Efficacy of parent-child interaction therapy for children born premature.

BACKGROUND: Premature children are known to be at a high risk of developing behavioral problems. This study examined the effectiveness of parent-child interaction therapy (PCIT) in reducing behavioral problems in young children born premature. METHODS: The study included 18 child-parent pairs with children born at less than 35 weeks of gestation (range: 23-34 weeks, median: 31.0 weeks) and aged 27-52 months (median: 38.0 months). They were assigned to either the PCIT group (n = 7) or the non-PCIT group (n = 11) based on maternal desire for treatment. The study was designed to examine the effects of PCIT. Specifically, the Eyberg Child Behavior Inventory (ECBI) intensity score, ECBI problem score, and Parenting Stress Index Short Form (PSI-SF) scores were compared before treatment and after 6 months. RESULTS: In the PCIT group, the mean ECBI intensity score was 135.7 (SD = 13.5; T-score = 64) at baseline and 90.1 (SD = 15.5; T-score = 46) at post-assessment, the mean ECBI problem score was 9.8 (SD = 1.9; T-score = 54) at baseline and 4.4 (SD = 3.1; T-score = 44) at post-assessment, the mean PSI-SF total score was 60.1 (SD = 4.8; 95%tile) at baseline and 49.6 (SD = 5.6; 85%tile) at post-assessment, showing a significant improvement (ECBI intensity scores: p < 0.001, d = 2.03; ECBI problem scores: p < 0.001, d = 1.94; PSI-SF total scores: p = 0.004, d = 0.86). On the other hand, none of the scores showed significant change in the non-PCIT group. CONCLUSIONS: The PCIT can be considered as a potential treatment option for behavioral problems in young children born premature.

Neonatal respiratory support related to lung function abnormalities in school-age children with bronchopulmonary dysplasia.

OBJECTIVE: To elucidate the relationship between abnormal lung function (LF) at school age and neonatal respiratory support in very low birth weight children with bronchopulmonary dysplasia (BPD). STUDY DESIGN: We retrospectively examined 78 BPD children whose LF was evaluated at 8-9 years. LF abnormalities were defined by reduced values of spirometric parameters. Adjusted odds ratios (aORs) for abnormal LF by the type and postmenstrual age (PMA) of respiratory support were calculated using logistic regression analysis after controlling perinatal factors. RESULTS: Overall, 24 (31%) patients had LF abnormalities. Antenatal steroid use was associated with a decreased risk of abnormal LF [aOR, 0.31; 95% CI, 0.09-0.92]. Requiring positive-pressure support at 37 weeks' PMA correlated with abnormal LF [aOR, 4.58; 95% CI, 1.15-21.90]; whereas only low-flow oxygen at any PMA did not. CONCLUSION: Requiring positive-pressure support at 37 weeks' PMA could be an indicator of abnormal LF at school age.

A Case of Infantile Mitochondrial Cardiomyopathy Treated with a Combination of Low-Dose Propranolol and Cibenzoline for Left Ventricular Outflow Tract Stenosis.

Hypertrophic cardiomyopathy is a common cardiac complication in mitochondrial disorders, and the morbidity rate in neonatal cases is up to 40%. The mortality rate within 3 months for neonatal-onset mitochondrial cardiomyopathy is known to be high because there is currently no established treatment.We report the case of a male infant with neonatal-onset mitochondrial disorder presenting lactic acidosis and hypertrophic cardiomyopathy. Genetic analysis of the patient revealed recurrent m.13513G>A, p.Asp393Asn in mitochondrially encoded NADH dehydrogenase 5 gene (MT-ND5). Low-dose propranolol was initially administered for cardiomyopathy; however, he developed hypertrophic obstructive cardiomyopathy (HOCM) at 3 months of age. To reduce the risk of hypoglycemia associated with high-dose propranolol, cibenzoline, a class Ia antiarrhythmic drug, was added at a dose of 2.5 mg/kg/day and increased weekly to 7.5 mg/kg/day with monitoring of the blood concentration of cibenzoline. Left ventricular outflow tract stenosis (LVOTS) dramatically improved from 5.4 to 1.3 m/second in LVOTS peak velocity after 6 weeks, without notable adverse effects. The plasma N-terminal pro-brain natriuretic peptide level decreased from 65,854 to 10,044 pg/mL. Furthermore, myocardial hypertrophy also improved, as the left ventricular mass index decreased from 173.1 to 108.9 g/m2 after 3 months of the treatment.The administration of cibenzoline, in conjunction with low-dose propranolol, may serve an effective treatment for HOCM in infantile patients with mitochondrial disorders.

