Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network.

BACKGROUND: Vitamin A supplementation may reduce the risk of chronic lung disease and sepsis in extremely-low-birth-weight infants. The results of our pilot study suggested that a dose of 5000 IU administered intramuscularly three times per week for four weeks was more effective than the lower doses given in past trials. METHODS: We performed a multicenter, blinded, randomized trial to assess the effectiveness and safety of this regimen as compared with sham treatment in 807 infants in need of respiratory support 24 hours after birth. The mean birth weight was 770 g in the vitamin A group and 769 g in the control group, and the respective gestational ages were 26.8 and 26.7 weeks. RESULTS: By 36 weeks' postmenstrual age, 59 of the 405 infants (15 percent) in the vitamin A group and 55 of the 402 infants (14 percent) in the control group had died. The primary outcome - death or chronic lung disease at 36 weeks' postmenstrual age - occurred in significantly fewer infants in the vitamin A group than in the control group (55 percent vs. 62 percent; relative risk, 0.89; 95 percent confidence interval, 0.80 to 0.99). Overall, 1 additional infant survived without chronic lung disease for every 14 to 15 infants who received vitamin A supplements. The proportions of infants in the vitamin A group and the control group who had signs of potential vitamin A toxicity were similar. The proportion of infants with serum retinol values below 20 microg per deciliter (0.70 micromol per liter) was lower in the vitamin A group than in the control group (25 percent vs. 54 percent, P<0.001). CONCLUSIONS: Intramuscular administration of 5000 IU of vitamin A three times per week for four weeks reduced biochemical evidence of vitamin A deficiency and slightly decreased the risk of chronic lung disease in extremely-low-birth-weight infants.     

Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants.

BACKGROUND: The prophylactic administration of indomethacin reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants (those with birth weights below 1500 g). Whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in renal, intestinal, and cerebral blood flow is not known. METHODS: Soon after they were born, we randomly assigned 1202 infants with birth weights of 500 to 999 g (extremely low birth weight) to receive either indomethacin (0.1 mg per kilogram of body weight) or placebo intravenously once daily for three days. The primary outcome was a composite of death, cerebral palsy, cognitive delay, deafness, and blindness at a corrected age of 18 months. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly within the same time frame. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrhage, chronic lung disease, ultrasonographic evidence of intracranial abnormalities, necrotizing enterocolitis, and retinopathy. RESULTS: Of the 574 infants with data on the primary outcome who were assigned to prophylaxis with indomethacin, 271 (47 percent) died or survived with impairments, as compared with 261 of the 569 infants (46 percent) assigned to placebo (odds ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4; P=0.61). Indomethacin reduced the incidence of patent ductus arteriosus (24 percent vs. 50 percent in the placebo group; odds ratio, 0.3; P<0.001) and of severe periventricular and intraventricular hemorrhage (9 percent vs. 13 percent in the placebo group; odds ratio, 0.6; P=0.02). No other outcomes were altered by the prophylactic administration of indomethacin. CONCLUSIONS: In extremely-low-birth-weight infants, prophylaxis with indomethacin does not improve the rate of survival without neurosensory impairment at 18 months, despite the fact that it reduces the frequency of patent ductus arteriosus and severe periventricular and intraventricular hemorrhage.     

Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units

BACKGROUND: Bacterial vaginosis has been associated with preterm birth. In clinical trials, the treatment of bacterial vaginosis in pregnant women who previously had a preterm delivery reduced the risk of recurrence. METHODS: To determine whether treating women in a general obstetrical population who have asymptomatic bacterial vaginosis (as diagnosed on the basis of vaginal Gram's staining and pH) prevents preterm delivery, we randomly assigned 1953 women who were 16 to less than 24 weeks pregnant to receive two 2-g doses of metronidazole or placebo. The diagnostic studies were repeated and a second treatment was administered to all the women at 24 to less than 30 weeks' gestation. The primary outcome was the rate of delivery before 37 weeks' gestation. RESULTS: Bacterial vaginosis resolved in 657 of 845 women who had follow-up Gram's staining in the metronidazole group (77.8 percent) and 321 of 859 women in the placebo group (37.4 percent). Data on the time and characteristics of delivery were available for 953 women in the metronidazole group and 966 in the placebo group. Preterm delivery occurred in 116 women in the metronidazole group (12.2 percent) and 121 women in the placebo group (12.5 percent) (relative risk, 1.0; 95 percent confidence interval, 0.8 to 1.2). Treatment did not prevent preterm deliveries that resulted from spontaneous labor (5.1 percent in the metronidazole group vs. 5.7 percent in the placebo group) or spontaneous rupture of the membranes (4.2 percent vs. 3.7 percent), nor did it prevent delivery before 32 weeks (2.3 percent vs. 2.7 percent). Treatment with metronidazole did not reduce the occurrence of preterm labor, intraamniotic or postpartum infections, neonatal sepsis, or admission of the infant to the neonatal intensive care unit. CONCLUSIONS: The treatment of asymptomatic bacterial vaginosis in pregnant women does not reduce the occurrence of preterm delivery or other adverse perinatal outcomes.     

