Investigation of (Epi)genetic causes in syndromic short children born small for gestational age.

Intrauterine onset syndromic short stature constitutes a group of diseases that pose challenges in differential diagnosis due to their rarity and clinical as well as molecular heterogeneity. The aim of this study was to investigate the presence of (epi)genetic causes in children born small for gestational age (SGA) and manifesting clinically undiagnosed syndromic short stature. The study group comprised twenty-nine cases selected from the syndromic SGA cohort. Various analyses were performed, including chromosomal microarray (CMA), methylation-specific-multiple ligation probe amplification for chromosomes 6,14 and 20, and whole exome sequencing (WES). Pathogenic copy number variants (CNVs) on chromosomes 2q13, 22q11.3, Xp22.33, 17q21.31, 19p13.13 and 4p16.31 causing syndromic growth disturbance were detected in six patients. Maternal uniparental disomy 14 was identified in a patient. WES was performed in the remaining 22 patients, revealing pathogenic variants in nine cases; six were monoallelic (ACAN, ARID2, NIPBL, PIK3R1, SMAD4, BRIP1), two were biallelic (BRCA2, RFWD3) and one was hemizygous (HUWE1). Seven of these were novel. Craniofacial dysmorphism, which is an important clue for the diagnosis of syndromes, was very mild in all patients. This study unveiled, for the first time, that ARID2 mutatios can cause syndromic SGA. In conclusion, a high (55.2%) diagnosis rate was achieved through the utilization of CMA, epigenetic and WES analyzes; 15 rare syndromes were defined, who were born with SGA and had atypical and/or mild dysmorphic findings. This study not only drew attention to the association of some rare syndromes with SGA, but also introduced novel genes and CNVs as potential contributors to syndromic SGA.

Evaluation of Short-Term Outcomes of Preterm Infants in 2 Periods: Vermont Oxford Network Results of a Developing Country's Single- Center Level IIIC Neonatal Intensive Care Unit Experience.

OBJECTIVE: This study aimed to compare the short-term outcomes of infants from our level IIIC neonatal intensive care unit in 2 different periods. MATERIALS AND METHODS: In this cohort study, data from preterm infants (≤29 weeks and birth weight <1500 g) registered in the Vermont Oxford Network system were divided into 2 periods, the first period between January 1, 2005, and December 31, 2009, and the second between January 1, 2010, and December 31, 2019. RESULTS: There was no difference in the distribution of preterm infants according to their gestational age subgroups (P = .169). Although the survival rate increased significantly in the second period (48.1% vs. 64.3% (P < .001), there was no difference in terms of survival without morbidity (P = .480). The frequency of antenatal care (P < .001), antenatal maternal steroid use (P < .001), cesarean section (P = .025), and small for gestational age (P < .003) increased in the second period. Surfactant treatment in the delivery room (P < .003), neonatal intensive care unit (P < .001), and nasal continuous positive airway pressure use before intubation as a part of initial resuscitation (P < .001), nosocomial infections (P = .001), patent ductus arteriosus requiring medical treatment (P = .011), and necrotizing enterocolitis (P = .014) were significantly more common, but early neonatal sepsis (P = .002) and discharge home with only formula (P = .010) were less in the second period. CONCLUSION: Differences were noted in the prognosis and treatment choices of preterm infants in the same unit between 2 periods. The analysis of neonatal intensive care unit data, through rigorous methods, may provide opportunities for the development of quality improvement projects to improve the quality of health care in developing countries.

The Methylation Status in the Chromosome 11p15.5 Region and Metabolic Disorders in Children with Syndromic and Nonsyndromic Intrauterine Growth Restriction.

Loss of methylation (LoM) of the imprinting control region 1 (ICR1) in the chromosome 11p15.5 domain is detected in patients with Silver-Russell syndrome (SRS), characterized by asymmetric pre- and postnatal growth restriction, and typical craniofacial features. The patients with intrauterine growth restriction (IUGR) possess a high risk for adult metabolic problems. This study is aimed to investigate the methylation levels of the chromosome 11p15.5 region and metabolic problems in children with syndromic and nonsyndromic IUGR. Methylation analysis was performed for chromosome 11p15.5 in 49 patients (33 with suspected SRS and 16 nonsyndromic IUGR) with Netchine-Harbison clinical scoring (NHCS); uniparental disomy for chromosomes 6, 7, 14, and 20 was evaluated for those who were negative. LoM of ICR1 was detected in 14 of 33 suspected SRS patients with 3 or more criteria of NHCS, 5 had borderline LoM. Maternal uniparental disomy of the chromosomes 7 and 14 was found in 2 patients. The overall detection rate of SRS was 45.5%. While clinical findings were similar in patients with LoM and borderline LoM of ICR1, typical craniofacial findings were significantly less in the patients with normal methylation. Methylation patterns were not found to be impaired in the nonsyndromic IUGR group. Metabolic complications were evaluated in a total of 63 patients including 33 SRS-suspicious, 16 nonsyndromic IUGR, and 14 patients with 3M or SHORT syndrome. Increased rates of hypercalciuria, insulin resistance, and dyslipidemia were detected in patients with both syndromic and nonsyndromic IUGR. We would like to emphasize that detecting typical facial findings is effective in the diagnosis of SRS and paying attention to metabolic problems in the follow-up of patients with IUGR is recommended.