Disseminated intravascular coagulation complicated by amniotic band syndrome associated with deceased fetal umbilical cord following fetoscopic laser surgery.

Fetoscopic laser surgery occasionally causes amniotic band syndrome, in which the disrupted amniotic membrane constricts fetal body parts, leading to functional or morphological loss. We report a case of fetal distress at 31 weeks of gestation in the larger surviving twin after fetoscopic laser surgery for selective intrauterine growth restriction, necessitating emergent cesarean section. Physical examination of the infant showed constriction rings caused by a disrupted amniotic membrane on the digits, and the distal part of the right index finger was necrotic because of tight strangulation by an amniotic band with the umbilical cord of the deceased smaller twin. Laboratory data showed severe coagulopathy, and the infant was diagnosed with disseminated intravascular coagulation (DIC). Immediate treatment improved his condition. DIC may have been associated with the necrotic finger, which was strangulated by the umbilical cord of the deceased fetus, because neither maternal coagulopathy nor an underlying neonatal disorder was detected.

Synergic interaction between ritodrine and magnesium sulfate on the occurrence of critical neonatal hyperkalemia: A Japanese nationwide retrospective cohort study.

Our aim was to evaluate the association between ritodrine and magnesium sulfate (MgSO4) and the occurrence of neonatal hyperkalemia or hypoglycemia among late preterm infants in a retrospective cohort study. We used a nationwide obstetrical database from 2014. A total of 4,622 live preterm infants born at 32-36 gestational weeks participated. Fourteen risk factors based on both clinical relevance and univariate analysis were adjusted in multivariable logistic regression analyses. Neonatal hyperkalemia and hypoglycemia occurred in 7.6% (284/3,732) and 32.4% (1,458/4,501), respectively. Occurrence of hyperkalemia was associated with concomitant usage of ritodrine and MgSO4 compared with no usage (adjusted odds ratio [aOR] 1.53, 95% confidence interval [CI] 1.09-2.15). Occurrence of hypoglycemia was associated with ritodrine alone (aOR 2.58 [CI 2.21-3.01]) and with concomitant usage of ritodrine and MgSO4 (aOR 2.59 [CI 2.13-3.15]), compared with no usage, and was associated with long-term usage (≥ 48 hours) of ritodrine and cessation directly before delivery. In conclusion, in late preterm infants, usage of ritodrine together with MgSO4 was associated with occurrence of critical neonatal hyperkalemia, and long-term usage of ritodrine and cessation directly before delivery were associated with neonatal hypoglycemia.

Takotsubo syndrome occurring concomitantly with pre-eclampsia: A case report.

Takotsubo syndrome (TTS) patients show transient ventricular dysfunction without coronary artery stenosis. We report a pregnant woman with TTS occurring concomitantly with severe pre-eclampsia (PE). A primiparous woman complained of dyspnea at 35 weeks of gestation. She showed severe PE, and cardiac ultrasound identified akinesis of the anterior lower wall. On the same day, emergent cesarean section was performed due to a nonreassuring fetus status, yielding a male infant with an umbilical artery pH of 6.851. Unfortunately, the neonate died of multiple organ failure. Following the delivery, her cardiac function markedly improved, and coronary angiography showed no coronary artery stenosis. Considering the clinical findings, we diagnosed the patient with TTS. Regarding antenatally occurring TTS, only six patients have been reported including the present one. Of the six patients, three had severe PE. Although previous reports on pregnancy-associated TTS described good maternal outcomes, antenatally occurring TTS complicated by severe PE may become critical for fetuses.

Vaginal Ureaplasma species increase chorioamnionitis in very preterm infants with preterm premature rupture of the membranes at < 28 weeks of gestation.

