Death In Early Infancy Research Articles

Short QT syndrome: clinical findings and diagnostic-therapeutic implications

Clinical presentation, occurrence of sudden infant death, and results of the available therapies in the largest group of patients with short QT syndrome (SQTS), studied so far, are reported. Clinical history, physical examination, electrocardiogram (ECG), exercise stress testing, electrophysiological study, morphological evaluation, genetic analysis and therapy results in 29 patients with SQTS and personal and/or familial history of cardiac arrest are reported. The median age at diagnosis was 30 years (range 4-80). In all subjects, structural heart disease was excluded. Eighteen patients were symptomatic (62%): 10 had cardiac arrest (34%) and in 8 (28%) this was the first clinical presentation. Cardiac arrest had occurred in the first months of life in two patients. Seven patients had syncope (24%); 9 (31%) had palpitations with atrial fibrillation documented even in young subjects. At ECG, patients exhibited a QT interval < or = 320 ms and QTc < or = 340 ms. Fourteen patients received an implantable cardioverter-defibrillator (ICD) and 10 hydroquinidine prophylaxis. At a median follow-up of 23 months (range 9-49), one patient received an appropriate shock from the ICD; no patient on hydroquinidine had sudden death or syncope. SQTS carries a high risk of sudden death and may be a cause of death in early infancy. ICD is the first choice therapy; hydroquinidine may be proposed in children and in the patients who refuse the implant.

Air Pollution and Infant Death in Southern California, 1989–2000

We evaluated the influence of outdoor air pollution on infant death in the South Coast Air Basin of California, an area characterized by some of the worst air quality in the United States. Linking birth and death certificates for infants who died between 1989 and 2000, we identified all infant deaths, matched 10 living control subjects to each case subject, and assigned the nearest air monitoring station to each birth address. For all subjects, we calculated average carbon monoxide, nitrogen dioxide, ozone, and particulate matter < 10 microm in aerodynamic diameter exposures experienced during the 2-week, 1-month, 2-month, and 6-month periods before a case subject's death. The risk of respiratory death increased from 20% to 36% per 1-ppm increase in average carbon monoxide levels 2 weeks before death in early infancy (age: 28 days to 3 months). We also estimated 7% to 12% risk increases for respiratory deaths per 10-microg/m3 increase in particulate matter < 10 microm in aerodynamic diameter exposure experienced 2 weeks before death for infants 4 to 12 months of age. Risk of respiratory death more than doubled for infants 7 to 12 months of age who were exposed to high average levels of particulates in the previous 6 months. Furthermore, the risk of dying as a result of sudden infant death syndrome increased 15% to 19% per 1-part per hundred million increase in average nitrogen dioxide levels 2 months before death. Low birth weight and preterm infants seemed to be more susceptible to air pollution-related death resulting from these causes; however, we lacked statistical power to confirm this heterogeneity with formal testing. Our results add to the growing body of literature implicating air pollution in infant death from respiratory causes and sudden infant death syndrome and provide additional information for future risk assessment.

Pathologic and Molecular Analysis in a Family with Rare Mixed Supravalvar Aortic and Pulmonic Stenosis

Nonsyndromic supravalvar aortic stenosis (SVAS) is an obstructive vascular disorder often inherited in an autosomal dominant manner. With pulmonary artery involvement, stenotic lesions are nearly always peripheral or downstream of the pulmonic valve. In rare cases when the supravalvar pulmonic region is affected, the stenoses usually improve over time and rarely affect prognosis. We evaluated a unique family in which 10 of 14 individuals have nonsyndromic SVAS and 7 of the 10 affected family members with SVAS have the rare finding of supravalvar pulmonic stenosis (SVPS). In at least 2 of these individuals, the severity of SVPS was so significant that it led to death in early infancy. Pathologic examination of stenotic lesions in this kindred group revealed concentrically organized smooth muscle cells separated by dense elastic fibers. In contrast, the arterial pathology reported for other individuals with nonsyndromic SVAS demonstrates increased numbers of hypertrophied smooth muscle cells separated by thin, fragmented elastin fibers. Molecular analysis identified a novel ELN mutation within the donor splice site of exon 16, which may be responsible for the unique phenotype and distinct elastin histopathology found in this kindred.

