Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: a role for gut microbiota?

Many epidemiological studies have shown the beneficial effects of a largely plant-based diet, and the strong association between the consumption of a Mediterranean-type diet with healthy aging including a lower risk of cognitive decline. The Mediterranean diet is characterized by a high intake of olive oil, fruits and vegetables and is rich in dietary fiber and polyphenols - both of which have been postulated to act as important mediators of these benefits. Polyphenols are large molecules produced by plants to protect them from environmental threats and injury. When ingested by humans, as little as 5% of these molecules are absorbed in the small intestine with the majority metabolized by the gut microbiota into absorbable simple phenolic compounds. Flavan-3-ols, a type of flavonoid, contained in grapes, berries, pome fruits, tea, and cocoa have been associated with many beneficial effects on several risk factors for cardiovascular disease, cognitive function and brain regions involved in memory formation. Both preclinical and clinical studies suggest that these brain and heart benefits can be attributed to endothelial vascular effects and anti-inflammatory properties among others. More recently the gut microbiota has emerged as a potential modulator of the aging brain and intriguingly polyphenols have been shown to alter microbiota composition and be metabolized by different microbial species. However, there is a need for well controlled studies in large populations to identify predictors of response, particularly given the vast inter-individual variation of human gut microbiota.

Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders.

There is emerging evidence that diet has a major modulatory influence on brain-gut-microbiome (BGM) interactions with important implications for brain health, and for several brain disorders. The BGM system is made up of neuroendocrine, neural, and immune communication channels which establish a network of bidirectional interactions between the brain, the gut and its microbiome. Diet not only plays a crucial role in shaping the gut microbiome, but it can modulate structure and function of the brain through these communication channels. In this review, we summarize the evidence available from preclinical and clinical studies on the influence of dietary habits and interventions on a selected group of psychiatric and neurologic disorders including depression, cognitive decline, Parkinson's disease, autism spectrum disorder and epilepsy. We will particularly address the role of diet-induced microbiome changes which have been implicated in these effects, and some of which are shared between different brain disorders. While the majority of these findings have been demonstrated in preclinical and in cross-sectional, epidemiological studies, to date there is insufficient evidence from mechanistic human studies to make conclusions about causality between a specific diet and microbially mediated brain function. Many of the dietary benefits on microbiome and brain health have been attributed to anti-inflammatory effects mediated by the microbial metabolites of dietary fiber and polyphenols. The new attention given to dietary factors in brain disorders has the potential to improve treatment outcomes with currently available pharmacological and non-pharmacological therapies.

Stillbirth: Genome-wide copy number variation profiling in archived placental umbilical cord samples with pathologic and clinical correlation.

INTRODUCTION: Stillbirth remains a devastating health issue with 26,000 stillbirths occurring annually in the United States. Formalin-fixed, paraffin-embedded (FFPE) umbilical cord samples are available for many stillbirths. Our aim was to validate the use of these samples in identifying genetic variations in stillbirth through microarray analysis. METHODS: This is a retrospective case-control study from a single institution of stillbirths ≥ 23 weeks gestational age and control liveborn infants. Fetal genomic DNA was extracted from FFPE umbilical cord samples of stillborn and control placentas, and genotyping was performed using the Illumina HumanOmniExpresss-12v1 Beadchip. Array results were verified with qPCR. RESULTS: 31 case-specific CNVs (17 deletions and 14 amplifications) with an average size of 294 kb for amplifications and 74 kb for deletions were identified among 94 FFPE samples (86 cases; 8 controls). In total 38 (44%) of the stillbirth samples had a CNV detected. Validation of a subset of microarray findings with qPCR confirmed deletions on 1p (2 cases), 11q (4 cases) and amplifications on 18 (1 case). Placental underperfusion changes were seen in stillborns with deletions on 1p, a region containing complement regulatory genes which have been shown to play a role in preeclampsia. DISCUSSION: This study validated the use of archived FFPE umbilical cord samples for genome-wide copy number profiling in stillbirths, and demonstrates specific CNV deletions and amplifications. Microarray analysis in an expanded cohort of stillbirth FFPE samples has the potential to identify biomarkers involved in stillbirth pathogenesis.

Usefulness of post mortem determination of serum tryptase, histamine and diamine oxidase in the diagnosis of fatal anaphylaxis.

