Nationwide surveillance of circulatory collapse associated with levothyroxine administration in very‐low‐birthweight infants in Japan

Background: Although the administration of levothyroxine sodium (LT4) to premature infants had been considered safe, several cases of late‐onset circulatory collapse (LCC) following the administration of LT4 in very‐low‐birth‐weight (VLBW) infants have been reported in Japan since 2008. This study was performed to investigate the incidence of LCC associated with the administration of LT4 to VLBW infants. Methods: A questionnaire regarding LCC with or without an association with LT4 administration in VLBW infants from 2006 to 2008, was sent to 212 hospitals belonging to the Japan Neonatologist Association. Results: Data of 8727 VLBW infants were analyzed, and 46 cases of LCC associated with the administration of LT4 were reported in this surveillance. Especially, an analysis for infants weighing between 1000 and 1499 g at birth revealed that the incidence of LCC with the administration of LT4 was higher than that of those without LT4. Conclusions: LT4 is widely used for infants, including VLBW infants, and no major complications have been reported. However, our study revealed that more than a few cases of LCC were associated with the administration of LT4 in VLBW infants. In conclusion, careful attention is necessary when initiating the administration of LT4 to VLBW infants.     

Hydrocortisone and long‐term outcomes in very‐low‐birthweight infants

Background: The long‐term effects of hydrocortisone (HDC) used for very‐low‐birthweight (VLBW) infants with chronic lung disease (CLD) are not fully understood. The aim of this study was to examine the short‐term clinical effects and long‐term impact of a physiological replacement dose of HDC on acute deterioration of CLD in VLBW infants. Methods: This prospective case–control study included 110 of the 174 VLBW infants admitted to our facility between 2003 and 2006 who were followed up to a corrected age of 18 months. Infant deaths and infants with congenital deformities were excluded from the study. The infants were classified into the following three groups: infants with CLD and treated with HDC (1–2 mg/kg/dose) due to progressive deterioration in oxygenation (CLD treatment group; n= 24); infants with CLD but not treated with HDC (CLD untreated group; n= 40); and infants without CLD (non‐CLD group; n= 46). Results: The fraction of inspired oxygen (F_IO₂) in the CLD treatment group improved significantly after treatment (P < 0.01). There were no significant differences among the three groups in terms of growth and neurodevelopmental quotient at the corrected age of 18 months following adjustment for birthweight, sex, and presence of light‐for‐date infants. There were also no significant intergroup differences in all three areas of developmental quotient. Conclusions: Physiological doses of HDC replacement are effective in treating acute deterioration in oxygenation in VLBW infants with CLD. Furthermore, this treatment modality did not adversely affect the growth and development of infants at the corrected age of 18 months.     

Clinical aspects of very‐low‐birthweight infants showing reopening of ductus arteriosus

Background: Indomethacin is used to treat the hemodynamically significant patent ductus arteriosus in premature infants. Some infants show ductus arteriosus reopening after effective constriction by the drug. The purpose of this study was to examine the clinical characteristics of such infants. Methods: We studied 57 very‐low‐birthweight infants with effective constriction of patent ductus arteriosus by the initial course of indomethacin. They were classified into the reopened group if they developed hemodynamically significant patent ductus arteriosus again or into the closed group if they showed complete closure. Clinical characteristics were compared between the two groups. Results: Ductus arteriosus reopening was shown in 15 (26%) of the 57 infants. These 15 infants had successful clinical ductal closure after a subsequent course of indomethacin or oral mefenamic acid treatment or surgical ligation without any severe complications. Infants in the reopened group showed significantly higher rates of developing chronic lung disease at 36 weeks of gestation than those in the closed group (53% vs 18%; P= 0.009). Furthermore, multivariate logistic regression analysis revealed ductus arteriosus reopening was the only independent risk factor for developing chronic lung disease at 36 postconceptional weeks in this population (adjusted odds ratio, 6.1; 95% confidence interval, 1.4–31.2; P= 0.02). Conclusions: Incomplete closure of the ductus arteriosus is associated with recurrence of a clinically significant patent ductus arteriosus and reopening of the ductus after initial closure with indomethacin is associated with chronic lung disease.     

Outcomes of inborn and transported extremely premature very‐low‐birthweight infants in Hawai‘i

Background: Delivery of premature infants outside tertiary care centers is not always preventable. The aim of this study was to compare rates of survival and common morbidities in extremely premature babies transported to a level III facility versus those born at the level III center. Methods: Retrospective chart review was performed on all neonates born at ≤ 28 weeks of gestation with birthweight ≤1500 g who were admitted to the Newborn Intensive Care Unit at Kapi‘olani Medical Center for Women and Children (KMCWC) between 1 January 2000 and 31 December 2005. Infants were divided into two groups, those born at KMCWC (Inborn) and those born at level I institutions and subsequently transported (Transport) to KMCWC. Results: A total of 394 neonates met the study criteria; 349 were inborn while 45 were transported. Survival rates were identical for both groups. However, the Transport group survivors displayed a significantly longer mean length of stay and higher rate of severe retinopathy of prematurity than those in the Inborn group (P≤ 0.01). Conclusion: Identical rates of survival in both groups suggest that community medical professionals are providing satisfactory care to stabilize critical neonates without reducing their chances of survival. However, increased length of stay and higher rate of retinopathy of prematurity in the Transport group suggest that differences in medical management during the first few hours of life may adversely affect outcomes.     

