[A clinical analysis of hypothyroidism in very low birth weight/extremely low birth weight infants].

OBJECTIVE: To study the risk factors and treatment outcome of hypothyroidism in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The VLBW/ELBW infants who were diagnosed with hypothyroidism from September 2018 to December 2019 were enrolled as the case group (n=29). The children with normal thyroid function, matched at a ratio of 1 : 3, were enrolled as the control group (n=87). Clinical features were compared between the two groups. The correlation of thyroid function with gestational age and birth weight and the risk factors for hypothyroidism were analyzed. RESULTS: A total of 162 VLBW/ELBW infants who met the inclusion criteria were enrolled, with 29 infants in the case group (an incidence rate of hypothyroidism of 17.9%). The lower the birth weight, the higher the incidence rate of hypothyroidism (P<0.05). Triiodothyronine (T3) and free T3 were positively correlated with gestational age (P<0.05). T3 and free thyroxine were positively correlated with birth weight (P<0.05). Small for gestational age, multiple birth, maternal age ≥ 35 years, and use of dopamine were independent risk factors for hypothyroidism (P<0.05). In the case group, 16 infants were treated with levothyroxine (5-10 µg/kg daily), and the thyroid function returned to normal after 2 weeks of treatment. CONCLUSIONS: There is a high incidence rate of hypothyroidism in VLBW/ELBW infants. Small for gestational age, multiple birth, advanced maternal age, and use of dopamine are risk factors for hypothyroidism. The infants treated with levothyroxine should be followed up regularly to ensure an appropriate dose.

[Clinical effect of letrozole in treatment of idiopathic short stature in adolescent boys].

OBJECTIVE: To evaluate the therapeutic effect and safety of letrozole in the treatment of adolescent boys with idiopathic short stature (ISS). METHODS: A retrospective analysis was performed for the clinical data of 16 adolescent boys with ISS who had a bone age of ≥14 years. Among these boys, 8 were initially treated with recombinant human growth hormone (rhGH), followed by rhGH combined with letrozole during a bone age of 14-15.5 years. The other 8 boys were initially treated with rhGH combined with letrozole since their bone age was ≥14 years at diagnosis. Of the 16 boys, 16 were treated for not less than 6 months, 12 were treated for not less than 1 year, and 5 were treated for not less than 1.5 years. The increase in bone age, predicted adult height (PAH), final adult height, sex hormones, and adverse reactions after treatment were analyzed. RESULTS: After 6 months, 1 year, and 1.5 years of treatment, median bone age was increased by 0 year, 0.5 year, and 0.5 year respectively, which was significantly lower than the increase in age (P<0.05). There was a significant increase in PAH after treatment (P<0.05). Seven boys reached final height, which was significantly higher than PAH before treatment (P<0.05). All the 16 boys had significant increases in luteinizing hormone, follicle-stimulating hormone, and testosterone levels after treatment (P<0.05), with a significant reduction in the estradiol level and a significant increase in the insulin level at 1 year of treatment (P<0.05). There was a significant increase in the insulin-like growth factor-1 level at 6 months and 1 year of treatment (P<0.05). There were no significant changes in blood glucose, blood lipids, uric acid, and the three indices for thyroid function as monitored during treatment (P>0.05). CONCLUSIONS: In adolescent boys with ISS and a high bone age, rhGH combined with letrozole can safely and effectively delay the increase in bone age and improve PAH and final adult height, with little adverse effect.

[17α-Hydroxylase deficiency with severe hypertension as the initial symptom in a child].

