Infant Death Research Articles

The French registry of sudden unexpected death in infancy (SUDI): a 7-year review of available data.

This article details the objectives and methods of the French registry of SUDI. It provides initial results relating to thepopulation included in the register and the procedure for accessing the data. • In Western Europe, France is one of the countries with the highest SUDI rate, making it the first cause of death of infants between 28 and 364days. • The development of epidemiological tools on a national and international scale is essential to advance research into the determinants and risk factors of unexpected death in children under 2years of age. • The OMIN registry was created in France in 2015 to collect nationwide standardised social, environmental, clinical, and paraclinical data for cases of unexpected death in children aged 0 to 2years. • To date, the OMIN registry has included 680 data from almost 2000 children unexpectedly deceased, completed by a biocollection since 2020. • Data from the OMIN registry, unique in its field, are freely available for scientific research teams, after acceptation by the scientific committee of the registry.

GFAP expression in the brain during human postnatal development

AbstractGlial fibrillary acidic protein (GFAP) immunohistochemistry was investigated in the developing human brain using two measures; the number of GFAP‐positive cells (density, GFAP+/mm2), and a reactivity score (R‐score), which we recently introduced to indicate astrogliosis, with scores ≥120 indicative of pathological processes. The primary aim was to report on GFAP expression and cell soma size in 26 microscopically defined regions of the amygdala, basal ganglia, cerebellum, hippocampus and medulla, and to determine whether they are affected by postconceptional age (PCA) from 40 to 83 weeks. The secondary aim was to determine if GFAP expression differs according to the classification of sudden infant death syndrome (SIDS) as opposed to infant deaths of known causes, or for the presence of major SIDS risk factors of male sex, cigarette smoke exposure, upper respiratory tract infection (URTI), bed‐sharing and prone sleeping. The cerebellar molecular layer was void of GFAP+ cells, while the internal granular layer (IGL) had the highest density, with >60% of infants having an R‐Score >120. GFAP expression decreased with increasing PCA in the entorhinal and temporal cortex, subiculum and regions of the cerebellum and medulla. GFAP cell soma size corresponded with astrogliosis score and no effect of PCA was evident. Various region‐dependent GFAP expressional differences were seen according to SIDS classification and the risk factors studied. The findings indicate that the density of GFAP decreases in specific regions of the brain within the first year of postnatal development, and that reactive astrocytes are common, particularly within the early postnatal months.

Clinical predictors of poor outcome of bacterial meningitis in infants less than 90 days: a systematic review

Backgroundbacterial meningitis (BM) is more common in infants than at any other time in life and remains a devastating disease with considerable risk of death and morbidity. This article aims to gather the currently available evidence to perform a systematic review of clinical factors that may predict or be associated with BM death and/or sequelae in infants < 90 days of age.MethodsThe Medline/PubMed, Cochrane Library and Embase databases were systematically searched for prognostic studies that described risk factors for mortality and sequelae in infants aged <90d with BM. The databases were searched from the beginning of the database to December 31st, 2022.The quality of cohort studies was assessed by the Newcastle-Ottawa Scale (NOS). The quality of cross-section studies was assessed by the Agency for Healthcare Research and Quality (AHRQ). A systematic review was undertaken to ascertain the prognostic factors proven to be noteworthy.ResultsOf the 1,431 studies retrieved, 20 were eligible for the final analysis including 11 cohort and 9 cross-sectional studies were identified. Four risk factors predicting poor outcome were mentioned mostly in those studies, including prematurity or low birth weight (LBW), seizures, coma, and elevated CSF protein. But only preterm, coma and elevated CSF protein were identified by multivariate analyses in more than one study.ConclusionsThis study demonstrates several potential predictive factors to the poor outcomes of BM in infant. But with large heterogeneity, these predictors should be evaluated by further well-designed prospective studies.Systematic Review Registrationhttps://www.crd.york.ac.uk/, identifier CRD42017074949.

Vglut2-based glutamatergic signaling in central noradrenergic neurons is dispensable for normal breathing and chemosensory reflexes.

