Risk Of Sudden Infant Death Syndrome Research Articles

Maternal occupation and infant mortality in Japan: Insights from the Vital Statistics (Occupational and Industrial Aspects)

Objectives The proportion of Japanese women who maintain their employment during pregnancy and after delivery has been increasing. Previous studies from Western countries showed an association between the mother's occupation and birth outcomes; however, to the best of our knowledge, no epidemiological study has analyzed this association in Japan. Therefore, data from the national Vital Statistics: Occupational and Industrial Aspects were used to examine the association between the mother's occupation and (1) the risk of stillbirth at or after 12 weeks of gestation, and (2) the risk of infant death under 1 year of age after livebirth.Methods Data from the Vital Statistics: Occupational and Industrial Aspects (Live Birth Form, and Foetal Death Form) for fiscal years (FYs) 1995, 2000, 2005, 2010, and 2015 and Vital Statistics data files (Death Form) from FYs 1995-96, 2000-01, 2005-06, 2010-11, and 2015-16 were analyzed. The study population consisted of (1) 5,355,881 infants who were born during the survey period, with (2) 5,290,808 live birth excluding still birth during the same period. The odds ratios (ORs) were estimated for (1) stillbirth (without stillbirth = livebirth) and (2) infant death (without infant death = alive at 1 year of age) by mother's occupation (managers/specialist/technical workers, clerical workers, sales workers, service workers, blue collar workers, and not employed) using logistic regression. Blue collar workers included workers in security, agriculture/forestry/fishing, manufacturing process, transport, and machine operation. The population attributable risk (PAR) for stillbirth attributed to mother's occupation among employed mothers was also calculated.Results There were 61,179 (1.1%) stillbirths in the study population and 12,789 (0.2%) infant deaths among 5,290,808 live birth. Compared to managers/specialist/technical workers, the adjusted ORs (95% confidence interval) for stillbirth among clerical workers, sales workers, service workers, blue collar workers and not employed women were 1.24 (1.20-1.29), 1.48 (1.41-1.56), 1.76 (1.69-1.83), 1.54 (1.46-1.61), and 0.95 (0.92-0.98), respectively. There was no association between the mother's occupation and infant deaths. The PAR values for stillbirth among mothers employed as clerical workers and service workers were 7.4% and 12.3%.Conclusion The risk of stillbirth differed according to the mother's occupation in our study. The OR and PAR of stillbirth were the highest for service workers. Mother's occupation was not associated with the risk of infant death; therefore, the mothers' occupation is likely to affect the children's condition only during pregnancy. Our study suggests the importance of understanding the causal linkage between pregnant women's occupation and birth outcomes.

Characteristics and predictors of mortality in-hospital mortality following burn injury in infants in a resource-limited setting

PurposeBurn outcome data in infants is lacking from sub-Saharan Africa. We, therefore, sought to assess the characteristics and predictors of in-hospital burn mortality in a resource-limited setting. MethodsWe performed a retrospective study of the prospectively collected Burn Injury Surveillance database from June 2011 to December 2019. We performed bivariate analysis and Poisson regression to assess risk factors for mortality in our infant burn population. Results115 (7.3%) infants met inclusion criteria. The median age of 8 months (IQR: 6–10) and primarily male (n = 67, 58.8%). Most burns were from scald (n = 62, 53.9%). Infant burn mortality was 12.2%. Poisson multivariable regression to determine burn mortality risk in infants showed that increased %TBSA burns (RR 1.04, 95% CI 1.01–1.07) and flame burns (RR 3.08, 95%CI 1.16–8.16) had a higher risk of mortality. Having surgery reduced the relative risk of death for infants with burns. ConclusionWe show that factors that increase infant burn mortality risk include percent total body surface area burn, flame burn mechanism, and lack of operative intervention. Increasing burn operative capability, particularly for infants and other children, is imperative.

PIH4 Cost-Effectiveness of Rapid Screening in Antenatal Care in Bugesera District, Rwanda