RE: INSTRUCTIVE CASE: ‘DELAYED INFANT DEATH FOLLOWING CATASTROPHIC DETERIORATION DURING BREAST‐FEEDING’

25 May 2005 Dear Editor, Krous et al., in their Instructive Case entitled ‘Delayed infant death following catastrophic deterioration during breast-feeding’ (J. Paediatr. Child Health 2005; 41: 215–7) conclude that the sudden, unexpected deaths of two 6-weeks-old infants were due to the oronasal obstruction caused by breast-feeding. Blood noted in the nares of one, possibly both infants is given as the supporting evidence. How can the authors reliably link the activity of breast-feeding, while distracted, to these unexpected deaths and go on to conclude the cause to be oronasal obstruction? Neither event was accurately witnessed by mothers who were otherwise distracted, performing commonplace tasks during breast-feeding. Apnoea was noted in the first infant approximately 15 min after feeding activity had last been noted with no information available regarding the intervening period. The period of time while the second mother continued to shop before discovering her infant to be apnoeic is not known. There is no direct confirmation that the catastrophic deterioration occurred during the act of breast-feeding. Smothering has a recognized association with early infant death, yet these two cases provide insufficient data immediately before the events and have too many confounders to offer further insight. The peri and postprandial periods during early infancy constitute a significant proportion of the day and sudden infant death during these periods are to be expected. Feeding per se a small infant is a time of complex interaction with the environment with increased physical exertion and metabolic activity. It is a time when the frequency of adverse events might expect to increase. But to suggest, these two infants died as a direct result of inattention by the mother during breast-feeding, and entirely avoidable, is unsubstantiated.

De novocalcium/sulfur SAD phasing of the human formylglycine-generating enzyme using in-house data

Sulfatases are a family of enzymes essential for the degradation of sulfate esters. Formylglycine is the key catalytic residue in the active site of sulfatases and is generated from a cysteine residue by FGE, the formylglycine-generating enzyme. Inactivity of FGE owing to inherited mutations in the FGE gene results in multiple sulfatase deficiency (MSD), which leads to early death in infants. Human FGE was crystallized in the presence of traces of the protease elastase, which was absolutely essential for crystal growth, and the structure of FGE was determined by molecular replacement. Before this model was completed, the FGE structure was re-determined by SAD phasing using in-house data based on the anomalous signal of two calcium ions bound to the native enzyme and intrinsic S atoms. A 14-atom substructure was determined at 1.8 A resolution by SHELXD; SHELXE was used for density modification and phase extension to 1.54 A resolution. Automated model building with ARP/wARP and refinement with REFMAC5 yielded a virtually complete model without manual intervention. The minimal data requirements for successful phasing and the relative contributions of the Ca and S atoms are discussed and compared with the related FGE paralogue, pFGE. This work emphasizes the usefulness of de novo phasing using weak anomalous scatterers and in-house data.

Effect of indomethacin on complications of preterm neonatal respiratory distress syndrome after pulmonary surfactant treatment or prevention

目的 探讨预防性应用吲哚美辛减少肺表面活性物质治疗或预防新生儿呼吸窘迫综合征的合并症.方法临床诊断为新生儿呼吸窘迫综合征的早产儿40例,用肺表面活性物质(固尔苏)治疗,按有无用吲哚美辛预防分为A1组22例与B1组18例.胎龄＜32周未发生新生儿呼吸窘迫综合征的早产儿37例,用肺表面活性物质预防,按有无用吲哚美辛预防分为A2组24例与B2组13例.分别比较A1与B1组、A2与B2组的辅助通气(含鼻塞CPAP和机械通气)时间和发生动脉导管未闭、肺出血、脑室内出血及死亡情况分布并做统计学分析.结果A1与B1两组辅助通气时间分别为(94.9±61.5)h、(105.8±103.0)h,差异无统计学意义(P＞0.05);发生动脉导管未闭例数分别为8、14例,差异有统计学意义(P＜0.05);发生肺出血、脑室内出血例数的差异无统计学意义(P＞0.05);死亡例数≤3 d分别为0和3例,差异有统计学意义(P＜0.05),＞3 d各为3例,差异无统计学意义(P＞0.05).A2与B2两组辅助通气时间分别为(24.0±20.8)h、(44.0±25.9)h,发生动脉导管未闭例数分别为2和5例,差异均有统计学意义(P＜0.05);发生肺出血例数的差异无统计学意义(P＞0.05);发生脑室内出血例数较少,死亡例数≤3 d分别为0和1例,＞3 d各为1例,未做统计学分析.结论肺表面活性物质治疗或预防新生儿呼吸窘迫综合征时,用吲哚美辛预防可减少合并动脉导管未闭、肺出血和早期死亡。

