Holiday effect on childbirth: A population-based analysis of 21,869,652 birth records, 1979-2018.

Maternity and neonatal services always have to operate 24 hours a day and 7 days a week, and require well preparedness to guarantee safe deliveries for both mothers and babies. However, the evidence of holiday effect from large-scale data is still insufficient from the obstetrics perspective. We analyzed data of over 21 million births in Japan from January 1, 1979, to December 31, 2018. We revealed that the number of births is lower on holidays, and especially among high-risk births such as low birthweight and preterm births. The frequency of high-risk birth has been increasing over the study period, and the variation by the day of week and between holiday and non-holiday have become more prevalent in recent years.

The impact of cyclooxygenase inhibitor use on urinary prostaglandin metabolites in preterm infants.

BACKGROUND: There is limited evidence on the association between the clinical course of patent ductus arteriosus (PDA) and prostaglandin (PG) metabolites. This study aimed to determine the influence of PDA treatment on urinary PG metabolite excretion in very-low-birth-weight (VLBW) infants. METHODS: Urine samples were collected from 25 VLBW infants at 1, 3, and 7 days of age. Infants were separated into two groups: a PDA-treated group that received a cyclooxygenase-2 (COX) inhibitor (n = 12) and a control group that did not receive a COX inhibitor during the first 7 days after birth (n = 13). Urinary PG metabolite tetranor prostaglandin E2 metabolite (t-PGEM) and tetranor prostaglandin D2 metabolite (t-PGDM) levels were analyzed using liquid chromatography-tandem mass spectrometry. RESULTS: Urinary t-PGEM excretion levels were not significantly different between the groups at 1, 3, and 7 days of age. Urinary t-PGDM excretion levels at 1 day of age were higher in PDA-treated infants than in control infants (median [interquartile range]: 5.5 [2.6, 12.2] versus 2.1 [1.0, 3.9] ng/mg creatinine; p = 0.017); however, among PDA-treated infants, the levels were significantly lower at 3 and 7 days than at 1 day of age (5.5 [2.6, 12.2] versus 3.4 [1.7, 4.5] and 4.0 [1.7, 5.3] ng/mg creatinine, respectively; p < 0.05). The urinary t-PGDM excretion level in the control group did not significantly differ among the time points. CONCLUSION: PDA and COX inhibitor administration affected PG metabolism in VLBW infants. Our results indicated that urinary t-PGDM excretion was significantly associated with PDA-treatment in preterm infants.

The head circumference to chest circumference ratio provided an easy way to detect foetal growth restriction in term infants.

AIM: The head circumference to chest circumference (HC/CC) ratio has been used to identify low birth weight infants in developed countries. This study was conducted to examine whether the ratio could distinguish asymmetrical foetal growth restriction (FGR). METHODS: This retrospective observational study was conducted with 1955 infants (50.5% male) born at term between 2016 and 2020 at Tokyo Metropolitan Toshima Hospital, Japan. RESULTS: We found that 120 (6.1%) had FGR. Their mean birth weight was 3052.1 ± 367.3 g, and their mean gestational age was 39.1 ± 1.1 weeks. Logistic regression analysis showed that the association between the HC/CC ratio and FGR had a regression coefficient of -20.6 (p < 0.000). The linear regression analysis showed that the association between the HC/CC ratio and the birth weight z-score had a regression coefficient of -8.59 (p < 0.000). The coefficient of correlation was -0.33 (p < 0.001). The receiver operating characteristic curve for detecting FGR showed that the area under the curve was 0.75 and the cut-off value was 0.93, with sensitivity of 75.8% and specificity of 60.8%. CONCLUSION: Our study established the associations between HC/CC ratio and FGR and birth weight z-scores and confirmed that the ratio provided an easy way to detect FGR in term-born infants.

