Analysis of In-hospital Neonatal Death in the Tertiary Neonatal Intensive Care Unit in China: A Multicenter Retrospective Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Globally, the proportion of child deaths that occur in the neonatal period remains a high level of 37-41%. Differences of cause in neonate death exist in different regions as well as in different economic development countries. The specific aim of this study was to investigate the causes, characteristics, and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.</p><p><b>METHODS</b>All the dead neonates admitted to 26 NICUs were included between January l, 2011, and December 31, 2011. All the data were collected retrospectively from clinical records by a designed questionnaire. Data collected from each NICU were delivered to the leading institution where the results were analyzed.</p><p><b>RESULTS</b>A total of 744 newborns died during the 1-year survey, accounting for 1.2% of all the neonates admitted to 26 NICUs and 37.6% of all the deaths in children under 5 years of age in these hospitals. Preterm neonate death accounted for 59.3% of all the death. The leading causes of death in preterm and term infants were pulmonary disease and infection, respectively. In early neonate period, pulmonary diseases (56.5%) occupied the largest proportion of preterm deaths while infection (27%) and neurologic diseases (22%) were the two main causes of term deaths. In late neonate period, infection was the leading cause of both preterm and term neonate deaths. About two-thirds of neonate death occurred after medical care withdrawal. Of the cases who might survive if receiving continuing treatment, parents' concern about the long-term outcomes was the main reason of medical care withdrawal.</p><p><b>CONCLUSIONS</b>Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age. Our study showed the majority of neonate death occurred in preterm infants. Cause of death varied with the age of death and gestational age. Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical decision.</p>

Mortality and Morbidity of Extremely Low Birth Weight Infants in the Mainland of China: A Multi-center Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>With the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China.</p><p><b>METHODS</b>All infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors.</p><p><b>RESULTS</b>A total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization.</p><p><b>CONCLUSIONS</b>Our study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.</p>

Effects of extensively hydrolyzed protein formula on feeding and growth in preterm infants: a multicenter controlled clinical study / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of extensively hydrolyzed protein formula (eHF) on the feeding and growth in preterm infants through a multicenter controlled clinical study.</p><p><b>METHODS</b>Preterm infants admitted to eight upper first-class hospitals in China between February 2012 and December 2013 were randomly selected. They were divided into two observation groups and two control groups. The first observation group consisted of preterm infants with a gestational age of <32 weeks, who were fed with eHF for 10-14 days after birth and then with standard preterm formula (SPF) until discharge. The second observation group consisted of preterm infants with a gestational age of 32-34 weeks, who were fed with SPF after birth, but were switched to eHF (7-14 days) if suffering feeding intolerance at 6-8 days after birth. The two control groups with corresponding gestational ages kept to be fed with SPF after birth. Clinical data were recorded to compare feeding condition, physical growth, blood biochemical indices, and major complications between different groups.</p><p><b>RESULTS</b>A total of 328 preterm infants were enrolled. Preterm infants with a gestational age of <32 weeks in the observation group had a significantly shorter meconium evacuation time than in the corresponding control group (P<0.05). They also had significantly lower levels of serum total bilirubin at weeks 1 and 2 after birth compared with the control group (P<0.05). The observation group needed more time in reaching enteral nutrition (EN) basic energy uptake of 50 kcal/(kg·d), partial parenteral nutrition (PPN), hospitalization, and corrected gestational age at discharge compared with the controlled infants (P<0.05). There was no difference in the incidence of extrauterine growth retardation (EUGR) at discharge between the two groups (P>0.05). Preterm infants with a gestational age of 32-34 weeks in the observation group had significantly lower serum total bilirubin levels at 2 weeks after birth compared with the corresponding control group (P<0.05). They required more time in achieving EN basic energy and PPN than in the control group (P<0.05). There was no difference in the incidence of EUGR at discharge between the two groups (P>0.05).</p><p><b>CONCLUSIONS</b>For preterm infants, eHF can improve gastrointestinal motility, accelerate bilirubin metabolism and excretion and does not increase the incidence of EUGR.</p>

Role of minocycline in an immature rat model of hypoxic-ischemic brain damage / 中华儿科杂志