Outcomes of very‐low‐birthweight infants after discharge with a discharge weight of 1500 grams

Background: Discharge of very‐low‐birthweight (VLBW) neonates from hospital is an important issue and has a standard criterion worldwide. According to this criterion, VLBW infants will be discharged from hospital when weighing 1800–2100 g but in the newborn services at Amirkola Children's Hospital (ACH), VLBW neonates are discharged when reaching 1500 g. The aim of this study was to determine the safety of this policy. Methods: In this analytic‐prospective study, 100 premature neonates with discharging weight (DW) of 1500 g and a control group of 150 neonates with DW of 1600–2500 g were included. Both groups showed similar socioeconomic, perinatal and postnatal conditions. They were admitted and treated in the newborn services at ACH. The outcome variables, including death after discharge, readmission and need for emergency visit for an acute problem up to 3 months after discharge, were studied. The information was analyzed by spss ‐16 software and a P‐value < 0.05 was considered significant. Results: Need for emergency visit after discharge reached a significant difference between the two groups (31 in the case group vs 21 in the control group, P= 0.000), but there were no significant differences in the readmission rate and death after discharge (two deaths and 15 readmissions in the case group vs two deaths and 21 readmissions in the control group, P= 0.855) Conclusion: In order to decrease the need for emergency visits, we suggest a program of early hospital discharge with home nursing visits and neonatologist support.     

Outcomes of very‐low‐birthweight infants at 3 years of age born in 2003–2004 in Japan

Background: The aim of this study was to describe and compare neurodevelopmental outcomes with birthweight (BW) groups at 250‐g intervals of very‐low‐birthweight (VLBW) infants at 3 years of age in a multicenter cohort in Japan. Methods: A total of 3104 VLBW infants born in 2003 and 2004 registered in a NICU‐network database were followed in the study. Neurodevelopmental impairment (NDI) was defined as any of the following impairments: cerebral palsy, unilateral or bilateral blindness, severe hearing impairment, or developmental delay; a developmental quotient (DQ) <70 measured using the Kyoto Scale of Psychological Development test or judged by physicians in infants without the test. Results: A total of 257 infants died and follow‐up data were obtained from 1826 infants. Of the 1826 infants, 155 (8.5%) had cerebral palsy, 25 (1.4%) had visual impairment, and 12 (0.7%) had hearing impairment. Of the 1197 infants in whom DQ was measured, 184 (15.4%) had DQ < 70. The proportion of NDI in the evaluated infants was 19.2% (n= 350), ranging from 11.9% (BW 1251–1500 g) to 42.0% (BW ≤ 500 g). Odds ratios (95%CI) of NDI or death against the group BW 1251–1500 g were 20.62 (13.29–31.97) in BW ≤ 500 g, 7.25 (5.45–9.64) in BW 501–750 g, 2.85 (2.12–3.82) in BW 751–1000 g and 1.18 (0.85–1.64) in BW 1001–1250 g. Conclusion: The increasing proportion of NDI or death, an indicator of adverse outcome, was associated with decrement in the BW of the groups. Although we have to consider a bias due to loss of follow‐up data, the incidence of NDI was similar to previous overseas cohort studies despite the higher survival proportion in our study.     

Availability of donor milk improves enteral feeding but has limited effect on body growth of infants with very‐low birthweight: Data from a historic cohort study

Compare with preterm formula, donor human milk (DM) is associated with a lower risk of mortality and morbidity in preterm infants. It is thus deemed superior to preterm formula as the sole diet or supplement to own mother''s milk (OMM) for preterm infants, especially for those with very low birthweight (VLBW). This historic cohort study investigated the relationship between DM availability, and enteral feeding, body growth of VLBW infants by comparing two cohorts before and after the establishment of a human milk bank. A sub‐analysis was also conducted between small‐for‐gestational‐age (SGA) and non‐SGA infants in our cohorts. Our results showed that DM availability was associated with earlier initiation and faster advancement of enteral feeding, earlier attainment of full enteral feeding, and a higher proportion of OMM in enteral feeding. DM availability was also associated with earlier regain of birthweight, but not with better body growth. SGA and non‐SGA infants responded differently to DM availability with only the non‐SGA group showing improved enteral feeding associated with DM availability. The poor growth of VLBW infants with fortified DM warrants further investigations on better fortification strategies to further improve body growth. Studies are also needed on long‐term effects of DM feeding on the development of VLBW infants.     