Natural history of facial and skeletal features from neonatal period to adulthood in a 3M syndrome cohort with biallelic CUL7 or OBSL1 variants.

3M syndrome is characterized by severe pre- and post-natal growth restriction, typical face, slender tubular bones, tall vertebral bodies, prominent heels and normal intelligence. It is caused by biallelic variants of CUL7, OBSL1 and, more rarely, CCDC8. The aim of this study is to evaluate facial and skeletal findings in 3M patients from neonatal period to adulthood. A total of 19 patients with a median age of diagnosis of 9.2 months were included in this study and were followed for two to 20 years. CUL7 and OBSL1 variants were found in 57.9% and 42.1% of patients, respectively, five of which are novel. Most of patients had triangular face, frontal bossing, short fleshy nose, full fleshy lower lip, transverse groove of rib cage, hyperlordosis and prominent heels. Three new early-diagnostic signs were observed in infants; two were infraorbital swelling of the lower lid and facial infantile hemangioma, both of which became less pronounced with aging. The third was the central tubercle of the upper lip that became more prominent with in time. While slender long bones did not change with aging, the tall vertebral bodies became more prominent radiologically. The mean birth length in patients was -4.3 SDS. Eight patients reached a mean final height of -4.9 SDS. Despite described growth hormone (GH) insensitivity in 3M syndrome, 12 patients either with GH deficiency or with normal GH levels were treated with GH; seven patients responded with an increase in height SDS. This study not only provided early diagnostic signs of the syndrome, but also presented important follow-up findings.

Severe lactic acidosis in an extremely low birth weight infant due to thiamine deficiency.

BACKGROUND: In this case report, we present a preterm newborn with persistent lactic acidosis who received total parenteral nutrition (TPN) that lacked thiamine. CASE PRESENTATION: A 28-week-old, 750 g female infant was born with an Apgar score of 8 at the 5th minute. Umbilical cord blood gas levels, including lactate level, were normal, and she was admitted to our neonatal intensive care unit (NICU). Achieving full enteral feeding was not possible due to gastric residues and abdominal distention, making the patient dependent on TPN during the first 2 weeks of life. An insidious increase in lactic acid levels and uncompensated metabolic acidosis were apparent from the 23rd day of life. Severe metabolic acidosis was persistent despite massive doses of bicarbonate. The acidosis resolved dramatically within 6 h when the patient was administered with thiamine. CONCLUSIONS: Although TPN is life saving in the NICU, meticulous attention must be paid to provide all essential macro- and micro-nutrients.

A rare and emerging pathogen: Raoultella planticola identification based on 16S rRNA in an infant.

Raoultella planticola is rarely associated with clinical infection, and a limited number of pediatric cases have been reported. Herein we report a case of bacteremia presumptively secondary to bilateral conjunctivitis in an infant caused by R. planticola which was successfully treated with piperacillin-tazobactam. It should be kept in mind that R. planticola can be a pathogen in pediatric age groups.

Persistent hyperglycemia in a neonate: Is it a complication of therapeutic hypothermia?

Özdemir H, Memisoglu A, Alp-Unkar Z, Arcagök B, Bilgen H, Turan S, Özek E. Persistent hyperglycemia in a neonate: Is it a complication of therapeutic hypothermia? Turk J Pediatr 2017; 59: 193-196. The aim of this report is to present a newborn with persistent hyperglycemia requiring insulin therapy as a possible complication of therapeutic hypothermia. A term appropriate for gestational age (AGA) female infant, was born by emergency cesarean section due to abruption of placenta and was resuscitated and intubated in the delivery room. Whole body cooling was initiated according to standard cooling criteria. The patient`s blood glucose increased up to 250 mg/dl on a glucose perfusion rate of 6 mg/kg/min after the second day of cooling. Insulin therapy was started due to persistent hyperglycemia and continued for 17 days. As it has been reported in adults after therapeutic cooling, persistent hyperglycemia attributed to hypothermia can also complicate therapeutic hypothermia in neonates.

Ductal closure with intravenous paracetamol: a new approach to patent ductus arteriosus treatment.

OBJECTIVES: Indomethacin and ibuprofen are commonly used in the treatment of hemodynamically significant patent ductus arteriosus (hsPDA). These drugs are associated with serious adverse events, including gastrointestinal perforation, renal failure and bleeding. The role of paracetamol has been proposed for the treatment of PDA. METHODS: We report a series of 11 neonates (birth weight: 415-1580 g; gestational age: 23-30.3 weeks) who were treated with paracetamol for a hsPDA. Neonates with hsPDA were treated with paracetamol in the presence of contraindications to ibuprofen or indomethacin. The condition of significant PDA was defined by the presence of at least one of the following criteria: internal ductal diameter # 1.4 mm/kg body weight, left atrium (LA)-to-aortic (Ao) root ratio > 1.4, unrestrictive pulsatile transductal flow, reverse or absent diastolic flow in the descending aorta along with clinical findings. Intravenous (IV) paracetamol was given at doses 15 mg/kg every 6 h for three days. RESULTS: Successful ductal closure was achieved in 10 out of 11 babies (90.9%). No adverse or side effects were observed during the treatment. CONCLUSIONS: On the basis of these results, paracetamol could be considered as a promising and safe therapy for the treatment of PDA in preterm infants.