<p><b>OBJECTIVE</b>To establish a model of immature rat hypoxic-ischemic brain damage (HIBD) which was expected to be similar to periventricular leukomalacia in human preterm infants pathologically and neuroethologically, and to investigate the role of minocycline (MN) in this model.</p><p><b>METHOD</b>Totally 192 Sprague-Dawley rats (postnatal day 2, P(2)), of either sex, were randomly divided into 4 groups: normal-group, sham operation group, HIBD-group, HIBD + MN group, each group had 48 rats. HIBD group and HIBD + MN group survived the left common carotid artery (CCA) ligation followed by 4h exposure to 8% O(2). Rats in sham operation group only survived the left CCA isolation. Rats in normal group were not treated with anything. In HIBD + MN group, the rats were treated with intraperitoneal injection of minocycline 45 mg/kg, immediately after HI and every 24 h for 2 days. Brain tissues were collected on day 3, 1 week, 2 weeks, 4 weeks after HI, for hematoxylin-eosin staining and histological scoring. Frozen sections of the brains were stained with anti-O4, anti-O1 immunohistochemistry on day 3 after HI, and MBP immunohistochemistry 2 weeks after HI. Rats in the four groups underwent neuroethologic examination 4 weeks after HI.</p><p><b>RESULT</b>In the HIBD group, there were pathological changes in the periventricular white matter. The pathological changes were milder in HIBD + MN group; There was no statistically significant difference between the normal group and HIBD + MN group in the number of positively stained O4 cell (P > 0.05). The number of positively stained O4 cell in the HIBD group was significantly reduced, compared with that of normal group, sham operation group, and HIBD + MN group (23.67 ± 12.00 vs. 52.89 ± 10.68, 39.28 ± 11.78, 41.63 ± 8.41, P < 0.05). The differences in the number of positively stained O1 cell among the normal group, sham operation group, HIBD group and HIBD + MN group had no statistical significance (P = 0.093). The numbers of myelin basic protein (MBP) positively immunostained fiber bundles in the HIBD + MN group were significantly less than that of the normal group and sham operation group (P < 0.05). The numbers of MBP positively immunostained fiber bundles in the HIBD group were significantly less than that of the normal group, sham operation group, and HIBD + MN group (14.71 ± 7.42 vs. 36.67 ± 6.50, 35.50 ± 3.24, 26.33 ± 5.92, P < 0.05). The HIBD group had long-term neuroethologic abnormality. There was no statistically significant difference in the inclined plane test, hanging test and cylinder test among the HIBD + MN group, normal group, and sham operation group (P > 0.05). The scores of the HIBD group had statistical significantly among the normal group, sham operation group and HIBD + MN group (P < 0.05). In the open field test, there was no statistically significant difference between the HIBD group and HIBD + MN group (P = 0.772), but there was significant difference between these two groups and the normal group, sham operation group (P < 0.05).</p><p><b>CONCLUSION</b>Minocycline protects the pre-oligodendrocyte and has protective effects in terms of long-term neuroethology.</p>

A follow-up study on children conceived through intracytoplasmic sperm injection / 中华流行病学杂志

Objective To investigate the perinatal complications, birth defects and growth of children conceived through intracytoplasmic sperm injection (ICSI). Methods A total of 575 children conceived by ICSI in our reproductive medical center, were studied. The follow-up study would include items as pregnant complications, neonatal complications, birth defects in perinatal period, subsequently detected birth defects, body weight and body length/height growth. Results Prematurity and low birth weight of ICSI children were higher in the multiple births than in the singleton births. The rates of materal gestational hypertension, neonatal asphyxia, respiratory distress syndrome, infection diseases were higher in the multiple pregnancies than in the singleton pregnancies(P＜0.05). Eleven ICSI children had died. Ten of them died in the neonatal period and they were preterm infants. One fullterm singleton ICSI child died of hepatoblastoma at the age of 2. The rate of birth defects in perinatal period was higher in ICSI children of multiple pregnancies than in the general population (P＜0.05). The body weight and body length/height of most ICSI children had obtained the standard range between 1 to 3 year-olds. Conclusion The higher rates of perinatal complications in ICSI children were closely related to multiple pregnancies.