The diagnosis of fatal anaphylaxis can be difficult for clinical features may not always be evident in necropsy. Therefore post mortem determination of tryptase and other blood parameters can be helpful in verifying the diagnosis. We compared post mortem tryptase, histamine and diamine oxidase (DAO) serum levels of two patients who had died after a Hymenoptera sting and one patient who died of bronchospasm during anaesthesia with data obtained from 55 control subjects who had died from other causes than anaphylaxis. In the three anaphylactic cases, serum tryptase level was 880, 68 and 200 µg/l (normal range in living subjects: <11.4 µg/l), histamine was 37.5, 8.5 and 23.2 ng/ml (normal range: <0.3 ng/ml) and DAO was 1, 30 and 4 U/ml (normal range 10-30 U/ml), respectively. Values in the control group were as follows: tryptase 1-340 µg/l (mean 24.2 ± 58.2), histamine 5.0-22.0 ng/ml (mean 14.7 ± 3.9) and DAO 0-114 U/ml (mean 21.1 ± 27.8). 19/55 (34.5%) of the controls had elevated tryptase levels >11.4 µg/l, with four of them showing values >45 µg/ml. Significantly higher histamine levels were seen in blood samples taken more than 24h post mortem (p<0.05), whereas the timing of blood collection had no effect on tryptase and DAO levels. While moderately elevated tryptase levels are common in post mortem sera, values above 45 µg/l may support the diagnosis of fatal anaphylaxis. Strongly elevated histamine levels might give an additional clue on fatal anaphylaxis, whereas DAO does not seem to be helpful.

[Jellyfish and poison-producing animals that endanger swimmers]. / Quallen und Gifttiere als Gefahr beim Baden.

Exposure to fresh water as well as to sea water can cause unpleasant consequences. The water of lakes or biotopes may be the reason for severe itching reactions on exposed skin, caused by cercariae. Exposure to seawater may lead to skin affections including itching or burning urticarial lesions as well as life threatening reactions. The causes for these reactions are especially species of jellyfish.

Cardiopulmonary monitoring at home: the CHIME monitor.

A new physiologic monitor for use in the home has been developed and used for the Collaborative Home Infant Monitor Evaluation (CHIME). This monitor measures infant breathing by respiratory inductance plethysmography and transthoracic impedance; infant electrocardiogram, heart rate and R-R interval; haemoglobin O2 saturation of arterial blood at the periphery and sleep position. Monitor signals from a representative sample of 24 subjects from the CHIME database were of sufficient quality to be clinically interpreted 91.7% of the time for the respiratory inductance plethysmograph, 100% for the ECG, 99.7% for the heart rate and 87% for the 16 subjects of the 24 who used the pulse oximeter. The monitor detected breaths with a sensitivity of 96% and a specificity of 65% compared to human scorers. It detected all clinically significant bradycardias but identified an additional 737 events where a human scorer did not detect bradycardia. The monitor was considered to be superior to conventional monitors and, therefore, suitable for the successful conduct of the CHIME study.

Cardiorespiratory events recorded on home monitors: Comparison of healthy infants with those at increased risk for SIDS.

CONTEXT: Home monitors designed to identify cardiorespiratory events are frequently used in infants at increased risk for sudden infant death syndrome (SIDS), but the efficacy of such devices for this use is unproven. OBJECTIVE: To test the hypothesis that preterm infants, siblings of infants who died of SIDS, and infants who have experienced an idiopathic, apparent life-threatening event have a greater risk of cardiorespiratory events than healthy term infants. DESIGN: Longitudinal cohort study conducted from May 1994 through February 1998. SETTING: Five metropolitan medical centers in the United States. PARTICIPANTS: A total of 1079 infants (classified as healthy term infants and 6 groups of those at risk for SIDS) who, during the first 6 months after birth, were observed with home cardiorespiratory monitors using respiratory inductance plethysmography to detect apnea and obstructed breathing. MAIN OUTCOME MEASURES: Occurrence of cardiorespiratory events that exceeded predefined conventional and extreme thresholds as recorded by the monitors. RESULTS: During 718 358 hours of home monitoring, 6993 events exceeding conventional alarm thresholds occurred in 445 infants (41%). Of these, 653 were extreme events in 116 infants (10%), and of those events with apnea, 70% included at least 3 obstructed breaths. The frequency of at least 1 extreme event was similar in term infants in all groups, but preterm infants were at increased risk of extreme events until 43 weeks' postconceptional age. CONCLUSIONS: In this study, conventional events are quite common, even in healthy term infants. Extreme events were common only in preterm infants, and their timing suggests that they are not likely to be immediate precursors to SIDS. The high frequency of obstructed breathing in study participants would likely preclude detection of many events by conventional techniques. These data should be important for designing future monitors and determining if an infant is likely to be at risk for a cardiorespiratory event.