Despite existing tools, malaria, HIV, syphilis, and hepatitis in pregnancy remain risks to the future infant. Currently, Rwanda routinely screens only for HIV in antenatal care (ANC). In 2019, Bugesera District initiated rapid ANC screening in 8 new health posts for all 4 infections. We sought to assess the cost-effectiveness of this initiative, beginning with the malaria component. To determine cost, we combined expenses of the test, its administration, and follow up treatment. We conducted a systematic literature review of the risk of infant death from malaria (PROSPERO registration 224460) to assess effectiveness. We assessed the risk of bias and applied the results to the local context (with ranges for uncertainty) using literature and expert opinion. Key parameters included the infant mortality rate per 1,000 births (IMR), life expectancy, ANC prevalence of malaria, and treatment success. The literature search yielded 130 unduplicated potentially relevant studies with key findings from one large unbiased study from Mozambique by Bardaji et al (2011). Its IMR was 112 among infants born to women with malarial infection compared to 58 overall, giving an odds ratio of 1.931. In Bugesera District, the IMR was 37, the prevalence of malaria infection in ANC screening was 1%-3%, the likelihood that a positive malaria test led to successful treatment 50%-100%, and the cost per test was $1-$3. These yielded 0.17-1.03 infant deaths averted, each avoiding 29.0 disability-adjusted life years (DALYs), per 1,000 women screened. The incremental cost-effectiveness ratio (ICER) per DALY averted was $221 (range $29-$579). As Rwanda’s 2019 per capita Gross National Income (GNI) was $820, the ICER was only 27% (range 4%-71%) of Rwanda’s per capita GNI—a desirably low multiple. ANC screening for malaria appears highly cost-effective in this Rwanda district and the approach is applicable to the other infections.

Housing conditions and adverse birth outcomes among Indigenous people in Canada.

ObjectivesPoor housing conditions and household crowding have been identified as important health concerns for Indigenous populations in many countries but have not been explored in relation to adverse birth outcomes in these populations. We investigated housing conditions and adverse birth outcomes in a nationally representative sample of Indigenous people in Canada.MethodsData were from a cohort of births between May 2004 and May 2006 created by linking birth and infant death registration data with the 2006 Canadian census. Log-binomial regression was used to examine associations between housing variables (persons per room and needed household repairs) and three adverse birth outcomes: preterm birth (PTB), small-for-gestational-age (SGA) birth, and infant mortality. Separate regression models were run for First Nations, Métis and Inuit mothers, with adjustment for parity and parental socio-economic variables.ResultsNeed for major household repairs was associated with a slightly increased risk of PTB among First Nations and Métis mothers (adjusted RRs 1.12 and 1.13, respectively; 95% CI 0.94–1.34 and 0.89–1.44, respectively) and a moderately increased risk of infant death in all three groups (aRR = 1.69, 95% CI 1.00–2.85). Household crowding was also associated with a slightly elevated risk of PTB in all three groups (aRR = 1.10, 95% CI 0.95–1.29) and with an increased risk of infant mortality among First Nations (aRR = 1.57, 95% CI 0.97–2.53).ConclusionThis study highlights the need to improve understanding of links between housing conditions and perinatal health outcomes in Indigenous populations, including examining cause-specific infant mortality in relation to housing characteristics.Supplementary InformationThe online version contains supplementary material available at 10.17269/s41997-021-00527-2.

Sudden infant death syndrome: deletions of glutathione-S-transferase genes M1 and T1 and tobacco smoke exposure

In developed countries, sudden infant death syndrome (SIDS) is the leading cause of death in infants in their first year of life. The risk of SIDS is increased if parents smoked during pregnancy and in presence of the child. Glutathione S-transferases (GSTs) catalyse the conjugation of glutathione with electrophilic compounds and toxins, making them less reactive and easier to excrete. As a gene dose effect was observed for GSTM1 and GSTT1, the aim of this study was to investigate whether there is a connection between homozygous or heterozygous gene deletions of GSTM1 or GSTT1 and the occurrence of SIDS. We found that heterozygous deletion of GSTM1 occurred significantly more frequently in the SIDS case group compared to the control group. A homozygous deletion of GSMT1 was slightly more frequently in the control group. A homozygous gene deletion of GSTT1 showed no significant difference between the SIDS group and the control group. We also found that in the SIDS group, the number of victims that were exposed to cigarette smoke was significantly higher than the number of victims without cigarette smoke exposure and that the mean lifetime of children whose mothers smoked was shorter in comparison with non-smoking mothers. In SIDS cases with homozygous gene deletions of GSTM1, the median life span of children with tobacco smoke exposure was 60 days shorter than without smoke exposure. In conclusion, the absence of these two genes is not the only trigger for SIDS but could be a critical aspect of SIDS aetiology, particularly in SIDS cases with smoking parents.