Long-term effects of early hyperbaric oxygen therapy on neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

<p><b>OBJECTIVE</b>The application and therapeutic effect of hyperbaric oxygen (HBO) in hypoxic-ischemic brain damage (HIBD) remains controversial. Previous studies have focused on the early pathological and biochemical outcomes and there is a lack of long-term functional evaluation. This study was designed to evaluate the long-term pathological and behavioral changes of early HBO therapy on neonatal rats with HIBD.</p><p><b>METHODS</b>Postnatal 7 days (PD7) rat pups were randomly assigned into Control (n=18), HIBD (n=17) and HBO treatment groups (n=17). HIBD was induced by ligating the left common carotid, followed by 2 hrs hypoxia exposure in the HIBD and HBO treatment groups. The Control group was sham-operated and was not subjected to hypoxia exposure. The HBO therapy with 2 atmosphere absolutes began 0.5-1 hr after HIBD in the HIBD treatment group, once daily for 2 days. The spatial learning and memory ability were evaluated by the Morris water maze test at PD37 to PD41. The morphological and histological changes of the brain, including brain weight, survival neurons, AchE positive unit and NOS positive neurons in hippocampal CA1 region, were detected at PD42.</p><p><b>RESULTS</b>The rats in the HIBD group displayed significant morphological and histological deficits, as well as severe spatial learning and memory disability. In the Morris water maze test, the mean escape latency were longer (56.35 +/- 22.37 s vs 23.07 +/- 16.28 s; P < 0.05) and the probe time and probe length were shorter in the HIBD group (29.29 +/- 6.06 s vs 51.21 +/- 4.59 s and 548 +/- 92 cm vs 989 +/- 101 cm; both P < 0.05) compared with the Control group. The left brain weight in the HIBD group was lighter than that in the Control group (0.601 +/- 0.59 g vs 0.984 +/- 0.18 g; P < 0.05). The survival neurons in the hippocampal CA1 region were less (100 +/- 27/mm vs 183 +/- 8/mm; P < 0.05), as well as the AchE-positive unit and NOS-positive neurons (18.50 +/- 2.24% vs 27.50 +/- 2.18% and 19.25 +/- 4.33 vs 33.75 +/- 5.57 respectively; P < 0.05) after HIBD. Early HBO treatment improved the abilities of spatial learning and alleviated the morphological and histological damage. The mean escape latency (39.17 +/- 21.20 s) was shortened, the probe time (36.84 +/- 4.36 s) and the probe length (686 +/- 76 cm) were longer, and the brain weight (0.768 +/- 0.85 g), the survival neurons (133 +/- 25/mm) and the AchE-positive unit (21.94 +/- 2.73%) increased significantly compared with those of the HIBD group (P < 0.05).</p><p><b>CONCLUSIONS</b>Early HBO treatment resulted in a protective effect against HIBD-induced long-term brain morphological and histological deficits and spatial learning and memory disability.</p>

Influence of methylphenidate on growth of school age children with attention deficit hyperactivity disorder / 中华儿科杂志

<p><b>OBJECTIVE</b>To determine whether long-term treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate influences the growth in height and weight of children.</p><p><b>METHODS</b>Analyses were performed on 146 school age children (126 boys) diagnosed as ADHD and treated with methylphenidate [0.27-0.64 mg/(kg.day)] for methylphenidate group and 29 children with ADHD who did not receive any medication for ADHD (controls). These children were followed-up for 2-4 years. Changes in height and weight after long-term treatment with methylphenidate were recorded and the factors affecting growth of height, weight, and height velocity were analyzed.</p><p><b>RESULTS</b>The change of difference between patients' height and mean height in methylphenidate group and controls was (-1.86 +/- 0.82) cm (paired t test, t = 27.335, P < 0.001) and (-0.26 +/- 0.51) cm (P < 0.05), respectively; the change of height standard deviation score (SDS) in methylphenidate group and controls was -0.14 +/- 0.23 SD (paired t test, t = 7.326, P < 0.001) and +0.05 +/- 0.10 SD (P < 0.05), respectively. When the height change and height SDS change in methylphenidate group and controls were compared by using independent-samples T-test, the t value was -10.078 and -4.262 respectively, P for both was < 0.001. Both of bivariate correlation analysis and stepwise multiple-regression analysis indicated that the duration of treatment contributed significantly to the variance in change of height (P < 0.001); but age, sex, DSM-IV type, NJ22 degree and dose of methylphenidate did not contribute significantly to the variance of height. The mean height velocity from 1st to 4th year was 4.28 cm/year, 4.90 cm/year, 4.98 cm/year and 4.95 cm/year, respectively. With Friedman test, Chi-square = 253.673, P < 0.001. The change of difference of patients' weight to weight for height after methylphenidate was (-0.14 +/- 1.25) kg (paired t test, t = 1.326, P > 0.05).</p><p><b>CONCLUSION</b>Small but significant deceleration of height velocity is the identified long-term side effect of methylphenidate, the magnitude of height deficit is related to duration of treatment. The height velocity was significantly attenuated in the first year. Methylphenidate had no significant influence on weight.</p>

