Kayo Yoshikawa

Gray matter volumetric MRI differences late-preterm and term infants

Gray matter develops rapidly during the third trimester of pregnancy, which is a critical period for lipid deposition. We measured brain volume in term and late-preterm infants to determine if it is related to disabilities in late-preterm infants. In addition, we measured serum lipid concentrations to investigate the relationship between brain volume and lipid nutrition. Magnetic resonance imaging scans were obtained in 16 late-preterm and 13 term infants. We measured cerebrum, gray matter, and white matter volumes. We performed serum cholesterol, triglyceride (TG), and lipoprotein analyses in cord blood by high-performance liquid chromatography using gel permeation columns to assess lipid nutritional levels. The gray matter volume and percent cerebrum volume of gray matter were significantly smaller in late-preterm infants (p<0.001). Head circumference and cerebrum and white matter volume did not differ between the two groups. Gray matter volume correlated positively with gestational age (r=0.647, p<0.001), head circumference (r=0.688, p<0.001), and high-density lipoprotein (HDL)-TG levels (r=0.496, p=0.006). Late-preterm infants had a normal head circumference and a lower gray matter volume than term infants. Gestational age and head circumference were significantly associated with gray matter volume. Only HDL-TG levels were significantly associated with gray matter volume. HDL-TG might contribute to the transport of fatty acids and gray matter development during the postnatal period. Thus, delayed gray matter development may partly contribute to neurodevelopmental disabilities in late-preterm infants.

Early postnatal alteration of body composition in preterm and small-for-gestational-age infants: implications of catch-up fat

The concept of the developmental origins of health and disease is based on studies by Barker et al. They proposed a hypothesis that undernutrition in utero permanently changes the body’s structure, function, and metabolism in ways that lead to atherosclerosis and insulin resistance in later life. In addition, profound effects on the extent of body fatness and insulin sensitivity are demonstrated, if there is a “mismatch” between prenatal and postnatal environments. In previous studies, undernutrition in utero has been evaluated simply by birth weight itself or birth weight for gestational age, and the degree of mismatch has been estimated by postnatal rapid weight gain. Recently, we investigated subcutaneous fat accumulation in small-for-gestational-age infants and found that a rapid catch-up in skinfold thickness developed prior to the body weight catch-up. Furthermore, insulin-like growth factor-I and lipoprotein lipase mass concentrations also demonstrate rapid increase during the neonatal period with fat accumulation. Investigating the precise mechanisms of developmental origins of health and disease including mediating metabolic and hormonal factors may provide a new approach to prevent atherosclerosis and insulin resistance. Better management of undernutrition during gestation and neonatal growth during the early postnatal period is an important theme for future health.

Residual blood volume in the umbilical cord of extremely premature infants.

The aim of this study was to investigate residual blood volume in the umbilical cord of extremely premature infants.

Association between serum lipoprotein lipase mass concentration and subcutaneous fat accumulation during neonatal period.

Background/Objectives:Subcutaneous adipose tissue grows rapidly during the first months of life. Lipoprotein lipase (LPL) has a quantitatively important function in adipose tissue fat accumulation and insulin-like growth factor-I (IGF-I) is a determinant of neonatal growth. Recent studies showed that LPL mass in non-heparinized serum (LPLm) was an index of LPL-mediated lipolysis of plasma triacylglycerol (TG). The objective was to know the influence of serum LPL and IGF-I on neonatal subcutaneous fat growth, especially on catch-up growth in low birth weight infants.Subjects/Methods:We included 47 healthy neonates (30 males, 17 females), including 7 small for gestational age. We measured serum LPLm and IGF-I concentrations at birth and 1 month, and analyzed those associations with subcutaneous fat accumulation.Results:Serum LPLm and IGF-I concentrations increased markedly during the first month, and positively correlated with the sum of skinfold thicknesses both at birth (r=0.573, P=0.0001; r=0.457, P=0.0035) and at 1 month (r=0.614, P<0.0001; r=0.787, P<0.0001, respectively). In addition, serum LPLm concentrations correlated inversely to very low-density lipoprotein (VLDL)-TG levels (r=−0.692, P<0.0001 at birth; r=−0.429, P=0.0052 at 1 month). Moreover, the birth weight Z-score had an inverse association with the postnatal changes in individual serum LPLm concentrations (r=−0.639, P<0.0001).Conclusions:Both serum LPLm and IGF-I concentrations were the determinants of subcutaneous fat accumulation during the fetal and neonatal periods. During this time, LPL-mediated lipolysis of VLDL-TG may be one of the major mechanisms of rapid growth in subcutaneous fat tissue. Moreover, LPL, as well as IGF-I, may contribute to catch-up growth in smaller neonates.

Early postnatal changes of lipoprotein subclass profile in late preterm infants

BACKGROUND Late preterm infants (LPIs; 34-37 gestational weeks at birth) have higher risk for several morbidities than do term infants (TIs). It has been suggested that a cholesterol and fatty acid supply may improve their outcomes. We investigated the lipoprotein subclass profile in LPIs to evaluate their early postnatal lipid metabolism. METHODS Eighty-one infants (25 LPIs, 56 TIs) were included. Cholesterol and triglyceride (TG) concentrations in 12 lipoprotein subclasses were measured at birth and at 1 month using HPLC. RESULTS In LPIs, the cord blood exhibited higher cholesterol concentrations in medium and large subclasses of very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) compared to the values in TIs. During the first month of life, LPIs had greater increases in cholesterol concentrations of medium and large subclasses of VLDL than TIs, whereas postnatal increases in cholesterol concentrations of medium and large subclasses of LDL and HDL were smaller. TG concentrations were not different in each VLDL subclass at birth and at 1 month. CONCLUSIONS In LPIs, cord blood lipoprotein subclass profiles and the early postnatal change exhibited different, especially in cholesterol concentrations.

