kanto and Kinki, but a decrease in facility type was observed. Positive rates were decreased in all areas (except the central region) but facility types were increased. CONCLUSIONS: The nationwide screening program for HTLV-1 in Japan was almost fully implemented. However, regional variations in screening tests were observed during this implementation. Thus, some incentives are needed to encourage proper implementation across all regions.

Unsupervised breastfeeding was related to sudden unexpected postnatal collapse during early skin-to-skin contact in cerebral palsy cases.

AIM: This study aimed to identify the clinical features of infants who were healthy at birth, but developed sudden unexpected collapse and were then diagnosed with cerebral palsy before 5 years of age. METHODS: We retrospectively analysed 1182 records from the no-fault Japan Obstetric Compensation System for Cerebral Palsy database up to 2016. This identified 45 subjects (3.8%) who were subsequently diagnosed with severe cerebral palsy due to sudden unexpected postnatal collapse (SUPC). They were all healthy at birth, based on the criteria of five-minute Apgar scores of seven or more, with normal umbilical cord blood gases and no need for neonatal resuscitation within five minutes of birth. RESULTS: The median birth weight of the 45 subjects (26 males) was 2770 g (range 2006-3695 g). Of these, 10 developed SUPC during early skin-to-skin contact (SSC). Medical personnel were not present in all 10 cases: nine were being breastfed at the time and eight of the mothers did not notice their infant's abnormal condition until medical staff alerted them. CONCLUSION: This national study of children with cerebral palsy who appeared healthy at birth found that unsupervised breastfeeding was a common factor in cases of SUPC during early SSC.

An 18-Year Follow-up Survey of Dioxin Levels in Human Milk in Japan.

BACKGROUND: Globally, few published studies have tracked the temporal trend of dioxin levels in the human body since 2000. This study describes the annual trend of dioxin levels in human breast milk in Japanese mothers from 1998 through 2015. METHODS: An observational study was conducted from 1998 through 2015. Participants were 1,194 healthy mothers following their first delivery who were recruited annually in Japan. Breast milk samples obtained from participants were analyzed using gas chromatography and mass spectrometry for dioxins, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs). RESULTS: Mean age was 29.5 years, and 53% of participants were 20-25 years old. A declining trend in total dioxin levels was found, from a peak of 20.8 pg toxic equivalence (TEQ)/g fat in 1998 to 7.2 pg TEQ/g fat in 2014. Data from the last 5 years of the study indicated a plateau at minimal levels. In contrast, an increasing trend was found in the mean age of participants during the last 5 years. Although significantly higher dioxin levels were observed in samples from older participants, an upward trend in dioxin levels was not observed, indicating that dietary and environmental exposure to dioxins had greatly diminished in recent years. CONCLUSIONS: Dioxin levels in human breast milk may be approaching a minimum in recent years in Japan. The findings may contribute to global reference levels for environmental pollution of dioxins, which remains a problem for many developing countries.

Body length and occipitofrontal circumference may be good indicators of neurodevelopment in very low birthweight infants - secondary publication.

AIM: The aim of this study was to predict the neurological prognosis of very low birthweight (VLBW) infants. We examined the relationship between nutritional status, brain volume measured by magnetic resonance imaging (MRI) and anthropometric measurements of VLBW infants at term-equivalent age (TEA). METHODS: We evaluated 27 VLBW infants, born at Showa University Hospital in Japan between April 2012 and August 2013, who underwent brain MRI at TEA. Based on their clinical data, we analysed their protein and energy intake. RESULTS: Median values for the 27 VLBW infants were as follows: gestational age, 29.7 weeks; birthweight 1117 g; protein intake 2.7 g/kg/day and energy intake 97.9 kcal/kg/day. At TEA, the standard deviation scores (SDSs) of body weight, body length and the occipitofrontal circumference (OFC) were -0.8, -1.4 and 0.7, respectively. Multiple regression analysis revealed that the SDSs of body length and the OFC at TEA were significant determinants of white matter volume, but that the SDS of body weight at TEA was not. CONCLUSION: Our findings suggest that the SDSs of body length and the OFC at TEA may be better indicators than body weight for predicting the development of the central nervous system in VLBW infants receiving nutritional management.

Proviral Features of Human T Cell Leukemia Virus Type 1 in Carriers with Indeterminate Western Blot Analysis Results.