Increased brainstem microglia is associated with an attenuated hypercarbic ventilatory response in a rat model of neonatal opioid withdrawal syndrome

Background Infants born with neonatal opioid withdrawal syndrome (NOWS) display abnormal respiratory patterns including tachypnea, apnea and impaired ventilatory responses to hypoxia and hypercarbia challenges. Infants with NOWS are also at an increased risk of sudden infant death syndrome (SIDS), which is associated with impairments in respiratory control and increased gliosis in key brainstem respiratory control regions including the nucleus tractus solitarius (nTS). Objective Use a rat model of neonatal opioid withdrawal syndrome to assess whether pre- and postnatal morphine exposure attenuates the ventilatory responses to hypoxia and hypercarbia challenges in the offspring and whether they are associated with increased nTS microglia expression. Design/Methods Pregnant female rats (dams) received twice-daily subcutaneous injections of morphine (5mg/kg) during the third (last) week of pregnancy to simulate 3rd trimester in utero opioid exposure. After birth, the pups received once-daily subcutaneous injections of morphine (1mg/kg), through postnatal day 10 to simulate postnatal morphine therapy. Whole-body plethysmography was used precisely 24 hours later to assess ventilatory defense responses to acute hypoxia (HVR) and hypercapnia (HCVR) challenge (5 minutes at 10% O2 and 5% CO2, respectively). Brainstems were removed to assess nTS microglia expression using immunohistochemistry and a glial (Iba-1) marker. Results Compared to saline-treated pups, morphine exposure attenuated the HCVR, but not the HVR (Fig. 1A). Morphine-exposed offspring also expressed increased number of microglia in the nTS (Fig. 1B). Conclusion The disturbances in neonatal hypercarbia challenge are associated with increased brainstem microglia expression, which could contribute to the etiology underlying the increased risk of SIDS in infants with NOWS.

Neuronal Loss in the Nucleus Tractus Solitarius and Associated Disturbances of the Hypoxic Ventilatory Response in Rat Offspring Following in‐utero Morphine Exposure

The incidence of opioid use during pregnancy, including prescriptions, has become a growing public health concern and has been linked to neonatal abstinence syndrome (NAS), poor neurodevelopmental outcome and increased risk of sudden infant death syndrome (SIDS). Abnormal cardiorespiratory regulation in infants born following in-utero opioid exposure includes reduced vagal tone, delayed arousal, and altered ventilatory responses to hypoxia and hypercapnia. Impairments in ventilatory defense responses and abnormal development of brainstem cardiorespiratory control regions may contribute to infant vulnerability and dampen responses to exogenous stressors leading to SIDS. Although infants with NAS may be treated with morphine, not all infants require pharmacologic treatment. To mimic the latter group of infants, we used a rat model of in utero morphine exposure to investigate the long-term effects it has on respiratory control and brainstem neuronal development of the offspring. Using a rat model of in utero morphine exposure to characterize long-term (10 days) effects on the offspring including: 1) the acute hypoxic (HVR) and hypercapnic ventilatory response (HCVR) as indices of respiratory control (dys)function; and 2) brainstem neuron counts as an indicator of neural development. Pregnant dams received twice daily (morning and afternoon) subcutaneous injections of various doses of morphine (0.5, 1, and 5mg/kg) or saline (control group) during the final week of pregnancy to mimic 3rd trimester maternal opioid use. Following birth, nursing dams and rat pups were left untreated. On postnatal day 10, whole body plethysmography was used to assess the HVR and HCVR in the pups. Brains were removed and prepared for immunohistochemical assessment of neuron cell counts in key brainstem cardiorespiratory control regions. In-utero morphine exposure at any dose (0.5, 1, 5mg/kg) caused a long-term attenuation of the HVR (Fig. 1A), but not the HCVR when compared to pups from in-utero saline treated rats. At the highest dose (5mg/kg), neuron cell numbers were reduced by approximately 50% compared to saline rats (Fig. 1B-C). These data demonstrate a long-term effect of in-utero morphine exposure on respiratory control, which may in part be explained by disrupted brainstem neural development. These cardiorespiratory anomalies could offer insight into the pathophysiology of the increased risk of SIDS seen in infants born from mothers with opioid use.

Bed sharing versus no bed sharing for healthy term neonates.