High number of seizures and unconsciousness in patients with SARS-CoV-2 omicron variants: a retrospective study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variants are now a pandemic. There are differences in clinical features in SARS-CoV-2 variants and we conducted this study to assess the clinical features of coronavirus disease (COVID-19) in children with SARS-CoV-2 omicron variants. The study included children with COVID-19 arrivedto Tokyo Metropolitan Toshima Hospital between January 2020 and October 2022. The clinical features of 214 children with SARS-CoV-2 non-omicron variants and 557 children with omicron variants were compared. In the SARS-CoV-2 omicron variant group, more patients had fever, sore throat, nausea and/or vomiting, and seizures and/or disorders of consciousness. In SARS-CoV-2 non-omicron variants, there was only one patient with seizure and/or unconsciousness whereas there were 92 children in omicron variants. Among these 92 patients, 46 (49%) were diagnosed with simple febrile seizures; 23 (25%), with complex febrile seizures; 10 (11%) with status epilepticus; and two (2%) with encephalopathy. Their mean age was 4.0 ± 3.0 years-a wider age distribution than that in other febrile seizures but similar to that in febrile seizures in patients with influenza. SARS-CoV-2 omicron variants are likely to cause seizures and unconsciousness in children and their age distribution was wider than other febrile seizures patients but similar to those in influenza patients. In clinical practice in patients with COVID-19 and influenza, clinicians should be aware of these features.

Evaluation of the transmission of SARS-CoV-2 through breast milk: a case series.

Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through breast milk remains controversial. This study aimed to determine the presence of SARS-CoV-2 in breast milk and assess its transmissibility to the child in infancy. Eleven samples were obtained from nine mothers with coronavirus disease 2019 (COVID-19). All but one sample had negative results on a reverse transcription-quantitative polymerase chain reaction. Among nine children, five were diagnosed with COVID-19, including one child whose mother's milk tested positive. Although SARS-CoV-2 RNA was detected in breast milk, its possible transmission via breastfeeding could not be established. Thus, we conclude that the physical attachment between mother and child is a conceivable transmission route.

Low billing rates for pediatric sedation fee on magnetic resonance imaging.

BACKGROUND: The 2018 revision of social insurance in Japan allows additional fees to be calculated for pediatric magnetic resonance imaging (MRI) that must be performed under sedation. The number and trend of actual claims since this revision was established is unknown. The aim of this study to investigate the use of the additional fees and any regional differences in the use. METHODS: To analyze the claims of additional fees for pediatric sedated MRI after the fiscal year (FY) 2018, the actual claims in inpatient and outpatient practice was analyzed using publicly-available data from the Ministry of Health, Labour and Welfare (MHLW). We analyzed the calculation rate for all MRI scans. Annual changes in the actual number and calculation rate were analyzed. The ratio of the number of additional fees to the overall number of pediatric radiological procedures was used to examine the geographic disparity. RESULTS: The number of calculations from FY 2018 to FY 2020 was available. In FY 2020, only 1347 additional fees were calculated, corresponding to 0.35% of the total number of MRI scans. The number of fees showed a decreasing trend. Most cases were in the 0-4 year age group; however, there were a few cases in the 10-14 year age group without such a decrease. The relative number of calculations by prefecture showed an up to 14-fold disparity. CONCLUSIONS: The requirements for sedation for pediatric MRI are strict, but they are not fully utilized. Measures such as relaxing the requirements for the fee are needed to make MRI-related sedation safer.

Skeletal Muscle Insulin Resistance in a Novel Fetal Growth Restriction Model.

The abnormal fetal environment exerts long-term effects on skeletal muscle, and fetal growth restriction (FGR) is associated with insulin resistance in adulthood. In this study, we examined insulin resistance in early adulthood and insulin signaling in skeletal muscle using a novel FGR rat model. Ameroid constrictors (AC) were placed on the bilateral uterine and ovarian arteries of rats on day 17 of gestation; placebo surgery was performed on the control group. We measured body weight at birth, 4, 8, and 12 weeks of age and performed oral glucose tolerance tests at 8 and 12 weeks. Rats were dissected at 12 weeks of age. We examined the mRNA and protein expression of insulin signaling pathway molecules in skeletal muscle. FGR rats had a significantly lower birth weight than control rats (p = 0.002). At 12 weeks of age, the incremental area under the curve of blood glucose was significantly higher, and GLUT4 mRNA and protein expression in soleus muscle was significantly lower in the FGR group than in the control group. Reduced placental blood flow in the AC-attached FGR group caused insulin resistance and altered insulin signaling in skeletal muscles. Therefore, FGR causes skeletal muscle insulin resistance in early adulthood.

Detecting geographical clusters of low birth weight and/or preterm birth in Japan.

