Constructive rescue of TFIIH instability by an alternative isoform of XPD derived from a mutated XPD allele in mild but not severe XP-D/CS.

Mutations in XPD cause xeroderma pigmentosum (XP), XP and Cockayne syndrome (CS) crossover syndrome (XP/CS), trichothiodystrophy and cerebro-oculo-facio-skeletal syndrome (COFS). COFS represents the most severe end of the CS spectrum. This study reports two Japanese patients, COFS-05-135 and COFS-Chiba1, who died at ages of <1 year and exhibited typical COFS manifestations caused by XPD mutations p.[I619del];[R666W] and p.[G47R];[I619del], respectively. Two other cases of severe XP-D/CS (XP group D/CS), XP1JI (p.[G47R];[0]) and XPCS1PV (p.[R666W];[0]), died at ages <2 years. On the other hand, two cases of mild XP-D/CS, XP1NE (p.[G47R];[L461V;V716_R730del]) and XPCS118LV (p.[L461V;V716_R730del];[R666W]), lived beyond 37 years of age. p.I619Del and p.[L461V;V716_R730del] are functionally null; therefore, despite the differences in clinical manifestations, the functional protein in all of these patients was either p.G47R or p.R666W. To resolve the discrepancies in these XPD genotype-phenotype relationships, the p.[L461V;V716_R730del] allele was analyzed and we found that p.[L461V;A717G] was expressed from the same allele as p.[L461V;V716_R730del] by authentic splicing. Additionally, p.[L461V;A717G] could partially rescue the loss of XPD function, resulting in the milder manifestations observed in XP1NE and XPCS118LV.

Cord serum adiponectin is positively related to postnatal body mass index gain.

BACKGROUND: The roles of adiponectin and leptin in the early stages of life are poorly understood. We previously studied longitudinal changes in these adipocytokines from birth to 12 months of age. The aim of this investigation was to evaluate the correlation between cord serum adipocytokine levels and postnatal growth by 3 years of age. METHODS: A questionnaire was sent to obtain the general physical measurements of 3-year-olds from 56 healthy newborn infants born at a gestational age of 35 weeks or more; 45 valid responses were obtained. The correlations between variables, including cord serum adipocytokine levels at birth and general physical measurements at 3 years, were investigated. RESULTS: Body mass index (BMI) Z-score gain from birth to 3 years was negatively correlated with birthweight SD scores (ß=-0.395, P= 0.019) and gestational age (ß=-0.557, P= 0.016), and positively correlated with cord serum adiponectin levels (ß= 0.253, P= 0.043). BMI Z-score gain from birth to 6 months was negatively correlated with only birthweight SD score (ß=-0.442, P= 0.017). Cord serum leptin levels were not a significant predictor of BMI Z-scores gain in our subjects. BMI Z-scores at 6 months, 12 months, and 3 years of age were not related to cord serum adiponectin or leptin levels. CONCLUSIONS: Birthweight SD score, gestational age, and cord serum adiponectin levels are significant predictors of BMI Z-score gain from birth to 3 years of age in Japanese infants.

Low HCMV DNA copies can establish infection and result in significant symptoms in extremely preterm infants: a prospective study.

Breast milk (BM) is the main source of human cytomegalovirus (HCMV) infection. We examined whether the number of HCMV DNA copies in BM is related to HCMV infection in very low birth weight (VLBW) infants. We identified 11 pairs of VLBW infants and mothers. BM samples were collected every week until 10 weeks postpartum. Urine samples were collected from the infants within 1 week, at 6 to 8 weeks, at discharge, and whenever HCMV infection was suspected. HCMV DNA in BM was positive in 7 of 11 mothers and reached a peak at 4 to 5 weeks postpartum. Of the 11, 5 infants were determined to be infected from positive HCMV DNA in the urine, despite the fact that BM was used after being frozen. Of the five, four infected infants exhibited symptoms between 35 and 60 days of age. Symptomatic infants had longer stays and slower weight gain. The HCMV infection rate is high in very preterm infants. A new strategy to prevent HCMV infection other than freezing should therefore be established.

Neonatal sucking behavior: comparison of perioral movement during breast-feeding and bottle feeding.