Safety and efficacy of recombinant acid alpha-glucosidase (rhGAA) in patients with classical infantile Pompe disease: results of a phase II clinical trial

Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. Due to virtual absence of acid alpha-glucosidase, patients with classical infantile Pompe disease develop progressive cardiomyopathy, skeletal muscle weakness and respiratory insufficiency leading to death in early infancy. We report on the results of a phase II clinical trial including two patients with classical infantile Pompe disease receiving enzyme replacement therapy over a period of 48 weeks by weekly infusions. Recombinant acid alpha-glucosidase was derived from the milk of transgenic rabbits. Safety was evaluated by recording adverse events while clinical efficacy was evaluated by ventilator-free survival, left ventricular mass index, motor development as well as histologic and biochemical analysis of muscle biopsies. This therapy was in general well-tolerated. There was an overall improvement in left ventricular mass, cardiac function, skeletal muscle function and histological appearance of skeletal muscle.

Perinatal Mortality in West Germany Following Atmospheric Nuclear Weapons Tests

Using trend analysis, the author sought a possible association between perinatal mortality rates in West Germany, 1955-1993, and the fallout from atmospheric nuclear weapons testing in the years 1952-1993. The regression model used a continuously falling trend and a superimposed extra term that reflects the average strontium content in pregnant women. Mortality rates show an upward deviation that peaked in 1970. The model attributes more than 100,000 excess perinatal deaths to strontium in the fallout. The dose-response curve is curvilinear with a power of dose of 1.81 +/- 0.23. In addition, using a combined regression model, the author analyzed the two data subsets of perinatal mortality (i.e., stillbirth rate and early neonatal mortality). The strontium effect is 3.4 times greater on early infant deaths than on stillbirths. According to the prevailing wisdom, the fetus is protected against damage from ionizing radiation by a threshold dose of 50-200 mSv, but the doses from strontium in the fallout were well below 1 mSv/yr in Germany. The results reported here seem to contradict the existence of a threshold dose for perinatal mortality at low doses.

Unexpected clinical course in a 9-year-old boy with congenital hypomyelinating neuropathy due to a novel MPZ gene mutation

Objective: To introduce the unexpected clinical course of congenital hypomyelinating neuropathy (CHN) in a boy. Autosomal dominant/recessive CHN manifests usually in the neonatal period, possibly until the second year of life with generalized muscle weakness, -hypotonia, absent tendon reflexes, often complicated by feeding problems and respiratory difficulties. Prognosis is severe leading to death in early infancy; only a few cases are reported with longer survival.

Congenital Disorder of Glycosylation Type Ik (CDG-Ik): A Defect of Mannosyltransferase I

This study describes the discovery of a new inherited disorder of glycosylation named "CDG-Ik." CDG-Ik (congenital disorder of glycoslyation type Ik) is based on a defect of human mannosyltransferase I (MT-I [MIM 605907]), an enzyme necessary for the elongation of dolichol-linked chitobiose during N-glycan biosynthesis. Mutations in semiconserved regions in the corresponding gene, HMT-1 (yeast homologue, Alg1), in two patients caused drastically reduced enzyme activity, leading to a severe disease with death in early infancy. One patient had a homozygous point mutation (c.773C-->T, S258L), whereas the other patient was compound heterozygous for the mutations c.773C-->T and c.1025A-->C (E342P). Glycosylation and growth of Alg1-deficient PRY56 yeast cells, showing a temperature-sensitive phenotype, could be restored by the human wild-type allele, whereas only slight restoration was observed after transformation with the patients' alleles.

Effect of maternal HIV and malaria infection on pregnancy and perinatal outcome in Zimbabwe.