A randomized comparison of transcervical and transabdominal chorionic-villus sampling. The U.S. National Institute of Child Health and Human Development Chorionic-Villus Sampling and Amniocentesis Study Group.

BACKGROUND. Chorionic-villus sampling is done in early pregnancy to obtain fetal cells for the prenatal diagnosis of genetic and chromosomal defects. Transcervical chorionic-villus sampling has been shown to be safe and effective in national trials. Recently, an alternative transabdominal technique has been suggested as potentially easier and safer. METHODS. From April 1987 through September 1989, we prospectively compared transcervical and transabdominal chorionic-villus sampling in 3999 women with singleton pregnancies in whom the risk of a genetically abnormal fetus was increased. Women between 7 and 12 weeks of gestation underwent ultrasonographic evaluation of placental and uterine position. Those with active vaginal infections, active bleeding, or cervical polyps were excluded. If the obstetrician thought either sampling procedure was acceptable, the woman was asked to consent to random assignment to one of the two procedures. Both groups were followed to determine the outcome of pregnancy and the rate of spontaneous fetal loss after chorionic-villus sampling. RESULTS. Among the 3999 women who entered the study, sampling was attempted in 3873 (97 percent), 1944 of whom had been assigned to undergo transcervical sampling and 1929 to undergo transabdominal sampling. Of these 3873 women, sampling was eventually successful in 3863. Sampling was successful after a single insertion of the sampling instrument in 94 percent of the transabdominal procedures and 90 percent of the transcervical procedures. Among the women with cytogenetically normal pregnancies who had sampling because of maternal age, the rate of spontaneous fetal loss through 28 weeks of pregnancy was 2.5 percent in the transcervical-sampling group and 2.3 percent in the transabdominal-sampling group (difference, 0.26 percent; 95 percent confidence interval, -0.5 to 1.0 percent). CONCLUSIONS. Transabdominal and transcervical chorionic-villus sampling appear to be equally safe procedures for first-trimester diagnosis of fetal abnormalities.     

The absence of a relation between the periconceptional use of vitamins and neural-tube defects. National Institute of Child Health and Human Development Neural Tube Defects Study Group

Whether taking multivitamins or folate around the time of conception can reduce a woman's risk of having a child with a neural-tube defect is controversial. To investigate this question, we examined the periconceptional use of vitamin supplements by women who had a conceptus with a neural-tube defect (n = 571), women who had had a stillbirth or a conceptus with another malformation (n = 546), and women who had had a normal conceptus (n = 573). Women with conceptuses with neural-tube defects were identified either prenatally or postnatally and were matched to control mothers for gestational age. To minimize recall bias, we interviewed nearly all the women within five months of the diagnosis of a birth defect or the birth of the infant (mean, 84 days); information on vitamin use was obtained by an interviewer who was unaware of the outcome of pregnancy. The rate of periconceptional multivitamin use among the mothers of infants with neural-tube defects (15.8 percent) was not significantly different from the rate among mothers in either the abnormal or the normal control group (14.1 percent and 15.9 percent, respectively). After adjustment for potential confounding factors, the odds ratio for having an infant with a neural-tube defect among women classified as having had full supplementation with multivitamins was 0.95 as compared with the mothers of the abnormal infants (95 percent confidence interval, 0.78 to 1.14) and 1.00 as compared with the mothers of normal infants (95 percent confidence interval, 0.83 to 1.20). There were no differences among the groups in the use of folate supplements. The adjusted odds ratio for having an infant with a neural-tube defect among those receiving the recommended daily allowance of folate was 0.97 as compared with the mothers of abnormal infants (95 percent confidence interval, 0.79 to 1.18) and 0.98 as compared with the mothers of normal infants (95 percent confidence interval, 0.80 to 1.20). We conclude that the periconceptional use of multivitamins or folate-containing supplements by American women does not decrease the risk of having an infant with a neural-tube defect.     