Genetic segregation analysis of autonomic nervous system dysfunction in families of probands with idiopathic congenital central hypoventilation syndrome.

Idiopathic congenital central hypoventilation syndrome (CCHS) is a very rare syndrome with major respiratory complications. Hypothesizing that CCHS is the most severe manifestation of general autonomic nervous system dysfunction (ANSD), we applied a case-control family study design to investigate the genetics of ANSD. Fifty-two probands with CCHS were identified, as well as 52 age-, race-, and gender-matched controls. ANSD phenotypic features were characterized in the cases, controls, and their family members. Our earlier studies found that most ANSD symptoms were more likely in CCHS cases and their relatives than in controls and their relatives (P < 0.05). The goal of the current study was to determine if the familiality of ANSD was consistent with a genetic pattern. We performed major locus segregation analysis of ANSD utilizing regressive models. CCHS probands were assumed to be affected; controls and relatives were designated as affected if they had two or more relevant symptoms. The hypothesis of "no transmission and no familial effects" was rejected in both case and control families. Case families were consistent with transmission of a major effect; control families were not (the difference in the pattern of results was significant, P < 0.0001). In the total data set, the best-fitting model was codominant Mendelian inheritance of a major gene for ANSD. These case-control family studies support our hypothesis that CCHS is the most severe manifestation of a general ANSD, with a family pattern consistent with Mendelian transmission, and demonstrate the potential utility of the approach to studies of other, similarly intractable disorders.

Case/control family study of autonomic nervous system dysfunction in idiopathic congenital central hypoventilation syndrome.

Children with idiopathic congenital central hypoventilation syndrome (CCHS) have a complex phenotype consistent with an imbalance of the autonomic nervous system (ANS). Since CCHS may be genetic in origin, we hypothesized that relatives of individuals with CCHS may exhibit symptoms of ANS dysfunction (ANSD), albeit in a milder form. We tested this hypothesis by assessing aspects of ANS function in relatives of CCHS cases vs. relatives of matched controls with a scripted questionnaire. Only those 35 symptoms of ANSD exhibited by > or =5% of the CCHS cases were included in the analysis as the basis for determining ANSD affection status. Two different arbitrary ANSD affection status definitions are presented in detail: any case, control, or relative with positive findings (1) in two or more symptoms, or (2) in two or more systems. The subjects included in the analysis totaled 2,353, including 56 CCHS cases, 56 age-, gender-, and race-matched controls, and their families. Under each of the two arbitrary ANSD affection statuses, CCHS cases and parents of cases were more likely to be affected than controls and parents of controls (P < 0.001 for both comparisons), 16% of the CCHS siblings had the ANSD phenotype with two or more symptoms, compared to 4% of control siblings (P = 0.03). Aunts and uncles of the CCHS cases were also significantly more likely to have two or more ANSD symptoms than were aunts and uncles of the controls (P= 0.009). These results support our hypothesis and also indicate that relatives of the CCHS cases tended to manifest a milder spectrum of ANSD, with fewer systems and/or fewer symptoms than the cases.

Comparison of apnea identified by respiratory inductance plethysmography with that detected by end-tidal CO(2) or thermistor. The CHIME Study Group.