There isgreat global variation in the sleeping arrangements for healthy newborn infants. Bed sharingis a type of sleeping practice in which the sleeping surface (e.g. bed, couch or armchair, or some other sleeping surface) is shared between the infant and another person. The possible physiological benefits include better oxygen and cardiopulmonary stability, fewer crying episodes, less risk of hypothermia, and a longer duration of breastfeeding. On the other hand, the most important harmful effect of bed sharing is that it may increase the risk of sudden infant death syndrome (SIDS). Studies have found conflicting evidence regarding the safety and efficacy of bed sharing during infancy. To evaluate the efficacy and safety of bed sharing, started during the neonatal period, on breastfeeding status (exclusive and total duration of breastfeeding), incidence of SIDS, rates of hypothermia, neonatal and infant mortality, and long-term neurodevelopmental outcomes. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 7) in the Cochrane Library; MEDLINE via PubMed (1966 to 23 July 2020), CINAHL (1982 to 23 July 2020), and LILACS (1980 to23 July 2020). We also searched clinical trials databases, and the reference lists of retrieved articles, for randomised controlled trials (RCTs) and quasi-RCTS. We planned to include RCTs or quasi-RCTs (including cluster-randomised trials) that included term neonates initiated on bed sharingwithin 24 hours of birth (and continuing to bed share with the mother in the first four weeks of life, followed by a variable time period thereafter), and compared them to a 'no bed sharing' group. We used standard methodological procedures as recommended by Cochrane. We planned to use the GRADE approach to assess the certainty of evidence. Our search strategy yielded 6231 records. After removal of duplicate records, we screened 2745 records by title and abstract. We excluded 2739 records that did not match our inclusion criteria. We obtained six full-text studies for assessment. These six studies did not meet the eligibility criteria and were excluded. We did not find any studies that met our inclusion criteria. There is a need for RCTs on bed sharing in healthy term neonates that directly assess efficacy (i.e. studies in a controlled setting, like hospital) or effectiveness (i.e. studies conducted in community or home settings) and safety. Future studies should assess outcomes such asbreastfeeding status and risk of SIDS. They should alsoinclude neonates fromhigh-income countries and low- and middle-income countries, especially those countries wherebed sharing is more prevalent because of cultural practices (e.g. Asian countries).

Does Bed-Sharing Increase the Risk for Sudden Infant Death Syndrome? - A Review of the Literature and Official Guidelines of Selected EU Countries

In Europe in 2015, 726 infants died of sudden infant death syndrome (SIDS). Bed-sharing is often discussed as a risk factor for SIDS. This paper examines the evidence on the impact of bed-sharing on the risk of SIDS and considers the official recommendations of individual EU countries on safe infant sleep. An integrative literature review was conducted. The Cochrane Library, Pubmed, CINAHL, and MIDRIS databases were searched using the keywords "Sudden Infant Death Syndrome", "SIDS", bed sharing", "breastfeeding" and "baby sleep" for articles in the German or English language that were published between 2012 and February 2019. In a second step, official recommendations for safe baby sleep from 6 EU countries were analyzed. The risk for SIDS in bed-sharing three months postpartum is not higher in the absence of risk factors. Not all EU country recommendations on bed-sharing and SIDS differentiate between bed-sharing in the first 3 months of the baby's life and bed-sharing with babies 3 months or older. Parents and health care professionals need evidence-based information to optimize the newborn baby's sleeping environment. Official recommendations on safe baby sleep should be assessed in regards to their congruence with current research findings on bed-sharing and SIDS.

Sudden Infant Death Syndrome: Beyond Risk Factors

Sudden infant death syndrome (SIDS) is defined as “the sudden death of an infant under 1 year of age which remains unexplained after thorough investigation including a complete autopsy, death scene investigation, and detailed clinical and pathological review”. A significant decrease of SIDS deaths occurred in the last decades in most countries after the beginning of national campaigns, mainly as a consequence of the implementation of risk reduction action mostly concentrating on the improvement of sleep conditions. Nevertheless, infant mortality from SIDS still remains unacceptably high. There is an urgent need to get insight into previously unexplored aspects of the brain system with a special focus on high-risk groups. SIDS pathogenesis is associated with a multifactorial condition that comprehends genetic, environmental and sociocultural factors. Effective prevention of SIDS requires multiple interventions from different fields. Developing brain susceptibility, intrinsic vulnerability and early identification of infants with high risk of SIDS represents a challenge. Progress in SIDS research appears to be fundamental to the ultimate aim of eradicating SIDS deaths. A complex model that combines different risk factor data from biomarkers and omic analysis may represent a tool to identify a SIDS risk profile in newborn settings. If high risk is detected, the infant may be referred for further investigations and follow ups. This review aims to illustrate the most recent discoveries from different fields, analyzing the neuroanatomical, genetic, metabolic, proteomic, environmental and sociocultural aspects related to SIDS.