Our aim was to investigate the association between vaginal Ureaplasma species (spp.) and the subsequent occurrence of chorioamnionitis (CAM), perinatal death, neonatal morbidity, and long-term neurodevelopmental impairments (NDIs) at 3 years of age. We analyzed 55 pregnant women with singleton pregnancy who had preterm premature rupture of the membranes (pPROM) at < 28+0 weeks of gestation, and delivered between 22+0 and 31+6 weeks at our tertiary hospital in 2007-2016. NDIs were defined as either cerebral palsy or developmental delay evaluated at 1.5 and/or 3 years old. The presence of Ureaplasma spp. and Mycoplasma hominis were evaluated using urea-arginine broth and Mycoplasma PPLO Agar. The presence of Ureaplasma spp. in the vagina was positive in 41%. Vaginal Ureaplasma spp. was a significant risk factor for CAM; however, it was not significantly associated with the occurrence of perinatal death, pulmonary hypoplasia, respiratory distress syndrome, transient tachypnea of the newborn, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia defined as oxygen required and occasional ventilatory assistance required at week 36 as modified (BPD36), or NDIs. The crude odds ratio (95% confidence interval) of Ureaplasma spp. for the occurrence of CAM was 9.5 (1.10-82) (p = 0.041). In very preterm birth infants with pPROM, CAM, BPD36, and NDIs occurred in 78, 60, and 36%, respectively. Vaginal Ureaplasma spp. was a significant risk factor for CAM in very preterm birth infants with pPROM. The incidences of BPD36 and NDIs in such infants were very high, nearing 3/5 and 1/3, respectively.

Neonatal factors related to center variation in the incidence of late-onset circulatory collapse in extremely preterm infants.

BACKGROUND: Although late-onset circulatory collapse (LCC) is widely recognized in Japan, its etiology and the reason for center variation in its incidence remain unclear. This study's objectives were to identify the perinatal and neonatal factors related to LCC and to estimate the factors related to the center variation in the incidence of LCC. METHODS: Extremely preterm infants born between 2008 and 2012 who were registered in the database of the Neonatal Research Network, Japan were retrospectively analyzed. LCC was defined as a clinical diagnosis of LCC and the administration of steroids. We first identified the factors that were significantly related to LCC. We then examined the cause of the center variation in the incidence of LCC, using the standardized incidence ratios (SIRs) of LCC and individual factors. RESULTS: The factors significantly associated with LCC included low gestational age (odds ratio [OR]: 1.13), small for date (OR: 1.43), male sex (OR: 1.26), antenatal steroid use (OR: 1.19), respiratory distress syndrome (OR: 1.25), chronic lung disease at 36 weeks (OR: 1.16), periventricular leukomalacia (PVL) (OR: 2.57), necrotizing enterocolitis (OR: 0.59), retinopathy of prematurity (ROP) (OR: 1.73), high-frequency oscillating ventilation (HFOV) use (OR: 1.31), parenteral nutrition (OR: 1.38), and red blood cell (RBC) transfusion (OR: 1.94). The SIR of LCC ranged from 0.05 to 2.94, and was positively correlated with SIRs of PVL, ROP, HFOV use and RBC transfusion. CONCLUSION: PVL, ROP, HFOV use and RBC transfusion were found to be correlated with the center variation in the incidence of LCC.

Pelizaeus-Merzbacher disease can be a differential diagnosis in males presenting with severe neonatal respiratory distress and hypotonia.

Pelizaeus-Merzbacher disease (PMD; MIM #312080) is a rare X-linked recessive disorder. A male neonate presented with severe respiratory distress that required tracheostomy. After the appearance of nystagmus, PMD was suspected as a diagnosis for the patient, and a missense mutation, p.Phe51Val, was identified in PLP1, the gene responsible for PMD. PMD can be a differential diagnosis in a male neonate presenting severe respiratory distress.

Hyperinsulinemic hypoglycemia in Beckwith-Wiedemann, Sotos, and Kabuki syndromes: A nationwide survey in Japan.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.

Cytokine profile in two siblings with neonatal lupus erythematosus.

We studied the cytokine profile of two siblings with neonatal lupus erythematosus (NLE) born to a mother positive for serum anti-Ro and -La antibodies, who did not receive any medication during the two pregnancies. The first sibling was found to have complete atrioventricular block in utero and became severely ill after birth. He fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis on day 2. The second sibling did not have any fetal symptoms. He was generally stable after birth, but with typical skin rash. Laboratory data suggested that they both had hypercytokinemia during the neonatal period, requiring corticosteroid treatment. Interleukin (IL)-6, interferon-γ, IL-8 and monocyte chemotactic protein-1 were elevated in both cases, while IL-12, IL-13 and IL-17 were elevated only in the second sibling. Comparison of the cytokine profiles suggests the potential roles of different cytokines in the onset and clinical manifestations of NLE.