Therapeutic strategies of meconium obstruction of the small bowel in very‐low‐birthweight neonates

Background: Meconium obstruction without cystic fibrosis in low‐birthweight neonates is a distinct clinical entity. We aimed to determine what therapeutic strategies work best in very‐low‐birthweight neonates with meconium obstruction of the small bowel under varied clinical conditions caused by the associated diseases of prematurity. Methods: Medical records of very‐low‐birthweight neonates with meconium obstruction of the small bowel treated from 1998 to 2008 were retrospectively reviewed. Pre‐ and postnatal data, treatments, and clinical outcomes were assessed. Results: Nine patients with perinatal complications were identified. Mean gestational age and birthweight were 26.9 weeks and 863 g, respectively. Abdominal distension developed from 1 to 7 days of life. Five patients were initially treated with Gastrografin enema, three of whom had successful outcomes. Two hemodynamically unstable patients failed to respond to Gastrografin treatment; they ultimately died of sepsis. The remaining four without Gastrografin treatment underwent enterostomy to resolve the obstructions with good results. Conclusions: Gastrografin and surgical treatments should be appropriately selected based on the underlying pathologies of meconium obstruction of the small bowel. Therapeutic Gastrografin enema is effective, safe and repeatable; however, it is not recommended for hemodynamically unstable patients. Surgical intervention is reserved for those who develop rapid abdominal distension that risks perforation.     

Mesenteric hernia causing bowel obstruction in very low‐birthweight infants

Internal hernia through a mesenteric defect, called mesenteric hernia, is an uncommon cause of acute intestinal obstruction in newborns. Strangulated mesenteric hernia results in intestinal necrosis or perforation and progressive deterioration with fatal outcome, especially when it occurs in low‐birthweight infants. We report two very low‐birthweight (VLBW) infants, who presented with acute intestinal obstruction related to mesenteric defect. The initial diagnosis was meconium obstruction in those cases, which is a common cause of bowel obstruction occurring in VLBW infants. Correct diagnosis of mesenteric hernia was difficult in these cases because of rapid deterioration and non‐specific radiological findings. Awareness of the possibility of rare mesenteric hernia causing acute intestinal obstruction and surgical intervention in an appropriate timeframe are important for rescuing VLBW infants with such organic abnormalities.     

Predicting factors of plural hospitalization with pneumonia in low‐birthweight infants

Background: Children with a history of low birthweight (LBW) are often hospitalized with plural episodes of pneumonia after discharge from the neonatal intensive care unit. The aim of this study was to clarify the multiple factors predisposing them to developing three or more hospitalizations with pneumonia and whether the factors are related to their own prematurity. We also aimed to determine a predictable numerical formula for three or more episodes. Methods: Fourteen patients with two hospitalizations with pneumonia were grouped into group A. Fourteen patients with at least three episodes during the same investigation period were grouped into group B. The quantification theory type III was employed to investigate the similarities among the items and the gravity of each attribution in the two groups. To evaluate the items of discrimination of both groups, six items were analyzed by the quantification theory type II. Results: The dominant order of items contributing to the grouping was as follows: methicillin‐resistant staphylococcus aureus detection (partial correlation coefficient = 0.5284), asthmatic attack (partial correlation coefficient = 0.4138), severe motor and intellectual disability, Haemophilus influenzae, accompanying diseases and chronic lung disease. A predicting numerical formula was attained from these results. The success rate of discrimination was 85.7%. The six items seemed to be related to the patients' own prematurity. Conclusions: The authors emphasize that plural hospitalizations with pneumonia in the patients with LBW might be caused by the combined influence of six clinical factors as well as their own prematurity.     

Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial

AIM—To investigate the colonisation with Bifidobacterium breve of the bowels of very low birthweight (VLBW) infants.METHODS—The adverse effects of B breve were examined in 66 VLBW infants (preliminary study). A prospective randomised clinical study of 91 VLBW infants was also completed and these infants were followed up for three years. Precise viable bacterial counts of serial stool specimens were examined for the first eight weeks after birth in 10 infants. The colonisation rates of administered bacteria were examined using immunohistochemical staining of stool specimens with a B breve specific monoclonal antibody.RESULTS—In the preliminary study there were no side effects attributable to the bacteria. Immunohistochemical staining of stool specimens showed that the colonisation rates of the administered bacteria were 73% at 2 weeks of age, but only 12% in the control group. Early administration of B breve significantly decreased aspirated air volume from the stomach and improved weight gain.CONCLUSIONS—B breve can colonise the immature bowel very effectively and is associated with fewer abnormal abdominal signs and better weight gain in VLBW infants, probably as a result of stabilisation of their intestinal flora and accelerated feeding schedules.