To investigate the effect of isolated or concomitant infection with malaria and HIV on pregnancy and neonatal outcome. Data were collected on pregnant women admitted during the rainy seasons in the obstetric division of a district referral hospital in northern Zimbabwe in 2000 and 2001. The effects of malaria and HIV infection were determined by multivariate analysis. The prevalence of HIV seropositivity and symptomatic malaria in 986 pregnant women was 8.3% and 14.7%, respectively. HIV-infected women were more likely to develop malaria attacks during pregnancy than seronegative women (odds ratio [OR] = 3.96, 95% confidence interval (CI): 2.42-6.46). Malaria and HIV infections were associated with increased risk of stillbirth (OR = 4.74, 95% CI: 1.34-16.78) and preterm delivery (OR = 4.10, 95% CI: 2.17-7.75), respectively. They were independently associated with increased risk of low birth weight (malaria: OR = 10.09, 95% CI: 6.50-15.65; HIV: OR = 3.16, 95% CI: 1.80-5.54) and very low birth weight (malaria: OR = 5.04, 95% CI: 1.00-25.43; HIV: OR = 10.74, 95% CI: 2.12-54.41), low Apgar score (malaria: OR = 4.45, 95% CI: 1.42-13.94; HIV: OR = 5.94, 95% CI: 1.66-21.30), and fetal growth restriction (malaria: OR = 3.98, 95% CI: 2.51-6.30; HIV: OR = 4.07, 95% CI: 2.40-6.92). Dual infection with malaria and HIV was associated with increased risk of maternal, perinatal, and early infant death. Women with single HIV or malaria infection have a significantly increased risk of adverse outcomes of pregnancy and childbirth. Dual infection has additional detrimental effects on maternal and infant survival in an area where HIV and malaria coexist.

Genes and male infertility: what can go wrong?

Genes and male infertility: what can go wrong?

Neurodevelopmental outcome of premature infants after antenatal phenobarbital exposure

Objective: We previously demonstrated that antenatal phenobarbital does not decrease the risk of intracranial hemorrhage or early death in premature infants. The objective of the present study was to evaluate the impact of antenatal phenobarbital exposure on the neurodevelopmental outcome of premature infants born to women who were participating in the randomized clinical trial of antenatal phenobarbital exposure. Study Design: Infants were evaluated at 18 to 22 months corrected age with a standard neurologic examination and the Bayley scales of infant development measuring the mental developmental index and the psychomotor developmental index. Results: Of the 578 infants <34 weeks of gestational age who were born to women who were enrolled in the primary study, 7 infants died after discharge from the neonatal intensive care unit, and 135 infants were lost to follow-up. Infants who were lost to follow-up had a higher mean birth weight and gestational age and a lower maternal education, but the rates of intracranial hemorrhage were comparable to those infants who were evaluated. Among the infants who were evaluated (n = 436; 76%), the mean birth weight and gestational age, maternal education, and frequency and distribution of intracranial hemorrhage were similar in the antenatal phenobarbital exposed and placebo groups. Eighteen infants (8%) in the antenatal phenobarbital exposed group and 21 infants (11%) in the placebo group had cerebral palsy (P = not significant). There was no difference between the 2 groups in either the median Bayley II mental developmental index (85 in the antenatal phenobarbital and 86 in the placebo group) or the Psychomotor Developmental Index (91 in the antenatal phenobarbital and 91 in the placebo group). Infants with intracranial hemorrhage (23%) had significantly lower mental developmental index and psychomotor developmental index scores than infants with no intracranial hemorrhage, independent of antenatal phenobarbital exposure. In the total cohort of 436 infants, the presence of intracranial hemorrhage or periventricular leukomalacia was associated with lower mental developmental index and psychomotor developmental index scores; the presence of increasing birth weight, maternal education, and a complete course of antenatal steroids was associated with a higher mental developmental index score. Conclusion: Antenatal phenobarbital exposure did not favorably or adversely affect the neurodevelopmental outcome of premature infants at 18 to 22 months of age. (Am J Obstet Gynecol 2002;187:171-7.)