Gene variants associated with obstructive sleep apnea (OSA) in relation to sudden infant death syndrome (SIDS)

BackgroundBoth obstructive sleep apnea (OSA) and (at least a fraction of) sudden infant death syndrome (SIDS) are associated with impaired respiration. For OSA, an association with several gene variants was identified. Therefore, our hypothesis is that these polymorphisms might be of relevance in SIDS as well.MethodsTwenty-four single nucleotide polymorphisms (SNPs) in 21 candidate genes connected to OSA, were genotyped in a total of 282 SIDS cases and 374 controls. Additionally, subgroups based on factors codetermining the SIDS risk (age, sex, season, and prone position) were established and compared as well.ResultsTwo of the analyzed SNPs showed nominally significant differences between SIDS and control groups: rs1042714 in ADRB2 (adrenoceptor beta 2) and rs1800541 in EDN1 (endothelin 1). In the subgroup analyses, 10 further SNPs gave significant results. Nevertheless, these associations did not survive adjustment for multiple testing.ConclusionsOur results suggest that there might be a link between SIDS and OSA and its resulting respiratory and cardiovascular problems, albeit this predisposition might be dependent on the combination with other, hitherto unknown gene variants. These findings may encourage replication studies to get a better understanding of this connection.

Association between monoamine oxidase A promoter polymorphism and the risk of sudden infant death syndrome: a meta-analysis

IntroductionThe etiology of sudden infant death syndrome (SIDS) remains an unsolved problem. The aim of this meta-analysis is to investigate the potential association between monoamine oxidase A (MAOA) promoter variable number tandem repeat (VNTR) polymorphism and SIDS risk.MethodsA systematic review and meta-analysis were conducted on studies from accessible electronic databases. Each VNTR variant was examined in each gender independently by comparing with the pooled results of other alleles.ResultsA total of six independent case–control studies including 1022 SIDS cases and 1839 controls were enrolled in this meta-analysis. In both of the whole populations and Caucasian populations, male infants with the low-MAOA-expression alleles (2R+3R) were found to exhibit a statistically significant increased risk of SIDS, whereas those with a 4R allele exhibited a reduced risk of SIDS. Besides, an increased risk of SIDS was detected in male Caucasian infants with 2R or 3R alleles. However, none of the allele or genotype variants was associated with SIDS in female victims.ConclusionIn male Caucasian infants, the low expression of MAOA promoter VNTR alleles (2R and 3R) is associated with an increased risk of SIDS, and the existence of the 4R allele could be regarded as a protective factor.

973 The risk of perinatal mortality by week of expectant management in pregnancies complicated by diabetes

The optimal timing of delivery of pregnancies complicated by diabetes is unknown. The risk of neonatal morbidity and mortality decreases with advancing gestation, which is countered by an increased risk of stillbirth. The objective of this study was to compare the risk of stillbirth and infant death per week of expectant management versus delivery in pregnancies complicated by pregestational (PGD) and gestational diabetes (GDM). A population based retrospective cohort study of non-anomalous singleton pregnancies complicated by either PGD or GDM was performed using national linked birth and death certificate data from 2014-2016. The incidences of stillbirth and neonatal death were determined for each week of pregnancy from 34 to 40 completed weeks’ gestation. A composite perinatal mortality risk with each week of expectant management was calculated by adding the risk of still birth in a given week to the neonatal death risk of delivery in the following week. The relative risk (RR) and 95% confidence interval (CI) of perinatal mortality with expectant management versus delivery was calculated comparing the composite perinatal mortality with the neonatal death risk of delivery in the same week. A total of 989,477 pregnancies were included (PGD: 12.6%, GDM: 87.4%). For both PGD and GDM pregnancies, the risk of stillbirth increased while the risk of infant death decreased with advancing gestation; Table 1. In PGD pregnancies, the risk of neonatal mortality was significantly lower at 37 weeks’ gestation compared to the composite perinatal mortality, favoring delivery over expectant management (RR: 0.52; CI: 0.38-0.71). For GDM pregnancies, this risk was significantly reduced with immediate delivery at 38 weeks’ gestation (RR: 0.48; CI: 0.40-0.59); Figure 1. There does not appear to be a benefit for iatrogenic preterm delivery in either PGD or GDM pregnancies, with results favoring delivery at 37 and 38 weeks’ gestation respectively. This data does not consider glycemic control and delivery timing should be individualized.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Automatic baby incubator system with fuzzy-PID controller