Central noradrenergic (NA) neurons are key constituents of the respiratory homeostatic network. NA dysfunction is implicated in several developmental respiratory disorders including Congenital Central Hyperventilation Syndrome (CCHS), Sudden Infant Death Syndrome (SIDS), and Rett Syndrome. The current unchallenged paradigm in the field, supported by multiple studies, is that glutamate co-transmission in subsets of central NA neurons plays a role in breathing control. If true, NA-glutamate co-transmission may also be mechanistically important in respiratory disorders. However, the requirement of NA-derived glutamate in breathing has not been directly tested and the extent of glutamate co-transmission in the central NA system remains uncharacterized. Therefore, we fully characterized the cumulative fate maps and acute adult expression patterns of all three vesicular glutamate transporters (Slc17a7 (Vglut1), Slc17a6 (Vglut2), and Slc17a8 (Vglut3)) in NA neurons, identifying a novel, dynamic expression pattern for Vglut2 and an undescribed co-expression domain for Vglut3 in the NA system. In contrast to our initial hypothesis that NA-derived glutamate is required to breathing, our functional studies showed that loss of Vglut2 throughout the NA system failed to alter breathing or metabolism under room air, hypercapnia, or hypoxia in unrestrained and unanesthetized mice. These data demonstrate that Vglut2-based glutamatergic signaling within the central NA system is not required for normal baseline breathing and hypercapnic, hypoxic chemosensory reflexes. These outcomes challenge the current understanding of central NA neurons in the control of breathing and suggests that glutamate may not be a critical target to understand NA neuron dysfunction in respiratory diseases.

Vglut2-based glutamatergic signaling in central noradrenergic neurons is dispensable for normal breathing and chemosensory reflexes

Central noradrenergic (NA) neurons are key constituents of the respiratory homeostatic network. NA dysfunction is implicated in several developmental respiratory disorders including Congenital Central Hyperventilation Syndrome (CCHS), Sudden Infant Death Syndrome (SIDS), and Rett Syndrome. The current unchallenged paradigm in the field, supported by multiple studies, is that glutamate co-transmission in subsets of central NA neurons plays a role in breathing control. If true, NA-glutamate co-transmission may also be mechanistically important in respiratory disorders. However, the requirement of NA-derived glutamate in breathing has not been directly tested and the extent of glutamate co-transmission in the central NA system remains uncharacterized. Therefore, we fully characterized the cumulative fate maps and acute adult expression patterns of all three vesicular glutamate transporters (Slc17a7 (Vglut1), Slc17a6 (Vglut2), and Slc17a8 (Vglut3)) in NA neurons, identifying a novel, dynamic expression pattern for Vglut2 and an undescribed co-expression domain for Vglut3 in the NA system. In contrast to our initial hypothesis that NA-derived glutamate is required to breathing, our functional studies showed that loss of Vglut2 throughout the NA system failed to alter breathing or metabolism under room air, hypercapnia, or hypoxia in unrestrained and unanesthetized mice. These data demonstrate that Vglut2-based glutamatergic signaling within the central NA system is not required for normal baseline breathing and hypercapnic, hypoxic chemosensory reflexes. These outcomes challenge the current understanding of central NA neurons in the control of breathing and suggests that glutamate may not be a critical target to understand NA neuron dysfunction in respiratory diseases.

Neonatal and Maternal Outcomes in Nulliparous Individuals according to Prepregnancy Body Mass Index.