A 14-year-old female (social gender) patient was admitted to the hospital due to severe hypertension for 11 days. The patient had primary amenorrhea. The blood pressure was 146/90 mm Hg. The skin color was slightly black. The development of secondary sexual characteristics was poor. The labia majora could be observed in the vulva. However, the labia minora, clitoris, vagina, and hymen were absent. The levels of renin, cortisol, and sex hormone were low, while the levels of adrenocorticotropic hormone and gonadotropin were high. The levels of blood potassium and aldosterone were both normal. Radiography indicated retardation of bone age. Ultrasound examination revealed that the ovary and uterus were both absent. The patient had bilateral adrenal hyperplasia and cryptorchid testes located in both inguinal canals. The patient had a 46,XY karyotype. Whole genome sequencing revealed two homozygous mutations, c.985T>C and c.987delC, in exon 6 of the CYP17A1 gene of the patient and heterozygous mutations in the same sites of the parents. The patient was diagnosed with congenital adrenal hyperplasia-17α-hydroxylase deficiency. After treatment with hydrocortisone for 2 months, blood pressure returned to normal and the level of adrenocorticotropic hormone was reduced. According to the request of the patient and the parents, hydrocortisone was replaced with estrogen to allow the patient to live as a female. The patient also received surgical excision of cryptorchid testes to prevent gonadal malignancy. It is concluded that in the differential diagnosis of pediatric hypertension, sexual development should be considered and the levels of adrenocorticotropic hormone and cortisol should be evaluated. The rare disease 17α-hydroxylase deficiency should be considered for patients with low-renin hypertension and gonadal dysgenesis.

[A survey of pubertal development in children born with assisted reproductive technology].

OBJECTIVE: To investigate the status of pubertal development in children born with assisted reproductive technology (ART). METHODS: A retrospective analysis was performed on the pubertal development data of children born with ART in Peking University Third Hospital from 1994 to 2003 (ART group). The data in the cross-sectional study "Reports on the Physical Fitness and Health Research of Chinese School Students in 2010" were used as a control. The age at menarche and the age at spermarche were compared between the two groups. The status of pubertal development in the overweight and obese children in the ART group was evaluated to investigate the correlation between pubertal development and body mass index (BMI). RESULTS: A total of 200 children born with ART were enrolled in this study, and 72 of them (41 males and 31 females) completed the survey (response rate=36.0%). In the ART group, the mean age at spermarche and the mean age at menarche were 13.9 years (95%CI: 13.7-14.3 years) and 12.2 years (95%CI: 11.8-12.6 years), respectively. There were no significant differences in the age at spermarche and the age at menarche between the ART and control groups (P>0.05). In the ART group, there were no significant differences in the age at spermarche and the age at menarche between the overweight and obese children and the normal weight children (P>0.05). There were also no significant differences in overweight rate and obesity rate between the children in the ART group and the adolescents in Beijing (P>0.05). In the ART group, there was no significant correlation between the age at spermarche or menarche and BMI (P>0.05). CONCLUSIONS: No delayed or precocious puberty is observed in children born with ART. This is consistent with the normal control data. And there is no significant correlation between pubertal development and BMI in children born with ART.

[Characteristics of R bone age, C bone age, and T bone age in children with different causes of short stature based on Tanner and Whitehouse skeletal age assessment system 2].

OBJECTIVE: To study the characteristics of R bone age, C bone age, and T bone age in children with different causes of short stature based on the Tanner and Whitehouse skeletal age assessment system 2 (TW2), and to provide a reference for the etiological diagnosis of short stature. METHODS: Three hundred and sixty-three children with previously untreated short stature were classified into four groups according to the causes: growth hormone deficiency (GHD; 27 cases), idiopathic short stature (ISS; 280 cases), small for gestational age (SGA; 41 cases), and Turner syndrome (TS; 15 cases). The X-ray films of their left hand-wrist bones were taken to determine the bone age. R bone age, C bone age, and T bone age were assessed by the TW2 method and compared with their chronological age (CA). RESULTS: R bone age, C bone age, and T bone age were over 2 years less than CA in both boys and girls from the GHD group. In the ISS group, R bone age, C bone age, and T bone age were about 1 year less than CA in boys, while there were no significant differences between the bone ages and CA in girls. In the SGA group, there were no significant differences between the bone ages and CA in either boys or girls. In the TS group, R bone age and T bone age were significantly lower than CA, while there was no significant difference between C bone age and CA. CONCLUSIONS: The children with different causes of short stature have different characteristics of R bone age, C bone age, and T bone age assessed by the TW2 method. The assessment of R bone age, C bone age, and T bone age by the TW2 method is helpful for the etiological diagnosis of short stature in children.

[Clinical features of respiratory diseases in late preterm neonates].