Constitutively high-level expression of TGFß isoforms in cord blood and its relationship to perinatal findings.

BACKGROUND: The clinical significance of TGFß isoforms in cord blood is not well understood. METHODS: We obtained cord blood samples from 37 term infants and 85 preterm infants who were born in several clinical settings. The serum levels of 3 TGFß isoforms and of the other 17 cytokines in cord blood were investigated using cytometric bead array technology. RESULTS: Very high levels of TGFß1 and TGFß2 isoforms compared to the level of other cytokines were found; mean levels were 44,180 and 1871pg/mL, respectively. The levels of all 3 isoforms of TGFß were significantly correlated with birth weight, and the levels of TGFß1 and TGFß3 were correlated with gestational age. The levels of TGFß1 and ß2 isoforms were strongly correlated with each other, but not with levels of other cytokines. The levels of TGFß1 and TGFß2 were significantly higher in male infants and significantly lower in infants with fetal growth restriction. The prevalence of chronic lung disease was related to a low level of TGFß1, and that of patent ductus arteriosus was related to a high level of TGFß1 in preterm infants. CONCLUSIONS: TGFß1 and TGFß2 appeared to play a significant role in physiological and pathological conditions in the fetus. TGFß isoform levels appear to be regulated independently of those of other cytokines and do not appear to be influenced by inflammation in the fetal period. The role of TGFß3 in cord blood and the postnatal chronological changes of the TGFß isoforms should be investigated in the future.

Gut hormones of preterm infants with abdominal symptoms and hypothyroxinemia.

BACKGROUND: The pathogenesis of abdominal symptoms in premature infants with hypothyroxinemia is not understood; therefore, we investigated changes in gut hormones before and after levothyroxine sodium (T4-Na) supplementation in preterm infants with abdominal symptoms and hypothyroxinemia. METHODS: In eight preterm study subjects and 14 gestational age-matched controls, fasting serum concentration of leptin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide, insulin, amylin and ghrelin was measured using a bead array system. RESULTS: Serum GLP-1, GIP and PYY in the subjects before T4-Na supplementation were lower than in controls at age 2 weeks. After improvement of abdominal symptoms and free thyroxine, serum levels of the three gut hormones in the subjects were increased and were not different from those in the control patients. CONCLUSIONS: In preterm infants with abdominal symptoms, serum GLP-1, GIP and PYY might be related to thyroid function.

Gut hormone profiles in preterm and term infants during the first 2 months of life.

AIM: To investigate changes of gut hormones in term and preterm infants in the first 2 months after birth, as the role and relationships of gut hormones in premature infants has not been well elucidated. METHODS: In 29 preterm and five term infants, fasting serum concentrations of leptin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide, insulin, amylin, and ghrelin were measured using a bead array system. RESULTS: Serum leptin concentration soon after birth showed a positive correlation with gestational week in all infants (r=0.623, p<0.01). Serum leptin level rapidly decreased in all infants. In preterm infants, serum GLP-1 levels at birth showed negative correlations with gestational week (r=-0.447, p=0.02). Serum GIP, GLP-1, and PYY levels increased after birth and were persistently high until 10 weeks of life. CONCLUSION: Serum concentrations of different gut hormones changed postnatally in their specific ways in preterm infants.

Williams-Beuren syndrome with brain malformation and hypertrophic cardiomyopathy.

Williams-Beuren syndrome (WBS) is a multisystemic genetic disorder caused by a contiguous gene deletion at 7q11.23. We report a severely affected WBS patient with cerebral and cerebellar dysplasia as well as hypertrophic cardiomyopathy. Microarray comparative genomic hybridization (aCGH) detected a deletion on 7q11.23 expanding from RP11-614D7 to RP11-137E8, which is a typical deletion in WBS. To the best of our knowledge, this is the first case report of a WBS patient with severe congenital central nervous system anomaly and progressive hypertrophic cardiomyopathy. The relationship between the genes deleted in WBS and a CNS anomaly plus hypertrophic cardiomyopathy requires further analysis.