This study aimed to examine the effect of incremental changes in body mass index (BMI, kg/m2) on the association with adverse pregnancy outcomes. This was a retrospective cohort study of U.S. vital statistics Live Birth and Infant Death linked data from 2011 to 2020. We limited analyses to nulliparas with singleton pregnancies who delivered at 20 weeks or greater. Outcomes were compared according to the prepregnancy BMI category using 5 kg/m2 increments, with each of the other BMI categories sequentially as the referent. The composite neonatal outcome was defined as any neonatal death, neonatal intensive care unit (ICU), surfactant use, ventilation use, or seizure. Severe maternal morbidity was defined as any maternal ICU, transfusion, uterine rupture, and hysterectomy. Adjusted relative risks were calculated for each BMI category as a referent group, using modified Poisson regression and adjusting for confounders. A total of 11,174,890 nulliparous individuals were included. From 2011 to 2020, the proportions of individuals with BMI 40 or greater, BMI 50 or greater, and BMI 60 or greater increased significantly (from 3.1 to 4.9%, from 0.4 to 0.6%, from 0.03 to 0.06%, respectively; all trend p-values < 0.001). As BMI deviated from normal BMI, risks of neonatal and maternal adverse outcomes increased progressively. For example, as BMI deviated from normal BMI (18.5-24.9), the risk of composite neonatal outcome increased by 2% in individuals with BMI < 18.5 and up to 2.11-fold in individuals with BMI 65-69.9. When compared with BMI 40 to 44.9, BMI 35 to 39.9 was associated with an 8% decreased risk of composite neonatal outcome, whereas BMI 45 to 49.9 was associated with an 8% increased risk of composite neonatal outcome. Incremental increases in prepregnancy BMI are linked to higher risks of adverse pregnancy outcomes, highlighting the need for effective weight management before conception. · Incremental BMI increases raise pregnancy risks.. · Higher BMI linked to adverse neonatal outcomes.. · Elevated BMI heightens severe maternal morbidity..

Dimethyl Fumarate Strongly Ameliorates Gray and White Matter Brain Injury and Modulates Glial Activation after Severe Hypoxia-Ischemia in Neonatal Rats.

Neonatal hypoxia-ischemia is a major cause of infant death and disability. The only clinically accepted treatment is therapeutic hypothermia; however, cooling is less effective in the most severely encephalopathic infants. Here, we wanted to test the neuroprotective effect of the antioxidant dimethyl fumarate after severe hypoxia-ischemia in neonatal rats. We used a modified Rice-Vannucci model to generate severe hypoxic-ischemic brain damage in day 7 postnatal rats, which were randomized into four experimental groups: Sham, Sham + DMF, non-treated HI, and HI + DMF. We analyzed brain tissue loss, global and regional (cortex and hippocampus) neuropathological scores, white matter injury, and microglial and astroglial reactivity. Compared to non-treated HI animals, HI + DMF pups showed a reduced brain area loss (p = 0.0031), an improved neuropathological score (p = 0.0016), reduced white matter injuries by preserving myelin tracts (p < 0.001), and diminished astroglial (p < 0.001) and microglial (p < 0.01) activation. After severe hypoxia-ischemia in neonatal rats, DMF induced a strong neuroprotective response, reducing cerebral infarction, gray and white matter damage, and astroglial and microglial activation. Although further molecular studies are needed and its translation to human babies would need to evaluate the molecule in piglets or lambs, DMF may be a potential treatment against neonatal encephalopathy.

NURSING APPROACH IN SPINAL MUSCULAR ATROPHY

Spinal muscular atrophy is an important genetic disease that affects motor neurons in the spine, causing muscle weakness, particularly in infancy. Spinal muscular atrophy occurs with a deletion of the survival motor neuron gene and is one of the leading causes of early death in infants. Although some drugs are used for the treatment of spinal muscular atrophy in the world and in Turkey, there is still no treatment method that provides complete recovery. The limited treatment options for spinal muscular atrophy, its inaccessibility and the poor prognosis of the disease negatively affect the quality of life of individuals and their families. All stages of the disease, starting from the diagnosis process, are very difficult for the patient and his family. A multidisciplinary approach is needed to help patients and their families cope with these difficulties. This approach includes areas such as medical care, rehabilitation, psychosocial support and education. It is essential that nurses, as key members of the health care team, improve the patient's quality of life, manage symptoms and support the individual and family in this process. In particular, supporting the patient and family in their care and educating them about their care needs is one of the most important roles of nurses. With this review, an attempt has been made to discuss the diagnostic methods, treatment process and nursing approaches of spinal muscular atrophy disease, which is a current problem in the world and in Turkey.