As part of the Collaborative Home Infant Monitoring Evaluation (CHIME) we compared apnea identified by a customized home monitor using respiratory inductance plethysmography (RIP) with simultaneously recorded polysomnography-acquired nasal end-tidal CO(2) (PET(CO(2))) and nasal/oral thermistor in 422 infants during overnight laboratory recordings to determine concordance between techniques, sources of disagreement, and capacity of RIP to detect obstructed breaths within an apnea. Among 233 episodes of apnea identified by at least one method as >/= 16 s, 120 were observed by the CHIME monitor, 219 by PET(CO(2)), and 163 by thermistor. The positive predictive value of the CHIME-identified apnea was 89.2% (95% CI 83, 95) and 73% (95% CI 65, 81) for PET(CO(2)) and thermistor, respectively. However, the sensitivity of the CHIME monitor in identifying events detected by the other methods was only approximately 50%. Among 87 apnea events identified by all three techniques, no two methods showed high agreement in measurement of apnea duration: RIP and PET(CO(2)) (ICC = 0.54), RIP and thermistor (ICC = 0.13), PET(CO(2)) and nasal thermistor (ICC = 0.41). Among the 179 breaths identified by RIP as obstructed, 79.9% were judged to be obstructed on the PET(CO(2)) and 80.4% were judged to be obstructed on the thermistor channel. Among 238 breaths identified on PET(CO(2)) as obstructed, 54.2% were determined to be obstructed by RIP. Among 204 breaths identified on thermistor as obstructed, 55. 4% were determined to be obstructed by RIP. Reasons for discrepancies in apnea detection among channels included body movement, partial airway obstruction, and obstructed breaths. Despite these limitations the CHIME monitor provides an opportunity to record physiological data previously unavailable in the home.

Cardiac rhythm disturbances among children with idiopathic congenital central hypoventilation syndrome.

The objective of this study was to determine whether subjects with congenital central hypoventilation syndrome (CCHS) had an increased frequency of cardiac arrhythmias and decreased heart rate variability when compared to subjects without a known deficit in control of breathing, and that these abnormalities would be exaggerated by anesthesia. Continuous ambulatory Holter recordings were obtained in patients with CCHS and compared to two otherwise healthy control groups without a deficit in control of breathing: one with an intact airway (n = 11) and a second group with a tracheostomy (n = 6). Holter recordings were obtained before, during (under general anesthesia), and after bronchoscopy. Fourteen children with CCHS (age: 9.3 +/- 4.4 years mean +/- S.D.) were studied, and 7 underwent bronchoscopy. Seventeen control children were studied (age 6.6 +/- 3.6 years): 11 without a tracheostomy, and 6 with a tracheostomy who also underwent bronchoscopy. Maximum heart rate during baseline recording was significantly lower in the CCHS subjects as compared to controls (P = 0.0001). At baseline the difference in the number of arrhythmias/24 hr/subject in all CCHS vs. all control subjects was significant (P = 0.0002); for the subjects who had bronchoscopy, CCHS vs. control, the difference was also significant (P = 0.03). In addition, there was a significant decrease in the number of events/24 hr/subject among the CCHS subjects between baseline and post-bronchoscopy (P = 0.0288). The predominant arrhythmias were sinus bradycardia and transient asystole. The longest asystole in a CCHS subject was 6.50 sec, and in a control subject, 1.42 sec (at baseline the means of the longest asystole were 2.69 +/- 1.4 vs. 1.24 +/- 0.13; P = 0.003 in the CCHS vs. control groups). Other indices of heart rate variability were significantly reduced in the CCHS subjects (P < 0.05). These results substantiate our hypothesis that subjects with CCHS have more arrhythmias than controls, an increased frequency of bradyarrhythmias, and decreased cyclical sinus arrhythmia.

Prenatal cocaine exposure reduces glial cell line-derived neurotrophic factor (GDNF) in the striatum and the carotid body of the rat: implications for DA neurodevelopment.

Glial cell line-derived neurotrophic factor (GDNF) is a glycosylated, disulfide-bonded homodimer, and a member of the transforming growth factor-beta superfamily. GDNF has been shown to promote the survival and morphological differentiation of dopamine (DA) neurons and increase their high-affinity dopamine uptake. In order to determine whether the mechanism for our previously observed cocaine-induced DA reductions in brain and carotid body were GDNF-mediated, we exposed Sprague-Dawley rat fetuses to cocaine via maternal subcutaneous injections (30 mg/kg b.i.d., E7-E19). Brains and carotid bodies of fetuses were excised and processed for assessment of GDNF levels using an Enzyme-Linked ImmunoadSorbent Assay (ELISA). ANOVA indicated that cocaine reduced carotid body GDNF by 36% (F((1,5))=28. 11, p<0.05) and striatal GDNF by 41% (F((1,5))=41.77, p<0.01). Although there was no interaction between drug exposure and fetal uterine position, post-hoc pairwise comparisons indicated that reductions in GDNF in the cocaine groups were due to differences at more distal positions (positions 4-8). The magnitude of the reductions in striatal GDNF (but not carotid body GDNF) in both cocaine-exposed and control fetuses followed a cervical (smallest GDNF reductions) to ovarian (greatest GDNF reductions) uterine position gradient. This pattern was similar to that which we observed in prior studies examining DA reductions in brain following prenatal cocaine exposure. The finding that cocaine reduces GDNF levels in striatum and carotid body support the hypothesis that cocaine's ability to reduce striatal and carotid body DA may be indirect through its ability to reduce GDNF. These data along with previous findings support the hypothesis that cocaine's effects on DA neurons are at least partially due to its indirect effects on trophic activity. The possible mechanisms whereby cocaine affects trophic activity are discussed.