In Japan, mean birth weight has significantly decreased from 3152 g in 1979 to 3018 g in 2010 and the prevalence of preterm birth (PTB) has risen to 5.7% in the last thirty years. However, the presence and magnitude of geographical differences in low birthweight (LBW) and/or PTB in Japan is not well understood. We implemented spatial analysis to identify localized clusters and hot spots of LBW and/or PTB during 2012-2016. The Japan national birth database was used in this study. A total of 5,041,685 (male: 2,587,415, female: 2,454,270) births were used for spatial analysis using empirical Bayes estimates of the incidence rate of LBW and/or PTB and spatial scan tests to detect hot-spot areas with p values calculated from Monte Carlo iterations. The most and second likely clusters were located in two areas: (1) the small islands in south-west Japan (Amami and Okinawa, Relative risk = 1.09-1.67 with p < 0.001) and (2) the cities on the base of Mt. Fuji, stretching over three neighboring prefectures of Yamanashi, Shizuoka and Kanagawa (Relative risk = 1.10-1.55 with p < 0.001), respectively. We need to optimize the medical resource allocations based on the evidence in geographical clustering of LBW and/or PTB at specific locations in Japan.

Use of Head and Chest Circumference Ratio as an Index of Fetal Growth Retardation in Preterm Infants.

We evaluated the relationship between fetal growth in preterm babies using the head circumference (HC)/chest circumference (CC) ratio and other anthropometric parameters at birth and at school age. Data were collected from 187 very low birth weight (VLBW) children born at less than 30 weeks of gestational age (GA) at birth and at 6 years. We assessed the correlation between the HC/CC ratio and body weight (BW), body length (BL), and HC z-scores at birth, and BW, body height (BH), and body mass index (BMI) z-scores at 6 years. Multiple regression analysis showed that BW z-score, BL z-score, and HC z-score at birth were significantly associated with HC/CC at birth. The BMI z-score at 6 years was also significantly associated with HC/CC at birth. The HC/CC ratio at birth is a reliable parameter for evaluating fetal growth restriction and a possible predictor of physical growth in VLBW children.

Case report: Mild encephalitis with a reversible splenial lesion associated with SARS-CoV-2 infection in a patient with MYRF variant.

We report a 14-year-old girl with a heterozygous p. Gln403Arg variant in the MYRF gene, who had five episodes of encephalopathy. She experienced reduced consciousness, numbness in the arm, and impaired verbal communication from day 4 of SARS-CoV-2 infection. Magnetic resonance imaging of her head showed reduced water diffusion in the corpus callosum and deep white matter. These features were similar to those seen in her previous episodes of encephalopathy. She was treated with methylprednisolone pulse therapy and recovered completely within a week.

Growth Trajectories during the First 6 Years in Survivors Born at Less Than 25 Weeks of Gestation Compared with Those between 25 and 29 Weeks.

We aimed to determine the differences in the growth trajectories of the youngest gestational survivors (<25 weeks' gestation) up to 6 years of age compared to those of older gestational ages. Preterm infants were divided into two groups: 22−24 weeks' gestation (male (M) 16, female (F) 28) and 25−29 weeks' gestation (M 84, F 59). Z-scores of body weight (BW), body length (BL), and body mass index (BMI) were derived from Japanese standards at 1, 1.5, 3, and 6 years of corrected age. Comparisons between the two groups by sex were made using the Wilcoxon test and linear regression analysis to examine the longitudinal and time-point associations of anthropometric z-scores, the presence of small for gestational age (SGA), and the two gestational groups. BW, BL, BMI, and z-scores were significantly lower in the 22−24 weeks group at almost all assessment points. However, there were no significant differences in BW, BL, BMI, and z-scores between the two female groups after 3 years. BMI z-scores were significantly associated with the youngest gestational age and the presence of SGA at all ages in males, but not in females. The youngest gestational age had a greater influence in males on the z-score of anthropometric parameters up to 6 years of age.

Associations between size at birth and size at 6 years among preterm infants: a retrospective cohort study.