OBJECTIVE: To evaluate the clinical features of respiratory diseases of late preterm neonates. METHODS: Six hundred and thirty late preterm infant(gestational age: 34~36+6weeks),4401 cases of term infants and 328 early preterm infants who were born at the obstetrical department of Peking University 3rd Hospital from January 2009 to December 2010 were enrolled. Among them 84 late preterm infants, 135 term infants and 182 early preterm infants developed respiratory diseases. The incidence of respiratory diseases,clinical features and the severity of the diseases were compared among the three groups. RESULTS: The incidence and mortality rates of respiratory diseases and the percentage of severe cases were significantly higher in the late preterm group than in the term group, but lower than in the early preterm group (P<0.01). The symptoms of respiratory disease occurred earlier in the late preterm group than in the term group, but later than in the early preterm group (P<0.01). The late preterm group had a significantly higher incidence of tachypnea and lower incidence of retraction sign when compared with the term and early preterm groups (P<0.05). The percentages requiring oxygen therapy and mechanical ventilation in the late preterm group were both significantly higher than in the term group, but lower than in the early preterm group (P<0.05). The multiple linear regression analysis showed 11 factors associated with the severity of respiratory diseases: decreased arterial partial pressure of oxygen, hematokrit, pH value and respiratory rate, arterial oxyhemoglobin saturation, systolic arterial pressure, 5 minute Apgar score and gestational age, and increased blood urea nitrogen, heart rate and respiratory rate. CONCLUSIONS: Late preterm infants are more likely to develop respiratory diseases than term infants, and to develop a more severe condition and need a more intensive respiratory support treatment. Tachypnea is a common presentation of dyspnea in late preterm infants and occurs earlier than in term infants but later than in early preterm infants. It may usually indicate a serious condition when dyspnea, abnormal heart rate and blood pressure, and multisystem damages occur in late preterm infants.

[Cockayne syndrome].

Cockayne syndrome is a rare autosomal recessive disease. This paper reports a case of Cockayne syndrome confirmed by gene analysis. The baby (male, 7 years old) was referred to Peking University Third Hospital with recurrent desquamation, pigmentation and growth and development failure for 6 years, and recurrent dental caries and tooth loss for 2 years. Physical examination showed very low body weight, body length and head circumference, yellow hair, a lot of fawn spots on the face, skin dry and less elastic, and subcutaneous lipopenia. He had an unusual appearance with sunken eyes, sharp nose, sharp mandible, big auricle and dental caries and tooth loss. Crura spasticity and ataxia with excessive tendon reflexion, and ankle movement limitation while bending back were observed. He had slured speech. The level of serum insulin like growth factor I was low, and the results of blood and urinary amino acid analysis suggested malnutrition. The results of blood growth hormone, thyroxin, parathyroxin, liver function, renal function, lipoprotein profile and blood glucose and electrolytes were all within normal limit. An electronic hearing examination showed moderate neural hearing loss. The sonogram of eyes revealed small eye axis and vitreous body opacity of right side. MRI of brain revealed bilateral calcification of basal ganglia and generalized cerebral and cerebellar atrophy, and brainstem and callus were also atrophic. Genetic analysis confirmed with CSA gene mutation. So the boy was definitely diagnosed with Cockayne syndrome. He was discharged because of no effective treatment.

[Relationship between ACE gene insertion or deletion polymorphism and left ventricular mass in newborns admitted to the neonatal intensive care unit].

OBJECTIVE: To study the relationship between angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and left ventricular mass (LVM) in newborns admitted to the neonatal intensive care unit (NICU). METHODS: Seventy-two newborns admitted to the NICU were enrolled. ACE genotypes were determined by genomic DNA which was isolated from heel-prick blood. Disease status of the newborns was evaluated by the Neonatal Critical Score (draft) on postnatal day 1. LVM and LVM index (LVMI) were evaluated by echocardiography on postnatal days 1-3. RESULTS: DD genotype was identified in 11 cases, ID genotype in 31 cases, and II genotype in 30 cases. There were no significant differences in clinical characteristics, critical score and body measurements in newborns with different genotypes. The DD genotype group showed significantly lower LVMI than the group with ID+II genotypes (29±4 g/m2 vs 35±8 g/m2; P<0.05). CONCLUSIONS: ACE gene polymorphism is associated with the LVMI in newborns admitted to the NICU. The LVMI of DD genotype carriers is significantly lower than that of ID+II genotypes carriers, which suggests that D allele may be associated with the growth and development of left ventricular.