Western blotting (WB) for human T cell leukemia virus type 1 (HTLV-1) is performed to confirm anti-HTLV-1 antibodies detected at the initial screening of blood donors and in pregnant women. However, the frequent occurrence of indeterminate results is a problem with this test. We therefore assessed the cause of indeterminate WB results by analyzing HTLV-1 provirus genomic sequences. A quantitative PCR assay measuring HTLV-1 provirus in WB-indeterminate samples revealed that the median proviral load was approximately 100-fold lower than that of WB-positive samples (0.01 versus 0.71 copy/100 cells). Phylogenic analysis of the complete HTLV-1 genomes of WB-indeterminate samples did not identify any specific phylogenetic groups. When we analyzed the nucleotide changes in 19 HTLV-1 isolates from WB-indeterminate samples, we identified 135 single nucleotide substitutions, composed of four types, G to A (29%), C to T (19%), T to C (19%), and A to G (16%). In the most frequent G-to-A substitution, 64% occurred at GG dinucleotides, indicating that APOBEC3G is responsible for mutagenesis in WB-indeterminate samples. Moreover, interestingly, five WB-indeterminate isolates had nonsense mutations in Pol and/or Tax, Env, p12, and p30. These findings suggest that WB-indeterminate carriers have low production of viral antigens because of a combination of a low proviral load and mutations in the provirus, which may interfere with host recognition of HTLV-1 antigens.

Efficacy of non-carbapenem antibiotics for pediatric patients with first febrile urinary tract infection due to extended-spectrum beta-lactamase-producing Escherichia coli.

Although carbapenem is the recommended for urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms, non-carbapenems have been reported to be effective for adult patients with UTI caused by ESBL-producing organisms. The purpose of this study was to evaluate the efficacy of non-carbapenems for pediatric patients with UTI due to ESBL-producing Escherichia coli (E. coli) based on the microbiologic and clinical outcomes. Fifteen children, who were treated for first febrile UTI caused by ESBL-producing E. coli were enrolled in this study. Antimicrobial susceptibilities and ESBL production were determined according to the Clinical and Laboratory Standards Institute guidelines. To detect CTX-M genes, polymerase chain reaction was performed with specific primers for blaCTX-M detection. Of the 15 enrolled patients, 10 (66.7%) were boys and 5 (33.3%) were girls, with a median age of four months. VUR was detected in six patients (40%). For detection of blaCTX-M by PCR, CTX-M-3, CTX-M-8, CTX-M-14, and CTX-M-15 were detected in five, one, eight, and one patient, respectively. Overall, 14 of the 15 isolates (93.3%) were susceptible for fosfomycin (FOM), and all isolates were susceptible for cefmetazole (CMZ), flomoxef (FMOX), and imipenem/cilastatin (IPM/CS). Of the 15 patients, 12 (80%) clinically improved without the use of carbapenems. In conclusion, even if isolates of ESBL-producing E. coli are multidrug resistant based on MIC assessment, clinical susceptibility to non-carbapenems, such as CMZ, FMOX, and FOM, is possible. Accordingly, carbapenems may not be required all the time for treatment of pediatric UTI in clinical practice.

PROSPECTIVE MULTICENTER SURVEY ON PREDICTIVE FACTORS FOR POSITIVE ORAL FOOD CHALLENGE TESTS IN DIAGNOSIS OF GASTROINTESTINAL FOOD ALLERGY IN NEONATES.

OBJECTIVE: To assess predictors of positive oral food challenge test (OFC) in neonates that are suggestive of gastrointestinal food allergy. METHODS: A prospective case accumulations study on neonates suspected of having gastrointestinal food allergy was conducted in 126 neonatal intensive care units in Japan between April 2010 and September 2011. Neonates who underwent an OFC for the diagnosis of gastrointestinal food allergy were enrolled. Clinical backgrounds, clinical symptoms, and laboratory findings were compared between neonates with a positive OFC and those with a negative OFC. RESULTS: An analysis was performed in 32 neonates. The OFC results were positive in 9 neonates (28.1%), pseudo-positive in 4, and negative in 19. There were no significant differences in clinical backgrounds between the positive OFC group and the negative OFC group. Vomiting and bloody stool were frequently observed in both groups (approximately 70%), although there were no significant differences in the clinical symptoms between the two groups. Additional diagnostic tests included those for eosinophils in the peripheral blood and stool mucus and allergen-specific lymphocyte stimulation test. There were no significant differences in laboratory findings between the two groups, and many neonates showed pseudo-positive in all of the tests. CONCLUSION: It was difficult to predict OFC results based on clinical symptoms and additional diagnostic test results. In order to obtain an accurate diagnosis of gastrointestinal food allergy in neonates, OFC should be performed proactively under conditions that enable complete understanding of risks to neonates.

Standardization of Quantitative PCR for Human T-Cell Leukemia Virus Type 1 in Japan: a Collaborative Study.