The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis

BACKGROUND. In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease. METHODS. We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San José, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days. RESULTS. The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5). CONCLUSIONS. The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis.     

Institutional profile: National Institute of Neurological Disorders and Stroke and National Institute of Mental Health

The nervous system is consistently viewed as a target of high interest for stem cell-based therapeutics. In the USA, the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Mental Health (NIMH) are the two largest funders of neuroscience-related research within the NIH. Research spanning the spectrum of basic, translational and clinical science is conducted both on the NIH campus and through funding of extramural research organizations across the USA, and, to a lesser extent, worldwide. In this brief survey, we will present an overview of stem cell-related activities at the two neuroscience-focused NIH institutes.     

Integrating Human Immunodeficiency Virus and Reproductive,Maternal and Child,and Tuberculosis Health Services Within National Health Systems

Joint United Nations Programme on HIV/AIDS (UNAIDS) established 90–90–90 HIV treatment targets for 2020 including the following: 90 % of HIV-infected people know their HIV status, 90 % of HIV-infected people who know their status are on treatment, and 90 % of people on HIV treatment have a suppressed viral load. Integration of HIV and other programs into the national health system provides an important pathway to reach those targets. We examine the case for integrating HIV and other health services to ensure sustainability and improve health outcomes within national health systems. In this non-systematic review, we examined recent studies on integrating HIV, tuberculosis (TB), maternal-child health (MCH), and sexually transmitted infection (STI) programs. Existing evidence is limited about the effectiveness of integration of HIV and other services. Most studies found that service integration increased uptake of services, but evidence is mixed about the effect on health outcomes or quality of health services. More rigorous studies of different strategies to promote integration over a wider range of services and settings are needed. Research on how best to maximize benefits, including sustainability, of integrated services is necessary to help inform international and national policy. We recommend additional interventions to test how best to integrate HIV and MCH services, HIV and TB services, HIV testing and treatment, and STI testing and treatment.     

Health and Human Development: Understandings From Life-Course Research

It is now well understood that life-course factors affect a diverse range of outcomes, from general well-being to physical functioning and chronic diseases. Exposure to both beneficial and adverse circumstances over the life course will vary for each individual and will constitute a unique life exposure trajectory, which will manifest as different expressions of health and well-being. Here, we present a 3-fold model of life-course influences on health: latency, cumulative, and pathway. By latency we mean relationships between an exposure at one point in the life course and the probability of health expressions years or decades later, irrespective of intervening experience. Cumulative refers to multiple exposures over the life course whose effects on health combine. Finally, pathways represent dependent sequences of exposures in which exposure at 1 stage of the life course influences the probability of other exposures later in the life course, as well as associated expressions. Evidence demonstrating these relationships suggests that, without a consideration of early life as well as adult life experience, policies designed to improve health status tend to overlook root causes.     

Birthweight and paternal involvement predict early reproduction in British women: Evidence from the National Child Development Study

There is considerable interest in the mechanisms maintaining early reproduction in the most socioeconomically disadvantaged groups in developed countries. Previous research has suggested that differential exposure to early‐life factors such as low birthweight and lack of paternal involvement during childhood may be relevant. Here, we used longitudinal data on the female cohort members from the UK National Child Development Study (n = 3,014–4,482 depending upon variables analyzed) to investigate predictors of early reproduction. Our main outcome measures were having a child by age 20, and stating at age 16 an intended age of reproduction of 20 years or lower. Low paternal involvement during childhood was associated with increased likelihood of early reproduction (O.R. 1.79–2.25) and increased likelihood of early intended reproduction (O.R. 1.38–2.50). Low birthweight for gestational age also increased the odds of early reproduction (O.R. for each additional s.d. 0.88) and early intended reproduction (O.R. for each additional s.d. 0.81). Intended early reproduction strongly predicted actual early reproduction (O.R. 5.39, 95% CI 3.71–7.83). The results suggest that early‐life factors such as low birthweight for gestational age, and low paternal involvement during childhood, may affect women's reproductive development, leading to earlier target and achieved ages for reproduction. Differential exposure to these factors may be part of the reason that early fertility persists in socioeconomically disadvantaged groups. We discuss our results with respect to the kinds of interventions likely to affect the rate of teen pregnancy. Am. J. Hum. Biol., 2010. © 2009 Wiley‐Liss, Inc.     