Maternal characteristics and infant and child mortality: A cohort study in England linking Census and health data

Child mortality is a common measure of the overall health of society. Maternal characteristics, such as ethnicity and socioeconomic status are known to contribute to inequalities in health and mortality in babies and children. Overall, in the UK babies born to non-white mothers have a higher risk of mortality, and there is also a strong association between deprivation and risk of death. However, population data is currently lacking for England and Wales disentangling the various socioeconomic risk factors which are known to contribute to increased risk. We utilise population level data to assess the association between socioeconomic status, ethnicity, and child mortality. Our cohort consisted of all live singleton births in England and Wales between 2011 and 2016. We linked birth notifications to mothers’ 2011 Census records using NHS number, which provides person-level sociodemographic information. Death registration data was linked to identify all-cause and cause-specific deaths in babies. Babies were followed from date-of-birth for up to 10-years, or date-of-death. We report cumulative incidence of all-cause mortality for a 10-year follow-up for neonatal, infant and child deaths based on maternal socioeconomic and ethnic groups. Cox proportional hazard models are used to estimate hazard ratios for neonatal, infant and child deaths, with both minimally adjusted (maternal age and baby sex) and fully-adjusted models (accounting for other maternal, household and birth characteristics). This presentation will give an overview of our unique linked data sources, the statistical techniques employed, the latest available analytical results, and the emerging implications of the research.

Early Newborn Metabolic Patterning and Sudden Infant Death Syndrome

Sudden infant death syndrome (SIDS) is a major cause of infant death in the US. Previous research suggests that inborn errors of metabolism may contribute to SIDS, yet the relationship between SIDS and biomarkers of metabolism remains unclear. To evaluate and model the association between routinely measured newborn metabolic markers and SIDS in combination with established risk factors for SIDS. This was a case-control study nested within a retrospective cohort using data from the California Office of Statewide Health Planning and Development and the California Department of Public Health. The study population included infants born in California between 2005 and 2011 with full metabolic data collected as part of routine newborn screening (NBS). SIDS cases were matched to controls at a ratio of 1:4 by gestational age and birth weight z score. Matched data were split into training (2/3) and testing (1/3) subsets. Data were analyzed from January 2005 to December 2011. Metabolites measured by NBS and established risk factors for SIDS. The primary outcome was SIDS. Logistic regression was used to evaluate the association between metabolic markers combined with known risk factors and SIDS. Of 2 276 578 eligible infants, 354 SIDS (0.016%) cases (mean [SD] gestational age, 38.3 [2.3] weeks; 220 male [62.1%]) and 1416 controls (mean [SD] gestational age, 38.3 [2.3] weeks; 723 male [51.1%]) were identified. In multivariable analysis, 14 NBS metabolites were significantly associated with SIDS in a univariate analysis: 17-hydroxyprogesterone, alanine, methionine, proline, tyrosine, valine, free carnitine, acetyl-L-carnitine, malonyl carnitine, glutarylcarnitine, lauroyl-L-carnitine, dodecenoylcarnitine, 3-hydroxytetradecanoylcarnitine, and linoleoylcarnitine. The area under the receiver operating characteristic curve for a 14-marker SIDS model, which included 8 metabolites, was 0.75 (95% CI, 0.72-0.79) in the training set and was 0.70 (95% CI, 0.65-0.76) in the test set. Of 32 infants in the test set with model-predicted probability greater than 0.5, a total of 20 (62.5%) had SIDS. These infants had 14.4 times the odds (95% CI, 6.0-34.5) of having SIDS compared with those with a model-predicted probability less than 0.1. Results from this case-control study showed an association between aberrant metabolic analytes at birth and SIDS. These findings suggest that we may be able to identify infants at increased risk for SIDS soon after birth, which could inform further mechanistic research and clinical efforts focused on monitoring and prevention.

Nursery- vs. Mother-Reared Baboons: Reproductive Success and Health Parameters.