Quantitative PCR (qPCR) analysis of human T-cell leukemia virus type 1 (HTLV-1) was used to assess the amount of HTLV-1 provirus DNA integrated into the genomic DNA of host blood cells. Accumulating evidence indicates that a high proviral load is one of the risk factors for the development of adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. However, interlaboratory variability in qPCR results makes it difficult to assess the differences in reported proviral loads between laboratories. To remedy this situation, we attempted to minimize discrepancies between laboratories through standardization of HTLV-1 qPCR in a collaborative study. TL-Om1 cells that harbor the HTLV-1 provirus were serially diluted with peripheral blood mononuclear cells to prepare a candidate standard. By statistically evaluating the proviral loads of the standard and those determined using in-house qPCR methods at each laboratory, we determined the relative ratios of the measured values in the laboratories to the theoretical values of the TL-Om1 standard. The relative ratios of the laboratories ranged from 0.84 to 4.45. Next, we corrected the proviral loads of the clinical samples from HTLV-1 carriers using the relative ratio. As expected, the overall differences between the laboratories were reduced by half, from 7.4-fold to 3.8-fold on average, after applying the correction. HTLV-1 qPCR can be standardized using TL-Om1 cells as a standard and by determining the relative ratio of the measured to the theoretical standard values in each laboratory.

Renal function in angiotensinogen gene-mutated renal tubular dysgenesis with glomerular cysts.

BACKGROUND: Inherited renal tubular dysgenesis (RTD) is caused by mutations in the genes encoding the components of the renin-angiotensin system (RAS). RTD is characterized by oligohydramnios, renal failure, neonatal hypocalvaria, and severe hypotension. The histological characteristics, underlying mechanism, and long-term prognosis remain poorly known. CASE-DIAGNOSIS/TREATMENT: We describe here a 4-year-old female with RTD. Endocrinologic analysis showed a discrepancy between low plasma renin activity and high active renin concentration, suggesting a loss of the renin substrate, angiotensinogen (AGT). Direct sequencing revealed a frameshift deletion at nucleotide 1,355 in exon 5 in the AGT gene. Although a histological hallmark is regarded to be the absence or poor development of the proximal tubule, the patient does have minimally impaired function of the proximal tubule. Glomerular cysts without glomerular tufts were noted in approximately half of the glomeruli. The urinary concentrating ability and sodium reabsorption and potassium excretion in the distal nephron were severely affected. CONCLUSIONS: The patient has an impaired function of the distal nephron despite minimally affected function of the proximal tubule, probably attributed to renal tubular dysgenesis and fetal hypoperfusion. The renal tubular maturity and the severity of ischemic injury may be key determinants of the clinical symptoms and pathological findings in RTD, in which the RAS plays an important role.

Proteinuria caused by glomerular hypertension during adolescence associated with extremely premature birth: a report of two cases.

BACKGROUND: Prematurity and low birth weight are risk factors for the future development of chronic kidney disease (CKD) and hypertension caused by fewer nephrons with limited filtration surface area. Few reports to date have evaluated their clinical backgrounds and pathological findings, including glomerular hypertension and focal segmental glomerulosclerosis. CASE-DIAGNOSIS/TREATMENT: This report describes two patients, a 15-year-old girl (patient 1), with a birth weight of 618 g and a gestational age of 24 weeks, and a 14-year-old boy (patient 2), with a birth weight of 842 g and a gestational age at 25 weeks. Both had a birth weight appropriate for gestational age. Both were first diagnosed with proteinuria during adolescence, and patient 2 also had hypertension. Pathological findings included glomerulomegaly in both and hypertrophy of the juxtaglomerular apparatus and perihilar glomerulosclerosis in patient 1, suggesting glomerular hypertension. Treatment with lisinopril resulted in the immediate disappearance of proteinuria. Renal dysfunction was observed in both patients, but neither showed evidence of severe aggravation after a follow-up of 5 or 6 years. CONCLUSIONS: Proteinuria in both patients was caused by glomerular hypertension with hyperfiltration. Extremely preterm birth itself may be a risk factor for future CKD. Long-term follow-up of patients born prematurely and at low birth weight, including urinalysis and blood pressure measurements, is necessary to diagnose and treat late renal complications.

Necessity of human milk banking in Japan: Questionnaire survey of neonatologists.