Association of Maternal Fever During Labor With Neonatal and Infant Morbidity and Mortality

In Brief OBJECTIVE To examine the association of intrapartum fever with infant morbidity and early neonatal (0–6 days) and infant (0–364 days) death. METHODS We carried out a retrospective cohort analysis among singleton live births in the United States for the period 1995–1997 using the National Center for Health Statistics linked birth-infant death cohort data. RESULTS Among the 11,246,042 singleton live births during the study period, intrapartum fever (at least 38C) was recorded in 1.6%. Intrapartum fever was associated with early neonatal (adjusted odds ratio [OR], 95% confidence interval [CI] for preterm and term infants respectively: 1.32; 1.11, 1.56 and 1.67; 1.14, 2.46) and infant (OR, 95% CI for preterm and term, respectively: 1.31; 1.14, 1.51 and 1.27; 1.01, 1.59) death among nulliparous mothers. Among preterm infants of parous mothers, intrapartum fever was associated with early neonatal (OR 1.29, 95% CI 1.01, 1.64) death. In the combined analyses (infants of nulliparous and parous mothers), intrapartum fever was a strong predictor of infection-related death. These associations were stronger among term (OR 3.16, 95% CI 1.56, 6.40 for early neonatal; OR 1.75, 95% CI 1.20, 2.57 for infant death) than preterm infants (OR 1.52, 95% CI 1.15, 2.00 for early neonatal; OR 1.29, 95% CI 1.05, 1.57 for infant death). Intrapartum fever was also a risk factor for meconium aspiration syndrome, hyaline membrane disease, neonatal seizures, and assisted ventilation. CONCLUSION Intrapartum fever is an important predictor of neonatal morbidity and infection-related mortality. Maternal fever during labor is associated with infection-related neonatal and infant death.

Association of maternal fever during labor with neonatal and infant morbidity and mortality

Objective: To examine the association of intrapartum fever with infant morbidity and early neonatal (0–6 days) and infant (0–364 days) death. Methods: We carried out a retrospective cohort analysis among singleton live births in the United States for the period 1995–1997 using the National Center for Health Statistics linked birth-infant death cohort data. Results: Among the 11,246,042 singleton live births during the study period, intrapartum fever (at least 38C) was recorded in 1.6%. Intrapartum fever was associated with early neonatal (adjusted odds ratio [OR], 95% confidence interval [CI] for preterm and term infants respectively: 1.32; 1.11, 1.56 and 1.67; 1.14, 2.46) and infant (OR, 95% CI for preterm and term, respectively: 1.31; 1.14, 1.51 and 1.27; 1.01, 1.59) death among nulliparous mothers. Among preterm infants of parous mothers, intrapartum fever was associated with early neonatal (OR 1.29, 95% CI 1.01, 1.64) death. In the combined analyses (infants of nulliparous and parous mothers), intrapartum fever was a strong predictor of infection-related death. These associations were stronger among term (OR 3.16, 95% CI 1.56, 6.40 for early neonatal; OR 1.75, 95% CI 1.20, 2.57 for infant death) than preterm infants (OR 1.52, 95% CI 1.15, 2.00 for early neonatal; OR 1.29, 95% CI 1.05, 1.57 for infant death). Intrapartum fever was also a risk factor for meconium aspiration syndrome, hyaline membrane disease, neonatal seizures, and assisted ventilation. Conclusion: Intrapartum fever is an important predictor of neonatal morbidity and infection-related mortality.

Effect of labor on infant morbidity and mortality with preterm premature rupture of membranes: United States population- based study

Objective: To evaluate whether labor, in the setting of premature rupture of membranes (PROM), affects infant morbidity and mortality rates. Methods: We derived data for this population-based cohort study from the United States national linked birth infant death data sets, comprised of singleton live births delivered between 1995 and 1997. We included women ( n = 34,594) who had preterm PROM more than 12 hours and delivered between 23 and 32 weeks’ gestation. Birth records were used to determine whether delivery occurred with or without labor. Infants with birth weights below the tenth percentile for gestational age were classified as small for gestational age (SGA) on the basis of a nomogram of all singleton births in the United States between 1995 and 1997. Primary outcomes were early neonatal (0–6 days), late neonatal (7–27 days), postneonatal (28–365 days), and infant death (0–365 days). Secondary outcomes included respiratory distress syndrome (RDS), assisted ventilation, and neonatal seizures. Risks of infant mortality and morbidity from labor were examined separately for SGA and non-SGA infants. Results: Overall rates were infant death 11.6%, RDS 15.1%, assisted ventilation 25.9%, and neonatal seizure 0.2%. Labor was associated with higher incidence of early neonatal death in SGA infants (adjusted relative risk [RR] 1.24, 95% confidence interval [CI] 1.11, 1.38) but had no effect on other outcomes. Among non-SGA infants, labor had no effect on infant death but was associated with higher rates of RDS (RR 1.15, 95% CI 1.08, 1.22) and assisted ventilation (RR 1.16, 95% CI 1.08, 1.24). Conclusion: Although labor was associated with a slightly higher mortality rate in SGA infants and slightly more respiratory morbidity in non-SGA infants, recommendations regarding clinical treatment should await future clinical trials.