Long-term effects of delayed hyperbaric oxygen therapy on hypoxic-ischemic brain injury in neonatal rats / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the long-term effects of delayed hyperbaric oxygen (HBO) therapy on neonatal rats with hypoxic-ischemic brain injury (HIBD).</p><p><b>METHOD</b>Postnatal 7 days newborn rats (n = 52) were randomly set to three groups: control (n = 18, sham operation), HIBD (n = 17), or HBO (n = 17). Pups in the HBO group were subjected to hyperbaric oxygen treatment with 2 atmosphaera absolutus, 5 x 30 min at a 24 h intervals since 48-72 h after the HIBD model. All the animals were tested for the spatial learning and memory ability in the Morris water maze from postnatal days 37 to 41. At day-42, rats were decapitated and the brains were analyzed for morphological and histological changes, including brain shapes and weights, survival neurons, percentage of AchE positive area and NOS positive neurons in hippocampal CA1 region.</p><p><b>RESULTS</b>Rats in HBO and HIBD groups displayed significant morphological and histological damages, as well as severe spatial learning and memory disability. The average escape latency of Morris water maze in HBO group [(56 +/- 23) s] and HIBD group [(56 +/- 22) s] were longer than the control [(23 +/- 16) s] (P < 0.05). The swimming time in HBO group [(30 +/- 5) s] and HIBD group [(29 +/- 6) s] were shorter than the control [(51 +/- 5) s] (P < 0.05). The swimming length in HBO group [(572 +/- 92) cm] and HIBD group [(548 +/- 92) cm] were shorter than the control [(989 +/- 101) cm] (P < 0.05). The weight of left brains in HBO group [(598 +/- 46) mg] and HIBD group [(601 +/- 59) mg] were lighter than the control [(984 +/- 18) mg] (P < 0.05). The survival neurons of hippocamal CA1 region in HBO group [(97 +/- 27)/mm] and HIBD group [(100 +/- 27)/mm] were less than the control [(183 +/- 8)/mm] (P < 0.05). The percentage of AchE-positive fibers in HBO group [(18.4 +/- 2.2)%] and HIBD group [(18.5 +/- 2.2)%] were less than the control [(27.5 +/- 2.2)%,] (P < 0.05). NOS-positive neurons in HBO group [(21 +/- 5)/mm(2)] and HIBD group [(19 +/- 4)/mm(2)] were also less than the control [(34 +/- 6)/mm(2)] (P < 0.05).</p><p><b>CONCLUSION</b>Delayed HBO therapy resulted in no protection against either HIBD-induced brain morphological and histological deficits or spatial learning and memory disability.</p>