Longitudinal assessment of hemoglobin oxygen saturation in healthy infants during the first 6 months of age. Collaborative Home Infant Monitoring Evaluation (CHIME) Study Group.

Limitations in home monitoring technology have precluded longitudinal studies of hemoglobin oxygen saturation during unperturbed sleep. The memory monitor used in the Collaborative Home Infant Monitoring Evaluation addresses these limitations. We studied 64 healthy term infants at 2 to 25 weeks of age. We analyzed hemoglobin oxygen saturation by pulse oximetry (SpO(2)), respiratory inductance plethysmography, heart rate, and sleep position during 35, 127 epochs automatically recorded during the first 3 minutes of each hour. For each epoch baseline SpO(2) was determined during >/=10 s of quiet breathing. Acute decreases of at least 10 saturation points and <90% for >/=5 s were identified, and the lowest SpO(2) was noted. The median baseline SpO(2) was 97.9% and did not change with age or sleep position. The baseline SpO(2) was <90% in at least 1 epoch in 59% of infants and in 0.51% of all epochs. Acute decreases in SpO(2) occurred in 59% of infants; among these, the median number of episodes was 4. The median lowest SpO(2) during an acute decrease was 83% (10th, 90th percentiles 78%, 87%); 79% of acute decreases were associated with periodic breathing, and >/=16% were associated with isolated apnea. With the use of multivariate analyses, the odds of having an acute decrease increased as the number of epochs with periodic breathing increased, and they lessened significantly with age. We conclude that healthy infants generally have baseline SpO(2) levels >95%. The transient acute decreases are correlated with younger age, periodic breathing, and apnea and appear to be part of normal breathing and oxygenation behavior.

SIDS risk factor awareness: assessment among nursing students.

OBJECTIVE: To test the hypotheses that nursing students (a) have limited knowledge of risk factors for sudden infant death syndrome (SIDS) and the American Academy of Pediatrics (AAP) recommendation of placing infants on their backs or sides for sleep, and (b) after careful education about SIDS, would retain this information and teach it to parents. DESIGN: A pretest questionnaire was used to identify knowledge of 13 risk factors and personal recommendation for sleep position. Participants attended a lecture on SIDS and received written educational material. A posttest was completed after 6 weeks. SETTING: Nursing students were assessed during their family practice course. PARTICIPANTS: Fifty-one 4th-year nursing students (mean age 28.4 years, SD=7.6) enrolled in the BSN program completed the pretest; 29 completed the identical posttest. INTERVENTION: A lecture on SIDS and SIDS risk factors with written educational material after the pretest. MAIN OUTCOME MEASURES: Pretest and posttest responses. RESULTS: The Mann-Whitney test and McNemar chi-square analyses were used to determine factors on the pretest which influenced the awareness of prone position and to compare pretest and posttest data. On the pretest, 69% of students were aware of the AAP recommendation but significantly more (92%) were aware on the posttest. Posttest responses increased significantly for 12 of the 13 risk factors; 41% of the students identified all 13 risk factors on the posttest, in contrast to 0% on the pretest. On both the pretest and posttest, 93% of students stated that it was important to discuss their infant's sleep position with parents. Posttest results showed that students unanimously recommend the side or back sleep position. CONCLUSION: Nursing students were aware of the AAP recommendation, yet their knowledge of other risk factors was limited. A careful educational process resulted in retention of information about the AAP recommendation and other risk factors. In addition, students were willing to teach parents to place their infants on the back or side to sleep.

The magnitude of brain dopamine depletion from prenatal cocaine exposure is a function of uterine position.