Two Novel Heterozygous Mutations in ERCC8 Cause Cockayne Syndrome in a Chinese Patient.

BACKGROUND: Cockayne syndrome (MIM #133540, Cockayne syndrome B; 216400, Cockayne syndrome A) is a rare autosomal recessive inherited disease in which the characteristic symptoms are premature aging, cachectic dwarfism, lack of subcutaneous fat, neurological alterations, light sensitivity, and failure to thrive. The mutated gene responsible for this syndrome has been identified as usually either CSA (CKN1, ERCC8) or CSB (ERCC6). In this study, we describe the case of a 7-year-old Chinese boy with characteristic symptoms of Cockayne syndrome A and the conduction of mutation screening of the CSA gene. METHODS: The patient was diagnosed with Cockayne syndrome in the pediatrics clinic for growth failure and developmental delay. We collected peripheral blood samples of the patient and his parents and then extracted the genomic DNA. DNA samples from control subjects and the patient were subjected to polymerase chain reaction amplification. All exons and the flanking intron-exon boundaries of CSA were amplified; then, the polymerase chain reaction products were directly sequenced for mutation screening. RESULTS: Two novel heterozygous CSA mutations, c.551-2A>C and c.394_398delTTACA, were identified in the patient. The c.551-2A>C mutation originates from his father and changed the splice acceptor site AG to CG, thus possibly causing alternative splicing. The c.394_398delTTACA from his mother caused a frameshift after the amino acid at position 132, thus introducing a premature stop codon in the gene sequence. CONCLUSIONS: These mutations extend the mutation spectrum of Cockayne syndrome in the context of Chinese race and provide possibilities of prenatal diagnosis for future offsprings in this family.

WITHDRAWN: Two Novel Heterozygous Mutations of CSA Cause Cockayne Syndrome in a Chinese Family.

This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

No Weight Catch-Up Growth of SGA Infants Is Associated with Impaired Insulin Sensitivity during the Early Postnatal Period.

Objective. To investigate the relationship between weight catch-up growth and insulin sensitivity in small for gestational age (SGA) infants. Methods. Forty-four singleton SGA subjects met the inclusion criteria and finished-3-month followup. Body weight, length, fasting glucose, and fasting insulin (FI) levels were measured at 3 days and 3 months. Insulin sensitivity was evaluated by FI and homeostasis model assessment (HOMA). Results. According to the change of weight Z-score, forty-four subjects were divided into two groups: noncatch-up growth (NCUG) and catch-up growth (CUG). By 3 months of age, the body weight, body length and BMI of NCUG group were significantly lower than those of CUG group. The FI and HOMA were significantly higher in NCUG group. The change of weight Z-score during 3 months was inversely related to the HOMA at 3 months. Conclusion. Our data exemplified that no weight catch-up growth during the first 3 months was associated with impaired insulin sensitivity in SGA infants.

[A meta-analysis of nasal intermittent positive pressure ventilation in treatment of respiratory distress syndrome in premature infants].

OBJECTIVE: To assess the efficacy of nasal intermittent positive pressure ventilation (NIPPV) in treatment of respiratory distress syndrome (RDS) in premature infants. METHODS: According to the requirements of Cochrane systematic review, a thorough literature search was performed among PubMed (1977-2008), Embase (1989-2008), OVID, Cochrane (2008), Chinese Digital Hospital Library (www.chkd.cnki.net) and Chinese Biomedical Literature Disk Database (CBMdisc). Quality assessments of clinical trials were carried out. Randomized controlled trials (RCTs) with NIPPV and RDS were enrolled, and Revman 4.2 software was used for meta-analysis. The trials were analyzed using relative risk (RR) for dichotomous data, weighted mean difference (WMD) were used for continuous data, both kind of data were expressed by 95% confidence intervals (95% CI). For homogenous data (P> or =0.10), fixed effects model was calculated, for heterogeneity data (P<0.10), random effects model was calculated. RESULTS: Five RCTs involving 284 premature infants diagnosed as respiratory distress syndrome (RDS) were included. Three studies comparing NIPPV with nasal continuous positive airway pressure (NCPAP) in the postextubation period, the extubation failure rate was 8.34% vs 40.79% in NIPPV group and NCPAP group, the NIPPV group had significantly lower extubation failure rates [RR 0.21 (95% CI: 0.10-0.45; P<0.001)]. Two of the above-mentioned three studies analyzed bronchopulmonary dysplasia (BPD) rates, the incidence of BPD was 39.34% vs 54.39% in NIPPV group and NCPAP group, the NIPPV group had a trend towards lower BPD rates, but this did not reach statistical significance [RR 0.73 (95% CI: 0.49-1.07; P=0.11)]. NIPPV was used as primary mode in two studies, one compared with conventional ventilation (CV), which detected that the NIPPV group had significantly lower BPD rates (10% vs. 33.33%, P=0.04); the other compared with NCPAP, which also showed that NIPPV group had significantly lower BPD rates (2.33% vs. 17.07%, P=0.03). CONCLUSION: The primary mode NIPPV was found to be feasible as a method of ventilation in preterm infants with RDS, and was associated with a decreased incidence of BPD. In the postextubation period, NIPPV is more effective in preventing failure of extubation than NCPAP.