Treatment responses for disseminated intravascular coagulation in 25 children treated with recombinant thrombomodulin: A single institution experience

INTRODUCTION Recombinant thrombomodulin (rTM), which degrades factors Va and VIIIa by activating protein C, has been developed as a new drug for treating disseminated intravascular coagulation (DIC). MATERIALS AND METHODS Since July 2009, we have treated 25 children with DIC using rTM (380 U/kg/day, or 130 U/kg/day for newborns) as a first-line therapy. Median duration of rTM administration was 5 consecutive days (range, 2-13 days). We employed DIC criteria of the Japan Welfare and Health Ministry. The first day on which rTM treatment was given was defined as day 1. RESULTS Median patients age was 3 years. Underlying diseases were hematological disorders (n=13) and severe infection (n=12). Overall, 20 of the 25 patients had recovered from DIC by day 7 and 22 of the 25 patients remained alive at day 28. Median Pediatric Logistic Organ Dysfunction score improved from 11 on day 1 to 2 on day 7 (p=0.009). Laboratory data (median) on day 7 (prothrombin time (PT) ratio, 1.15; fibrin and fibrinogen degradation products (FDP), 9.6 mg/l; D-dimer, 1.6 mg/l FEU; antithrombin, 112%; protein C, 105%) were significantly improved compared to results on day 1 (PT ratio, 1.39; FDP, 21.6 mg/l; D-dimer, 6.4 mg/l FEU; antithrombin, 86%; protein C, 54%). Whereas, 5 patients failed to respond and serious bleeding events were observed in 2 newborns. CONCLUSION The efficacy of rTM cannot be assessed from the present dataset, due to several limitations such as the small heterogenous patient cohort, and the lack of age- and disease-matched controls. Nevertheless, this case-series remains important in terms of enabling further prospective control studies to evaluate the efficacy of rTM in children.

Insulin-like growth factor-1 and lipoprotein profile in cord blood of preterm small for gestational age infants

Low birth weight was associated with cardiometabolic diseases in adult age. Insulin-like growth factor-1 (IGF-1) has a crucial role in fetal growth and also associates with cardiometabolic risks in adults. Therefore, we elucidated the association between IGF-1 level and serum lipids in cord blood of preterm infants. The subjects were 41 consecutive, healthy preterm neonates (27 male, 14 female) born at <37-week gestational age, including 10 small for gestational age (SGA) infants (<10th percentile). IGF-1 levels and serum lipids were measured in cord blood, and high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC) and very low-density lipoprotein triglyceride (VLDLTG) levels were determined by HPLC method. SGA infants had lower IGF-1 (13.1 ± 5.3 ng/ml), total cholesterol (TC) (55.0 ± 14.8), LDLC (21.6 ± 8.3) and HDLC (26.3 ± 11.3) levels, and higher VLDLTG levels (19.0 ± 12.7 mg/dl) than in appropriate for gestational age (AGA) infants (53.6 ± 25.6, 83.4 ± 18.9, 36.6 ± 11.1, 38.5 ± 11.6, 8.1 ± 7.0, respectively). In simple regression analyses, log IGF-1 correlated positively with birth weight (r = 0.721, P < 0.001), TC (r = 0.636, P < 0.001), LDLC (r = 0.453, P = 0.006), and HDLC levels (r = 0.648, P < 0.001), and negatively with log TG (r = -0.484, P = 0.002) and log VLDL-TG (r = -0.393, P = 0.018). Multiple regression analyses demonstrated that IGF-1 was an independent predictor of TC, HDLC and TG levels after the gestational age and birth weight were taken into account. In preterm SGA infants, cord blood lipids profile altered with the concomitant decrease in IGF-1 level.

Hemolytic disease of the newborn due to anti-E and anti-c antibody following maternal transfusion

The major cause of hemolytic disease of the newborn (HDN) due to blood type incompatibility is ABO incompatibility, while HDN due to other alloantibodies (anti-C, anti-c, anti-E, anti-e, and anti-kell) is rare. We describe here an infant diagnosed with HDN due to anti-E antibody (Ab) and anti-c Ab incompatibility following maternal red blood cell (RBC) transfusion received at the previous delivery for post-partum hemorrhage. We examined the blood products transfused to the mother, and the infant’s blood, and we detected alloantibodies in the previously transfused blood products.

The target value of oxygen saturation during the first 10 minutes after birth

During neonatal resuscitation, careful oxygenation is needed. Pulse oximetry is recommended to evaluate the need for oxygenation, but it is not clear whether peripheral perfusion is adequate for the evaluation of arterial oxygen saturation (SpO2). Additionally, there has been no study on the changes in SpO2 immediately after birth in Japan, despite the indispensable need for definitive oxygenation criteria.

Congenital adrenal hyperplasia and violation of newborn screening procedures

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. CAH can cause a life-threatening adrenal crisis. In most developed countries, including Japan, neonatal screening for 21-hydroxylase deficiency is an approved part of the newborn screening program. The blood sample used for screening tests for 17-hydroxyprogesterone (17-OHP) is obtained via heel puncture and collected using filter paper within 7 days of birth. Screening markedly decreases the time to diagnosis for infants with CAH. Morbidity and mortality are also reduced due to early diagnosis and the prevention of severe salt wasting (SW). After blood sample collection, the filter paper is dehydrated, and the medical institution immediately sends it individually to the testing institution by mail. In 1989, a newborn screening program for CAH was implemented in Japan, and it has been effective in preventing infant adrenal crises. Here, we report the case of a 13-day-old newborn who developed adrenal crisis due to delay in submitting the filter paper to the testing institution.