BACKGROUND: Little is known about the relationship between fetal growth and size at school age in children born prematurely. We evaluated the relationships between gestational age and anthropometric z-scores at birth and size at 6 years of age in very-low-birthweight infants born at <30 weeks' gestation. METHODS: We collected data from the medical records of 187 preterm children at birth and 6 years of age. We evaluated correlations between gestational age and z-scores for weight, body length, and head circumference at birth and z-scores for weight, height, and body mass index at 6 years of age. RESULTS: Simple regression analysis showed that, in boys and the overall group, gestational age and z-scores for weight, body length, and head circumference at birth had significant association with z-scores for weight, height, and body mass index at 6 years of age. No significant associations were found in girls, except for weight z-scores at 6 years with gestational age and head circumference z-scores at birth. Multiple regression analysis showed that gestational age and length z-score at birth were significantly and independently associated with weight and height z-score at 6 years. Gestational age was also significantly and independently associated with body mass index z-score at 6 years. CONCLUSION: Gestational age and fetal growth in length (assessed with the birth-length z-score) were associated with anthropometric z-scores at 6 years in very-low-birthweight children born at <30 weeks of gestation, especially in boys.

Hydrogen-rich water reduced oxidative stress and renal fibrosis in rats with unilateral ureteral obstruction.

BACKGROUND: Congenital obstructive nephropathy (CKD) is commonly implicated in the pathophysiology of chronic kidney disease occurring in the pediatric and adolescent age groups and the release of reactive oxygen species contribute to the worsening of renal fibrosis. Molecular hydrogen (H2) protects against tissue injury by reducing oxidative stress. We evaluated the efficacy of oral H2-rich water (HW) intake in preventing unilateral ureteral obstruction (UUO)-induced renal injury in rats. METHODS: Male Sprague-Dawley UUO or control rats were administered with distilled water (DW) or HW for 2 weeks post-surgery. Histopathological and immunohistochemical analyses of kidney samples were performed. RESULTS: Histological changes were not apparent in the sham-operated kidneys. However, UUO kidneys were found to have widened interstitial spaces and tubular dilatation. Compared with the UUO + DW group, HW administration attenuated tubulointerstitial injury and reduced interstitial fibrotic area, causing a substantial decline in the frequency of α-SMA-, ED-1-, and TGF-ß1-positive cells in the UUO + HW group. The decrease in the klotho mRNA expression in the UUO + HW group was less pronounced than that in the UUO + DW group. CONCLUSION: Oral HW intake reduced oxidative stress and prevented interstitial fibrosis in UUO kidneys, potentially involving klotho in the underlying mechanism. IMPACT: Oral intake of hydrogen-rich water (HW) can reduce oxidative stress and suppress interstitial fibrosis in unilateral ureteral obstruction-induced renal injury in rats. This mechanism possibly involves klotho, which is known for its antiaging roles. The association between molecular hydrogen and klotho in renal fibrosis is well known; this is the first report on the association in a unilateral ureteral obstruction model. Drinking HW is a safe and convenient treatment for oxidative stress-induced pathologies, without side effects. As a prospect for future research, oral HW intake to treat oxidative stress may improve renal fibrosis in congenital obstructive nephropathy.

Analysis of Factors Associated With Body Mass Index at Ages 18 and 36 Months Among Infants Born Extremely Preterm.