Development of ultrasonic vocalization responses in genetically heterogeneous National Institute of Health (N:NIH) rats. II. Associations among variables and behaviors

In this study, the first three generations of laboratory-reared, 10-day-old pups of the N:NIH strain were examined for ultrasonic vocalizations (USV) rates in response to 2 min of isolation. The purpose of the study was to determine baseline USV rates in these progenitor (PR1, PR2, PR3) generations prior to selective breeding for high and low rates of USV. In addition, this study aimed to detect sources of variation in USV between and within generations and sexes, and factors associated with USV during isolation across the generations. Data were collected from 532 10 day-old pups in 81 litters. Evaluation by principal component analyses revealed four factors corresponding roughly to constructs indicative of: thermoregulation; maturity and exploratory behavior; distress/anxiety, in which USV consistently appeared; and activity. Different component structures for each sex suggested that USV may represent different dimensions of anxiety for the sexes, with some degree of overlap. Nonetheless, all variables measured during isolation testing accounted for only a small portion of the variance in individual pup USV (less than 9%) at 10 days of age, when the effects of intercorrelations among all variables were taken into account. This suggests that variables currently measured do not represent a comprehensive model for the control of USV. © 1996 John Wiley & Sons, Inc.     

从十年文献统计分析看我国儿童少年精神医学的发展

目的：通过文献分析儿童精神卫生专业的发展现状，为学科建设提供一些可供参考的信息。方法：采用手工结合计算机光盘检索的方法查阅国内７４种专业医学杂志的儿童少年精神卫生文献。结果：１０年共发表论著、论著摘要和病例分析８９６篇，病例报道１１０篇，文献数量逐年增加。著者主要来源于儿科学、精神病学、预防医学和心理学４个专业学科，并且主要集中在少数省市的科研机构、大专院校及其附属医院。研究内容以精神发育迟滞及智力问题为最多，其次为心理测量和行为障碍，情绪障碍、心身障碍、抽动性障碍以及人格问题的研究报道也有一定数量。研究方法主要为病例对照和描述性研究，研究对象的年龄涉及儿童青少年的各个阶段，以学龄期的文献最多。结论：我国儿童精神卫生专业的发展已经达到了一定的规模，但与发达国家相比仍存在很大的差距，建议利用我国现有的医疗保健资源，在精神病学和儿保系统的基础上加速儿童精神卫生专业的学科发展。     

Effects of early experience and dexamethasone on adrenocortical reactivity.

This investigation tested the hypothesis that changes in circulating adrenocortical hormones mediate the long term effects of shocking infant rats. Dexamethasone administered through the mothers' milk was used to block adrenocortical responses to peripheral shock stimulation by the young. Control experiments indicated that the dexamethasone was present in the pups as early as 2 days after the mothers began drinking water containing dexamethasone. Shock reduced adrenocortical reactivity under conditions where the mother and the young were capable of an adrenocortical response to the shock, where either the mother or the young could have a response, and where neither the mother nor the young could have an adrenocortical response to this early stimulation. These data do not support the hypothesis that a pituitary-adrenocortical response of either the mother or the young mediates the effects of stimulation in infancy on subsequent adrenocortical reactivity.     

儿童青少年心理健康量表的编制和信效度检验

目的:编制一个用于儿童和青少年的心理健康量表,检验其信度和效度。方法:用新编的心理健康量表测查全国12个省(市)9278名儿童或他们的父母和143名异常样本,间隔5周的重测样本有87人,父母和儿童报告一致性检验样本56人,效标效度样本30人。用相关分析和因素分析考查量表的信度和效度。结果:新编量表的重测信度为0·713,Crobachα系数为0·847,分半信度为0·800,评定者信度为0·874;正常儿童在量表上的得分显著高于异常样本的得分(F=63·34-238·8,P<0·01);新编量表总分及分量表与儿童行为量表(CBCL)得分有一定的正或负的相关(r=0·27~0·609,P<0·05或0·01);探索性因素分析和验证性因素分析结果显示因素模式与量表编制者的理论构想一致。结论:儿少心理健康量表具有较好的信度和效度,可以用于儿童和青少年的心理健康评估。