Deaths due to temperature instability often occur in premature babies. Negligent handling of new-borns can pose a risk of temperature instability as well. Therefore, interventions to keep the baby’s body temperature warm can reduce the risk of infant death. An incubator is a box equipped with a temperature controller to maintain a baby’s average body temperature. The faster nursery controlled the heat, the quicker the handling of the baby from the risk of temperature instability. This research aims to design a baby incubator that has an automatic control system for working temperatures quickly. The method to be used is Fuzzy-PID control, which functions to maintain temperature stability and accelerate the system’s response to the incubator. The temperature in the nursery is measured using a DHT22 sensor. The temperature measured from the sensor use error and delta error as input parameters in the design of the fuzzy membership set. The heater used in this study is an incandescent lamp to produce heat that is safe for babies. An experiment was carried out by comparing the PID control to determine the speed of the system response. Besides, measurements to assess the stability of the controller are also carried out by analyzing the effect of the load on temperature variations. The test results show a faster system response compared to the PID control and stability at a temperature set point of 32 ° C, 33 ° C, 34 ° C and 35 ° C. The time needed to achieve balance at the highest temperature of set points is 205 seconds with a max overshoot of 0.5%. With the max overshoot, the incubator can still work at a temperature that is safe for babies.

The Unfolded Protein Response in the Human Infant Brain and Dysregulation Seen in Sudden Infant Death Syndrome (SIDS).

Low orexin levels in the hypothalamus, and abnormal brainstem expression levels of many neurotransmitter and receptor systems in infants who died suddenly during a sleep period and diagnosed as sudden infant death syndrome (SIDS), may be linked to abnormal protein unfolding. We studied neuronal expression of the three unfolded protein response (UPR) pathways in the human infant brainstem, hypothalamus, and cerebellum: activating transcription factor 6 (ATF6), phosphorylated inositol-requiring enzyme 1 (IRE1), and phosphorylated protein-kinase (PKR)-like endoplasmic reticulum (ER) kinase (pPERK). Percentages of positively stained neurons were examined via immunohistochemistry and compared between SIDS (n = 28) and non-SIDS (n = 12) infant deaths. Further analysis determined the effects of the SIDS risk factors including cigarette smoke exposure, bed-sharing, prone sleeping, and an upper respiratory tract infection (URTI). Compared to non-SIDS, SIDS infants had higher ATF6 in the inferior olivary and hypoglossal nuclei of the medulla, higher pIRE1 in the dentate nucleus of the cerebellum, and higher pPERK in the cuneate nucleus and hypothalamus. Infants who were found prone had higher ATF6 in the hypoglossal and the locus coeruleus of the pons. Infants exposed to cigarette smoke had higher ATF6 in the vestibular and cuneate nuclei of the medulla. Infants who were bed-sharing had higher pPERK in the dorsal raphe nuclei of the pons and the Purkinje cells of the cerebellum. This study indicates that subgroups of SIDS infants, defined by risk exposure, had activation of the UPR in several nuclei relating to proprioception and motor control, suggesting that the UPR underlies the neuroreceptor system changes responsible for these physiological functions, leading to compromise in the pathogenesis of SIDS.

Melatonin protects against environmental stress-induced fetal growth restriction via suppressing ROS-mediated GCN2/ATF4/BNIP3-dependent mitophagy in placental trophoblasts

Gestational exposure to environmental stress induces fetal growth restriction (FGR), and thereby increasing the risk of infant death and chronic noncommunicable diseases in adults. However, the mechanism by which environmental stress induces FGR remains unclear. Based on case-control study, we found that the reduced level of melatonin (MT), a major secretory product from the pineal gland, was observed in placentae of FGR. This work was to investigate the protective effect of MT on environmental stress-caused FGR and its mechanisms. We used cadmium (Cd) as an environmental stressor to stimulate pregnant mice and thereby establishing a FGR model. The data showed that maternal Cd exposure lowered the P4 concentration in maternal sera, placentae and amniotic fluid, and caused FGR. Correspondingly, the expression of CYP11A1, a critical P4 synthase, was markedly downregulated in Cd-treated placentae. Simultaneously, Cd triggered BNIP3-dependent mitophagy in placental trophoblasts, as determined by the degradation of mitochondrial proteins, including HSP60 and COX IV, and the accumulation of puncta representing co-localization of TOM20 with LC3B or BNIP3 with LC3B. Based on our case-control study, we also found that activated BNIP3-dependent mitophagy and P4 synthesis inhibition occurred in SGA placentae. Most importantly, BNIP3 siRNA reversed Cd-induced P4 synthesis suppression in human placental trophoblasts. It is noteworthy that MT alleviated Cd-caused P4 synthesis suppression and FGR via antagonizing BNIP3-dependent mitophagy in placental trophoblasts. Further results confirmed that MT attenuated Cd-triggered BNIP3-dependent mitophagy via blocking GCN2/ATF4 signaling. Amusingly, Cd triggered oxidative stress and then activating GCN2/ATF4 signaling in placental trophoblasts. As expected, MT obviously suppressed Cd-caused reactive oxygen species (ROS) release. In the present study, we propose a neoteric mechanism by which MT protects against environmental stress-impaired P4 synthesis and fetal growth via suppressing ROS-mediated GCN2/ATF4/BNIP3-dependent mitophagy in placental trophoblasts. As above, MT is a potential therapeutic agent antagonizing environmental stress-induced developmental toxicity.