[Influence of angiotensin converting enzyme gene insertion/deletion polymorphism and beta3-adrenergic receptor gene Trp64Arg polymorphism on fetal growth and neonatal insulin sensitivity].

OBJECTIVE: To understand the influence of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and beta3-adrenergic receptor (beta3-AR) gene Trp64Arg polymorphism on fetal growth and neonatal insulin sensitivity. METHODS: Totally 296 newborn infants were selected into our study and divided into 2 groups according to gestational age and birth weight: adequate-for-gestational-age (AGA) group (222 cases) and small-for-gestational-age (SGA) group (74 case). Serum glucose and insulin were examined in the morning of the 3rd day before milk. Insulin sensitivity was evaluated by homeostasis model assessment (HOMA) equation. beta3-AR gene Trp64Arg polymorphism and ACE gene I/D polymorphism (202 cases) were analysed using polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) technique. Gestational age, birth weight, birth weight percentage, serum glucose, insulin and HOMA-IR were compared among different genotype groups. Statistical analysis was performed with the SPSS 10.0 software. RESULTS: No significant difference was found between the serum glucose level of SGA group (4.03 +/- 1.05 mmol/L) and AGA group (4.05 +/- 1.14 mmol/L), P = 0.008. The serum insulin level (converted into Ln) of SGA group (2.262 +/- 0.746) was significantly higher than that of AGA group (1.757 +/- 0.805), P < 0.001. The HOMA-IR (also converted into Ln) level of SGA group (0.217 +/- 0.367) was also significantly higher than that of AGA group (0.001 +/- 0.378), P < 0.001. In the SGA group beta3-AR gene Arg64 allele carriers had higher serum insulin and HOMA-IR level (both changed to Ln, 2.654 +/- 0.701, 0.371 +/- 0.338) compared with noncarriers (2.074 +/- 0.698, 0.143 +/- 0.360), P < 0.05. The ACE gene DD genotype carriers had higher serum insulin and HOMA-IR level (both were converted into Ln, 2.19 +/- 0.91, 0.51 +/- 1.01) compared with II (1.77 +/- 0.85, 0.02 +/- 0.93) and ID genotype group (1.77 +/- 0.83, 0.05 +/- 0.91), P < 0.05. The ACE gene DD carriers had lower birth weight percentage compared with II and ID genotype group, P < 0.05. When both genes' polymorphisms were taken into account, the newborns who had both DD genotype and Arg64 allele had obviously higher serum insulin level (Ln, 2.560 +/- 1.160) than the neonates who had only one of the polymorphisms mentioned above (1.970 +/- 0.821, 1.992 +/- 0.706) and the neonates who had neither of the two polymorphisms (1.683 +/- 0.832), P < 0.05. The newborns who had both DD genotype and Arg64 allele also had significantly higher HOMA-IR level (Ln, 1.042 +/- 1.315) than the neonates who had only one of the polymorphisms mentioned above (0.247 +/- 0.710, 0.230 +/- 0.890) and the neonates who had neither of the two polymorphisms (-0.053 +/- 0.924), P < 0.05. CONCLUSION: Newborns SGA had impaired insulin sensitivity. beta3-AR gene Trp64Arg polymorphism and ACE gene I/D polymorphism are important factors that may connect IUGR with insulin resistance syndrome in adulthood.