BACKGROUND: The aim of the present study was to compare orofacial motion and mouth angle during breast-feeding and bottle feeding in normal infants. METHODS: Thirteen normal infants were enrolled in the study, and feeding sessions were recorded using a digital video camera at 4 or 5 days following birth. The analysis was successfully performed for 12 infants during both breast-feeding and bottle feeding. Markers were placed at the lateral angle of the eye, the tip of the jaw, and the throat region. Jaw and throat region movements were calculated using the direct linear transformation method. The angle of the mouth was also measured. RESULTS: Throat region movement was significantly larger than jaw movement in both breast-feeding (eye-throat region changes: 1.51 +/- 0.37 mm, eye-jaw changes: 0.91 +/- 0.31 mm, P < 0.001) and bottle feeding (eye-throat region changes: 2.91 +/- 0.46 mm, eye-jaw changes: 1.77 +/- 0.33 mm, P < 0.001). Jaw and throat region movements were significantly smaller during breast-feeding than those during bottle feeding (P < 0.001). The angle of the mouth during breast-feeding is larger than that during bottle feeding (P < 0.001). There was a negative correlation between the angle of the mouth and jaw movement. CONCLUSIONS: Jaw and throat region movements during bottle feeding differ from those during breast-feeding. This partly results from the difference in the angle of the mouth during feeding.

Accumulation of subcutaneous fat, but not visceral fat, is a predictor of adiponectin levels in preterm infants at term-equivalent age.

BACKGROUND: Preterm infants have altered fat tissue development, including a higher percentage of fat mass and increased volume of visceral fat. They also have altered adiponectin levels, including a lower ratio of high-molecular-weight adiponectin (HMW-Ad) to total adiponectin (T-Ad) at term-equivalent age, compared with term infants. AIMS: The objective of this study was to investigate the association between adiponectin levels and fat tissue accumulation or distribution in preterm infants at term-equivalent age. STUDY DESIGN: Cross-sectional clinical study. SUBJECTS: Study subjects were 53 preterm infants born at ≤34weeks gestation with a mean birth weight of 1592g. OUTCOME MEASURES: Serum levels of T-Ad and HMW-Ad were measured and a computed tomography (CT) scan was performed at the level of the umbilicus at term-equivalent age to analyze how fat tissue accumulation or distribution was correlated with adiponectin levels. RESULTS: T-Ad (r=0.315, p=0.022) and HMW-Ad levels (r=0.338, p=0.013) were positively associated with subcutaneous fat area evaluated by performing CT scan at term-equivalent age, but were not associated with visceral fat area in simple regression analyses. In addition, T-Ad (ß=0.487, p=0.003) and HMW-Ad levels (ß=0.602, p<0.001) were positively associated with subcutaneous fat tissue area, but they were not associated with visceral fat area also in multiple regression analyses. CONCLUSION: Subcutaneous fat accumulation contributes to increased levels of T-Ad and HMW-Ad, while visceral fat accumulation does not influence adiponectin levels in preterm infants at term-equivalent age.

Predictors of low milk volume among mothers who delivered preterm.

BACKGROUND: Factors associated with successful provision of mother's own milk (MOM) for premature infants in a Japanese neonatal intensive care unit (NICU) context are not well known. OBJECTIVE: We determined the independent risk factors for low milk volume at day 4 postpartum and formula feeding at the time of NICU discharge. METHODS: We reviewed the medical records of mothers who delivered at < 32 weeks' gestation. We determined maternal, premature infant, and milk expression variables predictive of (1) day 4 postpartum milk volume being less than the cohort median and (2) formula feeding at the time of NICU discharge, reported as adjusted odds ratios (95% confidence interval). RESULTS: Among 85 dyads, median (quartile range) milk volume on day 4 postpartum was 153 (34-255) mL. The rate of formula feeding at discharge was 42%. Mothers delivering by cesarean (vs vaginal) delivery had 4.3-fold (1.5-12.4) greater odds of day 4 milk volume < median (P < .01). Pregnancy-induced hypertension, delayed milk expression initiation, and low pumping frequency were strongly associated with cesarean delivery. Subsequently, mothers with day 4 milk volume < median (vs ≥ median) had 7.1-fold (2.6-19.5) greater odds of formula feeding at discharge (P < .01). CONCLUSION: Cesarean delivery is associated with lower milk volume on day 4 but may represent a composite of underlying risk factors for low milk volume in the early postpartum period. Further, low milk volume on day 4 is a strong correlate of lack of exclusive breast milk feeding at NICU discharge.

A neonate with an anomalous bone attached to the cervical spine.