Are Safe Sleep Practice Recommendations For Infants Being Applied Among Caregivers?

BackgroundSudden infant death syndrome (SIDS) is defined as the sudden unexpected death of an infant, even after investigations and autopsy. SIDS is related to many factors, such as the baby’s position and objects in the crib. Adherence to safe sleep recommendations in Saudi Arabia is unclear. This study aims to assess caregivers’ implementation of safe sleep practices and if they received any safe sleep education through health care workers.MethodsThis was a cross-sectional, descriptive study. Inclusion criteria included all infants below the age of one year. Exclusion criteria included infants who were born premature, used ventilation, had a tracheostomy, any anomaly in the upper airway, or underwent spine surgery. A semi-structured questionnaire was used. Data were collected from mothers who had infants visiting the outpatient department of King Abdulaziz University Hospital in Jeddah, Saudi Arabia. An electronic survey was also created and published on a social platform. Statistical analysis was conducted with the aid of the Statistical Package for Social Sciences (SPSS) software, version 26 (IBM SPSS Statistics, Armonk, NY).ResultsAmong 506 participants, only 22.5% were found to receive education about safe practices from health care providers. Fortunately, most of the infants (63.2%) were found to sleep in a supine position most of the nights. Adherent caregivers to placing the child in a designated baby bed and in a supine position most nights represented 44.86% of the sample. However, when asked about placing any of the following objects in the bed (pillows, blankets, soft toys, hard toys, and electric wires), the percentage of adherence dropped down to only 1.58%.ConclusionThere was an obvious non-adherence among caregivers and a possible lack of knowledge of safe sleep recommendations for infants. This highlights the need for optimal education by health care workers and the rule of media and campaigns is obvious and essential to improving their practices and, hopefully, decreasing the risk of SIDS.

Abstract 12824: Higher Prevalence of Qt Interval Prolongation in Infants With Intrauterine Tobacco Smoke Exposure

Background: The association between QT interval prolongation and sudden infant death syndrome (SIDS) has been clearly established. Environmental tobacco smoke (ETS) exposure is also associated with increased risk for SIDS. However, there has been little focus on the relationship between the QT interval and ETS exposure during early infancy. To clarify this, we examined the QT interval with ETS exposure during early infancy. Methods: A total of 2168 infants (age:1-4 months), 743 infants who have been exposed to tobacco smoking since intrauterine life and 1425 age-matched children without ETS exposure, underwent electrocardiographic study. QT data were extracted from the electrocardiogram monitor built-in echocardiogram. The QT interval was measured on the first, second, third, and fourth month. The corrected QT interval (QTc) was calculated by dividing the QT interval by the square root of the RR interval (Bazett’s formula). QT interval prolongation was defined as QTc≧440 msec. The data of the number of cigarettes per day were collected by a questionnaire. Results: In the total study population, the mean QTc in ETS infants was significantly greater than in infants without ETS (402±21 and 395±20 msec, p<0.01). The absolute risk of QT prolongation was 1.11 % (16/1425) in infants without ETS; by contrast, that of ETS infants with QTc≧440 msec was 3.23% (24/743) (odds ratio, 2.94; 95% confidence interval, 2.30 to 3.58). The mean QTc in ETS infants at the first, second and third month was significantly greater than that in infants without ETS (404±20 vs. 397±21 msec, 407±19 vs. 399 ±17 msec and 404±17 vs. 390±18 msec, p < 0.01, respectively), but the mean QTc at the fourth month was similar in the 2 groups. The odds ratios for QTc≧440msec in ETS infants at the second and third month were 7.15 (95% confidence interval, 6.00 to 8.29) and 4.97 (95% confidence interval, 2.74 to 7.18), respectively. Compared with infants without ETS, ETS infants with the number of cigarettes ≧10 cigarettes per day had a significantly higher risk of QTc≧440 msec(odds ratio: 3.32, 95% confidence interval: 2.67-3.99). Conclusions: The present study indicates that environmental tobacco exposure is a risk for QT interval prolongation ≧440msec during early infancy.