Cocaine's teratogenicity remains equivocal in the literature. The variance in cocaine-induced teratogenic data led us to consider that the intrauterine exposure to cocaine is not homogeneous and that sampling methods presently utilized in the literature lead to inconsistent results. Cocaine's vasoconstrictive actions, in concert with regional variance in the uterine milieu of the rodent, were postulated to differentially reduce the distribution of cocaine to fetal brains as a function of uterine position. Fetuses in positions with the highest levels of cocaine exposure were also hypothesized to have the most pronounced deficits in whole brain dopamine (DA). The results indicated that whole brain cocaine levels vary significantly in relation to a fetus' position in the uterine horn following a single SC injection of 30 mg/kg cocaine HCI as measured by GC/MS. Brains of fetuses from the most proximal uterine position (in relation to the cervix) received an average of 329% of the cocaine of fetuses from the most distal uterine position, whereas no such relationship existed for amniotic fluid cocaine levels. Following exposure to cocaine from embryonic days 7 to 21, brain DA levels were significantly reduced in distal fetuses relative to proximal fetuses and to distal controls. Contrary to the initial hypothesis, the results indicated that the magnitude of cocaine exposure was inversely related to the magnitude of DA reduction. Based upon findings in the literature related to the uterine gradient of placental progesterone distribution in the rat, cocaine's ability to lower brain DA levels was attributed primarily to its vasoconstrictive actions. Recommendations on how to statistically treat littermates, when foreknowledge of uterine position exists, are discussed.

Uterine position determines the extent of dopamine reduction after chronic prenatal cocaine exposure.

Most studying the consequences of prenatal cocaine (COC) exposure employ rodents or other multiparous organisms in their models. We have previously shown that when pregnant Sprague-Dawley albino rats are administered a 30 mg/kg subcutaneous (s.c.) injection on embryonic day 15 (E15), fetal brain COC levels show a proximal-to-distal (in relation to the cervix) gradient that can vary by as much as 350%. The present study sought to determine whether this gradient translated into a similar gradient in brain dopamine (DA) levels. Pregnant rats were administered COC or saline (SAL) (30 mg/kg COC or 1 ml/kg SAL, b.i.d., E7-E19). On E20, dams were anesthetized with halothane, the fetuses immediately removed, their brains excised, frozen and subsequently processed for DA, dihydroxyphenylacetic acid (DOPAC) or homovanillic acid (HVA). High-performance liquid chromatography (HPLC) analysis revealed a proximal-to-distal gradient for DA in both COC- and SAL-exposed fetuses. Average fetal DA levels per litter were significantly lower in COC-exposed litters (57.39 +/- 3.67 ng/hemibrain SAL; 48.29 +/- 3.87 ng/hemibrain COC F7,1 = 11.66, p < 0.05). The gradients for DA were in opposite directions such that COC litters showed the lowest levels of DA in the most distal uterine positions, whereas SAL-exposed litters showed the highest DA levels in the same location. These data suggest that a gradient in brain dopamine normally exists for fetuses based upon uterine position, and that cocaine can have selectively greater effects on this level as a function of fetal location.

Influence of increased survival in very low birth weight, low birth weight, and normal birth weight infants on the incidence of sudden infant death syndrome in the United States: 1985-1991.

OBJECTIVE: To examine the relationship between infant survival and the rates sudden infant death syndrome (SIDS) in very low birth weight (VLBW), low birth weight (LBW), and normal birth weight (NBW) infants from 1985 to 1991. METHODS: The National Center for Health Statistics Birth Cohort Linked Birth/Infant Death Data Sets were used to determine birth weight, age at death, and cause of death for US-born singleton infants with birth weights of 500 g or more. RESULTS: Increasing infant and postneonatal survival rates were greatest in VLBW infants. In contrast, SIDS rates did not change in VLBW infants (3.66 to 3.69; P = .70) but declined in both LBW (3.51 to 3.32; P = .041) and NBW (1.07 to 1.03; P = .008) infants. Postneonatal SIDS rates (per 1000 neonatal survivors) did not change in VLBW (4.93 to 4.58; P = .58) or LBW (3.36 to 3.22; P = .07) infants but declined in NBW infants (1.00 to 0.97; P = .018). Although there were differences among the slopes of survival rates, there was no statistical evidence of differences in the slope of SIDS rates among the three groups. CONCLUSIONS: The marked increase in survival of VLBW infants increased the pool of babies at potential risk for SIDS. VLBW infants' SIDS rates have not changed while they have declined in NBW and LBW infants.