BACKGROUND: If their own mother's milk (OMM) is not available, another mother's milk may be used for extremely low-birthweight (ELBW) infants. Human milk is a bodily fluid, however, therefore we have assumed that other mother's milk is currently seldom given to infants despite its superiority to formula. Although the World Health Organization and the American Academy of Pediatrics have recommended using donor human milk (DHM) from a human milk bank (HMB) in the case that OMM is not available, there is no HMB in Japan. To assess whether other mother's milk is used for ELBW infants and whether an HMB is necessary in Japan, we surveyed neonatal intensive care units (NICU) via questionnaire. METHODS: The questionnaire was sent by email to members of the Japanese Neonatologist Association who are responsible for NICU. RESULTS: In total, 126 completed questionnaires (70.7%) were returned and analyzed. One-fourth of NICU give other mother's milk to ELBW infants. The first choice of nutrition is OMM, but other mother's milk or formula is given to infants at 19% of NICU if OMM is unavailable. Approximately three-fourths of NICU would like an HMB. CONCLUSION: Although human milk contains contagious agents and authorities do not recommend giving other mother's milk as a substitute for OMM, other mother's milk is still a choice in NICU in Japan. Many neonatologists, however, would prefer a safer alternative, that is, DHM obtained from an accredited HMB. A well-regulated HMB should be established and safe DHM should be available for all preterm infants if necessary.

Is fat content of human milk decreased by infusion?

BACKGROUND: Human milk (HM) is the optimum nutrition for preterm infants. Previous studies showed that tube infusion decreased the fat content in thawed HM. The aim of this study was to determine if freezing­thawing is the main reason for decrease of fat content. In neonatal intensive care units, thawed HM is used in general, therefore the aim of this study was to investigate fat loss during tube infusion with regard to changes in tube size, material, and infusion rate. METHODS: First, pre-infusion and post-infusion fat content was measured in 15 fresh HM, 10 thawed HM and 6 formula samples. We compared post-infusion and pre-infusion fat content as well as the percent decrease in fat concentration among fresh HM, thawed HM and formula samples. Second, we measured the fat content of 160 thawed HM samples infused via four different diameters (3­6 Fr), two types of material (DEHP-free and PVC-free), and two infusion rates (30 or 60 min). We compared the percent decrease in fat concentration among four different tube sizes, between DEHP-free and PVC-free tubes, and between 30 and 60 min infusion durations. RESULTS: Post-infusion fat content was significantly decreased compared to before infusion in thawed HM and fresh HM but not in formula. Given that thawed HM resulted in larger decrease in fat content, we performed a second experiment and found no difference regarding differing size, materials or infusion rate. CONCLUSIONS: There was a far greater decrease in the post-infusion fat content of thawed HM compared to fresh HM under all test conditions.

New Japanese neonatal anthropometric charts for gestational age at birth.

BACKGROUND: More than 10 years have passed since the previous Japanese neonatal growth charts were published, therefore the aim of this study was to develop an updated set of Japanese neonatal growth charts. METHODS: We used data from the registry database of the Japan Society of Obstetrics and Gynecology from 2003 until 2005. A total of 150,471 singleton live births without stillbirth or severe congenital malformation were enrolled in the preliminary analysis. It was found that the distribution of the 10th centile charts based on these subjects was skewed toward lower birthweight for preterm infants, because of the significantly lower birthweight in the 10th centile in neonates delivered by cesarean section than those delivered vaginally. Therefore, the data of subjects delivered by cesarean section were also excluded. RESULTS: Finally, 104,748 singleton vaginal births at 22-41 weeks of gestation were used to construct a new set of Japanese neonatal anthropometric charts. The birthweight chart is parity and sex specific. The differences between the Japanese fetal growth chart and the new neonatal birthweight chart were small. CONCLUSION: The present new neonatal anthropometric charts may reveal unrestricted growth pattern mimicking fetal growth. Use of these charts may result in recognition of abnormal fetal growth and risk in preterm infants. Further studies are needed to evaluate the risk for adverse neonatal and long-term outcome among small-for-gestational-age infants using these neonatal charts.

Growth and bone mineralization in small-for-gestational-age preterm infants.

BACKGROUND: Preterm infants are at risk for metabolic bone disease and suboptimal growth. This study examined the hypothesis that, apart from prematurity, intrauterine growth status (expressed as gestational age-specific birthweight standard deviation score) influences bone mineralization and body composition in early infancy. METHODS: In this retrospective study, the groups consisted of preterm small-for-gestational-age (SGA) infants (n = 18; SGA group) and preterm appropriate-for-gestational-age (AGA) infants (n = 24; AGA group). Postnatal bone mineralization was measured at term-adjusted age (postmenstrual age, 37-42 weeks). Bone mineral content (BMC) and body composition were determined on dual-energy X-ray absorptiometry of the whole body. RESULTS: BMC and lean mass were significantly lower in the SGA group than in the AGA group at term-adjusted age (37-42 weeks postmenstrual age). Stepwise regression analysis identified weight at examination as the most significant factor, accounting for 51% of the variance in BMC. CONCLUSION: Bodyweight at term-adjusted age, rather than intrauterine growth, may affect postnatal bone mineralization in preterm low-birthweight infants. Therefore, promoting an increase in body size might increase postnatal bone mineralization in preterm SGA infants.