Angiogenesis and its regulatory factors in brain tissue of neonatal rat hypoxic-ischemic encephalopathy / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate possible mechanism of angiogenesis in brain tissue of neonatal rat hypoxic-ischemic encephalopathy (HIE).</p><p><b>METHODS</b>Forty seven-day old neonatal rats were randomly assigned to hypoxic-ischemic (Model group) or sham treatment (Sham group), each group had 20 rats. Five rats from each group were sacrificed on days 1, 3, 7 and 14 after hypoxia-ischemia. Paraffin sections of the brain were stained with anti-endothelial cell, anti-proliferating cell nuclear antigen (PCNA) or anti-vascular endothelial growth factor (VEGF) by using single or double immunohistochemistry. The brain capillary density index (BCDI), brain proliferating capillary density index (BPCDI) and the expression of VEGF were analyzed under the microscope. The expression of VEGF and hypoxia-inducible factor-1alpha (HIF-1alpha) mRNA in hypoxic-ischemic side of the brain was measured by RT-PCR.</p><p><b>RESULTS</b>BCDI around infarct brain tissue in the model group began to rise on day 3 and remained higher than that of the sham group from day 3 to day 14 [day 3: (9.80 +/- 1.05)/HPF vs. (4.90 +/- 0.66)/HPF, P < 0.01;day 14: (13.29 +/- 3.90)/HPF vs. (6.08 +/- 1.50)/HPF, P < 0.01]. Occasional proliferating capillary was found in brain tissue of normal neonatal rats. The density of proliferating brain capillary on day 3 and day 7 of Model group [(0.54 +/- 0.15)/HPF vs. (0.90 +/- 0.25)/HPF] were significantly higher than those of Sham group [(0.12 +/- 0.05)/HPF vs. (0.13 +/- 0.07)/HPF, P < 0.01]. VEGF was mainly expressed in the cytoplasm of neurons, capillary endothelial cells and pial cells. Viable neurons and endothelial cells in the infarct areas also expressed VEGF. The expression of VEGF mRNA in hypoxic-ischemic brain tissue was significantly higher than that of normal control (P < 0.01) and temporally preceded angiogenesis. The expression of VEGF mRNA at 12 hours of HIE model was significantly higher than that of normal control (1.56 +/- 0.27 vs. 0.95 +/- 0.21, P < 0.05). It reached its peak on day 1 and day 3 (1.85 +/- 0.31 vs. 1.86 +/- 0.39), significantly higher than that of normal control (P < 0.01), and decreased by day 7 and day 14, without significant difference compared with normal control (P > 0.05). The expression of HIF-1alpha mRNA was also up-regulated after hypoxic-ischemic treatment. The expression of HIF-1alpha mRNA (1.07 +/- 0.21) was significantly higher than that of normal control (0.64 +/- 0.28, P = 0.048) at 3-hour of HIE model, reached its peak on day 1 (1.73 +/- 0.42, P < 0.01), remained at high expression level on day 3 (1.44 +/- 0.36, P < 0.05) and began to decline by day 7 and day 14 when it was not significantly different from normal control.</p><p><b>CONCLUSIONS</b>Angiogenesis exists in the brain tissue of neonatal rat HIE model. Up-regulation of VEGF expression mediated by HIF-1 may play an important role in the process of angiogenesis.</p>

Meconium Ileus Combined with Pseudohypoaldosteronism Type Ⅰ in 1 Child / 实用儿科临床杂志

Objective To improve the recognition of meconium ileus and pseudohypoaldosteronism type Ⅰ and to explore the relationship between neonatal meconium ileus and cystic fibrosis.Methods The clinical and follow-up data of a premature infant with meconium ileus and pseudohypoaldosteronism type Ⅰ was analyzed.Relevant literature was reviewed.Results The child was a very low-birth weight premature infant who didn′t pass meconuim within 24 hours of birth and persistent abdominal distention was noted.Laparotomy was performed on day 4.Thick and inspissated meconium was found in the ileum with perforation.The atretic intestine was resected,and a double-barreled enterostomies was performed.On day 30,the child presented hyponatremia,hyperkalemia,high levels of plasma renin and aldosterone and was given 9 g/L salt supplementation.At 6-month age,9 g/L salt supplementation was discontinued.Anastomosis was performed at 8-month age.The child recovered with a good prognosis whose catch-up growth was obtained at 18-month age and didn′t pre-sent manifestations of cystic fibrosis.Conclusions This case could be diagnosed as meconium ileus and pseudohypoaldosteronism type Ⅰ.The relationship between neonatal meconium ileus and cystic fibrosis is different in China and the regions of Caucasian.