Importance: The development of neonatology has been associated with improved survival among infants born extremely preterm, and understanding their long-term outcomes is becoming increasingly important. However, there is little information on body mass index (BMI) among these children. Objective: To determine factors associated with BMI at ages 18 months and 36 months among infants born extremely preterm. Design, Setting, and Participants: This retrospective, multicenter cohort study was conducted using data from the Neonatal Research Network Japan database for 8838 infants born at gestational ages 23 to 28 weeks with data on BMI at 18 months and 36 months. Data were analyzed from April 2018 through June 2021. Exposures: BMI and BMI z score at ages 18 months and 36 months were regressed with gestational age, intrauterine growth restriction (IUGR) status, and complications during pregnancy and the neonatal period separately by presence of multiple pregnancy and sex. Main Outcomes and Measures: BMI and BMI z score at ages 18 months and 36 months. Results: Among 16 791 eligible infants born extremely preterm, 8838 infants were included in the analysis. There were 7089 infants born from single pregnancies (mean [SD] gestational age, 26.0 [1.6] weeks; 3769 [53.2%] boys; mean [SD] birth weight, 847 [228] g) and 1749 infants born from multiple pregnancies (mean [SD] gestational age, 26.3 [1.5] weeks; 903 [51.6%] boys; mean [SD] birth weight, 860 [217] g). In single pregnancies, every week of increased gestational age was associated with an increase in BMI of 0.21 (95% CI, 0.17-0.25) among boys and 0.20 (95% CI, 0.15-0.25) among girls at age 18 months and 0.21 (95% CI, 0.18-0.24) among boys and 0.21 (95% CI, 0.18-0.24) among girls at age 36 months. There was an interaction association between gestational age and IUGR among boys at age 36 months, with a decrease in the change associated with gestational age of 0.12 (95% CI, 0.05-0.19). Every week of increased gestational age in single pregnancies was associated with an increase in BMI z score of 0.14 (95% CI, 0.17-0.21) among boys and 0.17 (95% CI, 0.13-0.21) among girls at age 18 months and 0.19 (95% CI, 0.16-0.22) among boys and 0.17 (95% CI, 0.15-0.20) among girls at age 36 months. Among single pregnancies, IUGR was associated with a decrease in BMI among boys (0.59 [95% CI, 0.23-0.95]) and girls (0.75 [95% CI, 0.39-1.11]) and BMI z score among boys 0.85 [95% CI, 0.25-0.95)] and girls (0.67 [95% CI, 0.36-0.97] at age 18 months and BMI among boys (0.44 [95% CI, 0.17-0.18]) and girls (0.84 [95% CI, 0.55-1.12]) and BMI z score among boys (0.46 [95% CI, 0.21-0.71]) and girls (0.77 [95% CI, 0.53-1.01]) at age 36 months. In multiple pregnancies, IUGR was associated with a decrease in BMI z score at age 36 months among boys (0.26 [95% CI, 0.42-0.89]) and girls (0.29 [95% CI, 0.22-0.79]). In single pregnancies intraventricular hemorrhage (IVH) was associated with a decrease in BMI of 0.47 (95% CI, 0.21-0.73) among boys and 0.42 (95% CI, 0.13-0.71) among girls at age 18 months and 0.53 (95% CI, 0.32-0.74) among boys and 0.31 (95% CI, 0.07-0.54) among girls at age 36 months. IVH was associated with a decrease in BMI z score in single pregnancies of 0.63 (95% CI, 0.20-0.41) among boys and 0.35 (95% CI, 0.12-0.60) among girls at age 18 months and 0.53 (95% CI, 0.34-0.71) among boys and 0.30 (95% CI, 0.11-0.50) among girls at age 36 months. Similar associations were seen in multiple pregnancies. Conclusions and Relevance: This study found that gestational age, the presence of IUGR and multiple pregnancy, and IVH complications were associated with infant BMI at ages 18 months and 36 months. These findings suggest that these complicating factors should be considered when setting growth targets and nutrition strategies for infants born extremely preterm.

Impact of domestic travel restrictions on transmission of COVID-19 infection using public transportation network approach.

The international spread of COVID-19 infection has attracted global attention, but the impact of local or domestic travel restriction on public transportation network remains unclear. Passenger volume data for the domestic public transportation network in Japan and the time at which the first confirmed COVID-19 case was observed in each prefecture were extracted from public data sources. A survival approach in which a hazard was modeled as a function of the closeness centrality on the network was utilized to estimate the risk of importation of COVID-19 in each prefecture. A total of 46 prefectures with imported cases were identified. Hypothetical scenario analyses indicated that both strategies of locking down the metropolitan areas and restricting domestic airline travel would be equally effective in reducing the risk of importation of COVID-19. While caution is necessary that the data were limited to June 2020 when the pandemic was in its initial stage and that no other virus spreading routes have been considered, domestic travel restrictions were effective to prevent the spread of COVID-19 on public transportation network in Japan. Instead of lockdown that might seriously damage the economy, milder travel restrictions could have the similar impact on controlling the domestic transmission of COVID-19.

Urinary angiotensinogen in pediatric urinary tract infection.

BACKGROUND: Urinary tract infection (UTI) is one of the most common diseases in children, and urinary angiotensinogen (U-AGT) is a new biomarker gathering attention in many renal diseases. U-AGT reflects intrarenal renin-angiotensin system (RAS) activity. We conducted a study to measure U-AGT in children <4 months old with UTI. METHODS: All children <4 months old who came to Toshima Hospital with fever between January 2015 and December 2015 were included. Patients were divided into a UTI group and a non-UTI group, and U-AGT was measured. RESULTS: Median U-AGT was higher in patients with UTI compared with patients without UTI: (0.56 ng/dL, range, 0.025-2.753 ng/dL vs 0.13 ng/dL, range, 0.008-1.697 ng/dL, respectively; P < 0.05). CONCLUSIONS: U-AGT is elevated in UTI patients, and RAS activation may contribute to renal injury caused by UTI.