Osteopetrosis: a single centre experience of stem cell tranisplantation and prenatal diagnosis.

Malignant osteopetrosis (MOP) is an autosomal recessive disease in which osteoclast dysfunction results in excessive bone deposition and early infant death. Thirteen children suffering from MOP from four related families all belonging to one Bedouin tribe, were studied. The disease was diagnosed as early as at a few days postnatal to 5 months. Nine children underwent BMT, four of whom are still alive; one is blind and two have markedly reduced vision. Four children who did not undergo BMT died between 4 and 6 months of age. Recently, the gene for MOP has been mapped for this Bedouin tribe allowing prenatal diagnosis. Seven pregnancies were subsequently prenatally diagnosed and two fetuses were found to be affected. Pregnancy was electively terminated in one case. In the other case the parents refused and after establishing the diagnosis, the newborn was transplanted at the age of 7 days.

‘He was a Real Baby with Baby Things’

This article explores the ways members of pregnancy loss support groups in the US use material culture to deal with the ‘realness problem’ of miscarriage, stillbirth, and early infant death. I examine goods purchased or made for the child-to-be during pregnancy; goods given from the child-to-be during the pregnancy; goods given to, or in the memory of, the ‘baby’ after its death; and things acquired to memorialize the child within the family. Through the buying, giving, and preserving of things, women and their social networks actively construct their babies-to-be and would-have-been babies as ‘real babies’ and themselves as ‘real mothers’, worthy of the social recognition this role entails.

Failure to exclusively breastfeed and the risk of early infant mortality due to infectious disease in poor communities in Lima, Peru.

This case-control study was conducted to determine the relationship between feeding practices (and living conditions) and the risk of early infant mortality in a poor urban population in Lima Peru. Using the Epi-info 6.4 software a total of 236 records of dead infants due to infectious diseases were reviewed and only 135 were analyzed. Overall this study showed that failure to breast-feed (especially when not exclusively) during the first months and the living conditions of poor single-parent mothers greatly increase the risk of infant mortality due to infectious diseases. For both case and control groups the introduction of liquid supplements was a common practice but for infants who died the practice started much earlier. Results of this study support the view that current infant feeding practices remain an important cause of early infant deaths among poor urban families.

Life history and demography of wild moor macaques (Macaca maurus): Summary of ten years of observations

Data on the life history and demography of individual species are indispensable when we discuss social behavior from an evolutionary perspective, and when we attempt to make adequate conservation plans. This is the first report on the life history and demography of moor macaques in their natural habitat. Moor macaques (Macaca maurus) in the Karaenta Nature Reserve, South Sulawesi, Indonesia, have been observed since 1981. Individual identification of group members began in 1988. The size of the study group increased continuously, from 20 to 43, over this 10-year period of observation (1988–1998). The average population growth rate was 8.0%, and 45 births were confirmed during this period. They were categorized as moderately seasonal breeders. Mortality rate within one year after birth was 17.1%. Average inter-birth interval following surviving infants was 24.1 months, while that following early infant death was 15.0 months. As is the case in other species of macaques, males moved between groups while females stayed in their natal groups. Females seemed to exhibit their first perineal swelling at 4–6 years of age, and to have their first infant at 6–7 years. Males left their natal group at 7–9 years. Solitary males were seldom observed around the study group. The late dispersal of males from their natal groups and their infrequent movement between groups contrast with patterns in well-known macaque species such as Japanese macaques. Recently, differences in social characteristics among macaque species have attracted the attention of researchers. Our findings would be useful to further understanding of such social differences. Am. J. Primatol. 52:1–11, 2000. © 2000 Wiley-Liss, Inc.