BACKGROUND CONTEXT: A digit/rib-like ectopic bone is a rare congenital anomaly that is most commonly seen in the thorax or pelvis. There is a single report of an adult possessing a phalanx-like bone in the cervical region; however, whether the abnormal bone was congenital or acquired remains elusive. PURPOSE: To elucidate that a phalanx-like bone in the cervical region represents a congenital anomaly. STUDY DESIGN: Case report. METHODS: Report of the imaging findings in a neonate with a palpable bone projection in the posterior neck. RESULTS: Plain radiographs demonstrated an ectopic bone posterior to the spinous process of the C5 vertebra. Three-dimensional computed tomography demonstrated that the anomalous bone was attached to the left lamina of the C5 vertebra and that there was abnormal segmentation of the left side of the cervical spine. CONCLUSIONS: The anomalous bone in the neck is a congenital malformation that is accompanied by the maldevelopment of the cervical spine.

Preterm infants have altered adiponectin levels at term-equivalent age even if they do not present with extrauterine growth restriction.

BACKGROUND/AIMS: This study aimed to investigate total adiponectin (T-Ad) and high-molecular-weight adiponectin (HMW-Ad) levels in preterm infants at term-equivalent age and to assess the relationship between adiponectin levels and early postnatal growth. METHODS: The study included 43 term infants and 58 preterm infants born at 34 weeks' gestation or less. T-Ad and HMW-Ad levels were measured in the preterm infants at birth and at term-equivalent age, and in the term infants at birth. Adiponectin levels were statistically compared between preterm and term infants to evaluate the association between postnatal growth and changes in the adiponectin levels in preterm infants. RESULTS: The T-Ad levels were higher and the ratio of HMW-Ad to T-Ad (HMW%) was lower in preterm infants at term-equivalent age than in term infants. Further, body weight SD score changes were positively associated with T-Ad and HMW-Ad increases in preterm infants from birth to term-equivalent age. The HMW% changes had a negative association only with HMW% in cord blood. CONCLUSION: Preterm infants have altered adiponectin levels at term-equivalent age. Further, postnatal growth may contribute to adiponectin increases from birth to term-equivalent age, although HMW% changes might be regulated before birth at least up to term-equivalent age in preterm infants.

Altered metabolisms of mediators controlling vascular function and enhanced oxidative stress in asymptomatic children with congenital portosystemic venous shunt.

Children with congenital portosystemic venous shunt (PSVS) are at risk for developing pulmonary hypertension, irrespective of the severity of portal hypertension or liver damage. Altered metabolisms of nitric oxide (NO) and endothelin-1 (ET-1), which are linked with oxidative stress and control vascular tone, might contribute to the vascular disturbance. This study examined 14 children (aged 1-5 years) with congenital PSVS lacking major liver damage and portal hypertension. Serum levels of nitrite/nitrate (NOx) as stable metabolites of NO, and of asymmetric dimethylarginine (ADMA) as an endogenous NO synthase inhibitor were determined, along with the plasma level of ET-1. Oxidative stress, which might affect the production of such mediators, was also examined using specific urinary and blood markers. The NOx levels were significantly lower in affected children than in the age-matched control group, although ET-1 levels were significantly higher than the control levels. In the affected children, the ADMA levels and ADMA/NOx ratios were higher, respectively, by 30% and 130% and showed significant positive correlations with the shunt ratios. Oxidative stress markers, including plasma thiobarbiturate reactive substances and urinary acrolein-lysine and 8-hydroxy-2'-deoxyguanosine, were significantly higher in affected children than in the control group, consistent with them being subjected to enhanced oxidative stress. These results suggest the presence of altered metabolisms of vascular mediators and enhanced oxidative stress in asymptomatic preschool children with congenital PSVS.

Completely separated scrotum and vesicointestinal fistula without exstrophy as a novel manifestation of aphallia: a case report.

A male infant born at 32 weeks of gestation and weighing 1.44 kg had penile agenesis, bifid scrotums, an anorectal anomaly, and suspected omphalocele. An operation revealed complete urethral agenesis, duplicated and blind bowels, a vesicointestinal fistula without exstrophy, and a urachal fistula; however, no omphaloceles were detected. To our knowledge, this is the first report on aphallia accompanied with completely separated scrotum and a vesicointestinal fistula without exstrophy; this condition is associated with urorectal septum malformation sequence (URSMS) and covered cloacal exstrophy. The possible embryogenesis is discussed in this study.