Long-term renal tubular damage in intrauterine growth-restricted rats.

BACKGROUND: Intrauterine growth restriction (IUGR) has been shown to be associated with increased risk of renal disease or hypertension in later life. Glomerular dysfunction, however, has mainly been reported, and limited information is available to link IUGR with renal tubular damage. The aim of this study was therefore to investigate urinary markers of tubular damage in a rat model of IUGR induced by bilateral uterine artery ligation. METHODS: Pregnant Sprague-Dawley rats underwent bilateral uterine artery ligation, while the control group underwent sham surgery. RESULTS: Birthweight was reduced, and urinary ß2-microglobulin (ß2-MG)-, cystatin C (Cys-C)-, and calbindin-to-creatinine ratios were significantly higher at weeks 4 and 8 in the IUGR group compared with the control group. These urinary markers were not significantly different at week 16 between the two groups. Increased excretion of urinary ß2-MG, Cys-C, and calbindin was observed in IUGR rats at ≥8 weeks of age. CONCLUSION: Children born with IUGR are at increased risk for renal tubular damage.

Impaired nephrogenesis in neonatal rats with oxygen-induced retinopathy.

BACKGROUND: Preterm neonates are born while nephrogenesis is ongoing, and are commonly exposed to factors in a hyperoxic environment that can impair renal development. Oxidative stress has also been implicated in the development of retinopathy of prematurity (ROP). The rat model of oxygen-induced retinopathy (OIR) is the most clinically relevant model of ROP because its biologic features closely resemble those of ROP in preterm infants. We investigated impaired renal development in a rat model of OIR. METHODS: Newborn Sprague-Dawley rats were maintained in either a normoxic (room air, 21% O2 ; control group) or a controlled hyperoxic (80% O2 ; OIR group) environment from birth to postnatal day (P) 12. All pups were then raised in room air from P12 to P19. RESULTS: The hyperoxic environment led to significantly higher urinary excretion of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative DNA damage, and a reduction in nephrogenic zone width at P5 in OIR pups. Additionally, glomerular count was significantly reduced by 20% in the OIR group, and avascular and neovascular changes in the retina were observed only in the OIR group at P19. Messenger RNA levels of vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor-ß, essential angiogenic cytokines for glomerulogenesis, in the renal cortex were significantly lower at P5 and significantly higher at P19 in the OIR group compared with controls. CONCLUSION: Renal impairment was caused by exposure to a hyperoxic environment during nephrogenesis, and the pathology of the impaired nephrogenesis in this OIR model reflects the characteristics of ROP observed in preterm infants.

Effect of insulin-like growth factor-I during the early postnatal period in intrauterine growth-restricted rats.

BACKGROUND: Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period. METHODS: Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed. RESULTS: Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA. CONCLUSIONS: No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period.

Evaluation of kidney dysfunction and angiotensinogen as an early novel biomarker of intrauterine growth restricted offspring rats.

BACKGROUND: Few studies have addressed the growing concerns of chronic kidney diseases in children with intrauterine growth restriction (IUGR). Therefore, the purpose of this study was to evaluate long-term kidney dysfunction and determine if urinary angiotensinogen (AGT) was suitable as a novel early biomarker for kidney dysfunction in IUGR offspring. METHODS: Pregnant rats underwent bilateral uterine artery ligation, and as a control group, sham surgeries were performed. RESULTS: The birth weight was reduced, the urinary AGT to creatinine ratio was significantly higher at week 20, and urinary protein levels were significantly higher at week 32 in IUGR rats than in control rats. On the other hand, the histological findings at week 32 revealed long-term kidney dysfunction, more severe glomerulosclerosis, and greater glomerular diameters in IUGR rats. Moreover, AGT mRNA expression and immunohistological staining were significantly increased in IUGR rats; this suggests that the intrarenal renin-angiotensin system (RAS) contributes to renal dysfunction of IUGR offspring. CONCLUSION: Urinary AGT elevation prior to urinary protein levels suggests that AGT is an early biomarker. At week 32, kidney dysfunction was severe in IUGR rats and intrarenal RAS appeared to be one of the causes.