Birth Anthropometry Predicts Neonatal and Infant Mortality in Rural Bangladesh: A Focus on Circumferential Measurements

Background: Risk of infant death is increased in small newborns. Weight and length are typically measured at birth while circumferences are less often assessed. We investigated abilities of birth length, weight, and mid-upper arm (MUAC), head (HC) and chest (CC) circumferences to predict infant mortality in rural northwest Bangladesh. Methods: Singletons born during an antenatal micronutrient supplementation trial (n=21 174) were measured < 72 hours of birth. Vital status was prospectively recorded throughout infancy, identifying 583 deaths. Optimal cut-offs for predicting neonatal (NMR ≤28 days) and infant (IMR ≤365 days) mortality for each measurement were informed by the Youden Index (sensivity+specificity-1). Relative Risk Ratios (RRRs) and positive predictive values (PPVs) were calculated at cut-offs throughout the range of each measurement, and for indices combining any two. Results: Predictive cutoffs, harmonized to 100 g or 0·5 cm readings, for both NMR and IMR were 44.5 cm for length, 2200 g for weight, 9·0 cm for MUAC, 31·0 cm for HC, and for 28·5 cm CC. A CC <28·5 cm, alone and combined with HC <31·0 cm, versus higher values, yielded highest RRRs [9·68 (95% CI:7·84-11·94) and 15.74 (95% CI:12·54-19·75)] and PPVs (11·3% and 16·3%) for neonatal and infant [RRRs=6.02 (95% CI:5·15-7·02) and 9.19 (95% CI:7·72-10·95) and PPVs (10·7% and 14·6%)] mortality. At harmonized cut-offs, all indices revealed higher RRRs (range:5·34-9·19) and PPVs (range:8·5%-14·5%) than individual measurements (ranges:3·40-6·02 and 6·4%-16·3%, respectively). Conclusions: In rural Bangladesh, chest circumference alone or combined with head circumference was more predictive of neonatal and infant mortality than other measurements. Trial Registration: ClinicalTrials.gov INCT00860470 Funding Statement: Bill & Melinda Gates Foundation (Grants GH614 and OPP1441435, Senior Program Officer: Ellen Piwoz), Seattle, WA, USA and the Sight and Life Global Nutrition Research Institute (Klaus Kraemer), Baltimore MD. Declaration of Interests: None. Ethics Approval Statement: Verbal informed consent was obtained from mothers prior to enrollment in the trial. The study protocol was approved by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board, Baltimore, Maryland, and the Bangladesh Medical Research Council, Dhaka, Bangladesh.

Improving infant sleep safety via electronic health record communication: a randomized controlled trial

BackgroundWith increased use of telehealth, interventions to improve infant sleep environments have not been explored. This study sought to assess the feasibility and efficacy of using electronic health record patient portals to transmit photographs of infant sleep between mothers and healthcare professionals as part of an intervention to promote sleep environments consistent with AAP guidelines.MethodsOne hundred eighty-four mother-newborn dyads consented to participate in a randomized trial requiring patient portal registration within 1 month of delivery. We first assessed feasibility as measured by a) the proportion of consented mothers enrolling in the portal and b) maternal adherence to prompts to submit photographs of their infant sleeping to the research team through the patient portal. Intervention group mothers were prompted at 1 and 2 months; controls were prompted only at 2 months. Efficacy was determined via research assistant review of submitted photographs. These assistants were trained to detect sudden unexplained infant death risk factors utilizing AAP guidelines. Standardized feedback was returned to mothers through the patient portal. We used Fisher’s Exact test to assess group differences in guideline adherence at 2 months.ResultsOne hundred nine mothers (59%) enrolled in the patient portal and were randomized to intervention (N = 55) and control (N = 54) groups. 21 (38, 95% CI 25–52%) intervention group participants sent photographs at 1 month and received personalized feedback. Across both groups at 2 months, 40 (37, 95% CI 28–46%) sent photographs; 56% of intervention group participants who submitted photographs met all safe sleep criteria compared with 46% of controls (difference 0.10, 95% CI − 0.26 to 0.46, p = .75). Common reasons for guideline non-adherence were sleeping in a room without a caregiver (43%), loose bedding (15%) and objects (8%) on the sleep surface.ConclusionsUtilizing the patient portal to individualize safe infant sleep is possible, however, we encountered numerous barriers in this trial to assess its effects on promoting safe infant sleep. Photographs of infants sleeping showed substantial non-adherence to AAP guidelines, suggesting further needs for improvement to promote safe infant sleep practices.Trial registrationName: Improving Infant Sleep Safety With the Electronic Health Record; Clinicaltrials.gov: NCT03662048; Date of Registration: September 7, 2018;Data Sharing Statement: None