Ash1l methylates Lys36 of histone H3 independently of transcriptional elongation to counteract polycomb silencing.

Molecular mechanisms for the establishment of transcriptional memory are poorly understood. 5,6-dichloro-1-D-ribofuranosyl-benzimidazole (DRB) is a P-TEFb kinase inhibitor that artificially induces the poised RNA polymerase II (RNAPII), thereby manifesting intermediate steps for the establishment of transcriptional activation. Here, using genetics and DRB, we show that mammalian Absent, small, or homeotic discs 1-like (Ash1l), a member of the trithorax group proteins, methylates Lys36 of histone H3 to promote the establishment of Hox gene expression by counteracting Polycomb silencing. Importantly, we found that Ash1l-dependent Lys36 di-, tri-methylation of histone H3 in a coding region and exclusion of Polycomb group proteins occur independently of transcriptional elongation in embryonic stem (ES) cells, although both were previously thought to be consequences of transcription. Genome-wide analyses of histone H3 Lys36 methylation under DRB treatment have suggested that binding of the retinoic acid receptor (RAR) to a certain genomic region promotes trimethylation in the RAR-associated gene independent of its ongoing transcription. Moreover, DRB treatment unveils a parallel response between Lys36 methylation of histone H3 and occupancy of either Tip60 or Mof in a region-dependent manner. We also found that Brg1 is another key player involved in the response. Our results uncover a novel regulatory cascade orchestrated by Ash1l with RAR and provide insights into mechanisms underlying the establishment of the transcriptional activation that counteracts Polycomb silencing.

Maternal Perception of Decreased Fetal Movement in One Twin: A Clue Leading to the Early Detection of Absent Variability due to Acute Twin-to-Twin Transfusion Syndrome.

Decreased fetal movement (DFM) perceived by pregnant women sometimes indicates imminent fetal jeopardy. It is unknown whether this also holds true for twin pregnancy. A 27-year-old primiparous woman with monochorionic diamniotic (MD) pregnancy had a slight difference of amniotic fluid volume at 31(2/7) weeks of gestation. DFM only in one twin at 31(4/7) weeks of gestation prompted her to receive urgent consultation. Since cardiotocogram indicated absent variability of one twin, we performed Cesarean section. Male infants weighing 2060 g and 1578 g were delivered; hemoglobin was 20.7 versus 10.8 g/dL, respectively; cardiothoracic ratio was 70% versus 44%, respectively, indicating acute twin-to-twin transfusion syndrome (TTTS). The recipient infant had heart failure, which was still observed at 1 month postpartum. In conclusion, maternal perception of DFM indicated imminent fetal death or jeopardy caused by acute TTTS, suggesting that education regarding DFM for women with twin pregnancy may be clinically important.

Do neonates conceived after assisted reproductive technology require neonatal surgery more frequently? A 5-year single-center experience.

AIM: Assisted reproductive technology (ART) has increased the incidences of multiple gestations and low birth weights, which frequently warrant pediatric surgery. ART may have also increased the rate of birth defects. In this study, we aimed to determine whether infants conceived after ART required neonatal surgery more frequently compared with naturally conceived infants. MATERIAL AND METHODS: Our study population comprised 1891 infants (160 ART (+) and 1731 ART (-)) who were admitted to our neonatal intensive care unit during a 5-year period (January 2006-December 2010); of these, 198 infants (9 ART (+) and 189 ART (-)), with diseases requiring surgery, were referred to pediatric surgeons (consultation cases). We examined the following: (i) factors potentially increasing the requirement for surgery; (ii) frequency of birth defects; and (iii) maternal factors that may increase the need for surgery. RESULTS: A significantly higher incidence of multiple gestation and low birth weight was observed in the ART (+) group than the ART (-) group. However, ART did not yield a higher rate of surgery and birth defects: overall, the rate of surgery was 4% (7/160) in the ART (+) group and 8% (143/1731) in the ART (-) group. Of 198 consultation cases, the percentage of infants actually requiring surgery was approximately the same in the ART (+) group (7/9 [78%]) and the ART (-) group (143/189 [76%]). CONCLUSION: Infants conceived after ART comprised a small proportion of neonatal surgery cases, and did not require surgery more frequently.