There is a plethora of data demonstrating the deleterious consequences of nursery rearing in nonhuman primates (NHPs). However, baboon studies report varying consequences of nursery rearing, from no differences in reproduction and sociality to moderate differences in social cognition and abnormal behavior. We compared health and reproductive parameters in a large sample (N= 231) of mother-reared (MR) and nursery-reared (NR) captive olive baboons housed at the Keeling Center for Comparative Medicine and Research, Texas. MR baboons had higher neutrophil-to-lymphocyte ratios and heart rates than NR baboons. Rearing was not a significant predictor of body condition score or body weight (p > 0.20), and MR and NR individuals did not differ in the level of wounding observed (p > 0.70). The proportion of successful births across NR and MR females was also not significantly different (p > 0.70), nor were rates of maternal neglect and infant death. These data suggest minimal differences in health and reproductive parameters across rearing statuses in baboons housed at this facility. In conjunction with previous research that also seems to show minimal differences as a function of rearing in baboons, but directly contrast with data in other NHP species, these data suggest that baboons may be more robust against deleterious effects of abnormal rearing conditions than other NHP species.

Community partnership approaches to safe sleep (CPASS) program evaluation

BackgroundSudden unexpected infant death (SUID) continues to be a leading cause of death in infants in the United States (US), with significant disparities by race and socio-economic status. Infant safe sleep behaviors are associated with decreasing SUID risk, but challenges remain for families to practice these routinely. The objective of this program was to implement and evaluate a novel approach for an infant safe sleep pilot program built upon partnerships between hospitals and community-based organizations (CBOs) serving pregnant and parenting families in at-risk communities.MethodsCommunity Partnership Approaches to Safe Sleep (CPASS) was a prospectively implemented infant safe sleep program. CPASS included children’s hospitals partnered with CBOs across five US cities: Portland, OR, Little Rock AR, Chicago, IL, Birmingham, AL, and Rochester, NY. The program consisted of (1) monthly learning community calls; (2) distribution of Safe Sleep Survival Kits; and (3) surveys of sites and families regarding program outcomes. Survey measures included (1) site participation in CPASS activities; (2) recipients’ use of Safe Sleep Kits; and (3) recipients’ safe sleep knowledge and behaviors.ResultsCPASS learning community activities were consistently attended by at least two representatives (1 hospital-based, 1 CBO-based) from each site. Across the five sites, 1002 safe kits were distributed over 9 months, the majority (> 85%) to families with infants ≤ 1 month old. Among participating families, 45% reported no safe sleep location before receipt of the kit. Family adherence to nighttime safe sleep recommendations included: (1) no bedsharing (M 6.0, SD 1.8, range 0–7); (2) sleep on back (M 6.3, SD 1.7, range 0–7); and (3) sleep in a crib with no blankets/toys (M 6.0, SD 2.0, range 0–7). Site interviews described how participation in CPASS influenced safe sleep conversations and incorporated local data into counseling. Hospital-CBO relationships were strengthened with program participation.ConclusionsThe CPASS pilot program provides a new, innovative model built on hospital-community partnerships for infant safe sleep promotion in SUID-impacted communities. CPASS reached families before their infant’s peak age risk for SUID and empowered families with knowledge and resources to practice infant safe sleep. Important lessons learned included improved ways to center and communicate with families.

Rates of Sudden Unexpected Infant Death Before and During the COVID-19 Pandemic

Infection has been postulated as a driver in the sudden infant death syndrome (SIDS) cascade. Epidemiologic patterns of infection, including respiratory syncytial virus and influenza, were altered during the COVID-19 pandemic. Comparing month-to-month variation in both sudden unexpected infant death (SUID) and SIDS rates before and during the pandemic offers an opportunity to generate and expand existing hypotheses regarding seasonal infections and SUID and SIDS. To compare prepandemic and intrapandemic rates of SUID and SIDS, assessing for monthly variation. This cross-sectional study assessed US mortality data provided by the Centers for Disease Control and Prevention for January 1, 2018, through December 31, 2021. Events with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for SIDS (R95), unknown (R99), and accidental suffocation and strangulation in bed (W75) causes of death were examined. The data analysis was performed between November 2, 2023, and June 2, 2024. COVID-19 pandemic. The primary and secondary outcomes were the monthly rates of SUID and SIDS during the COVID-19 pandemic (March 1, 2020, to December 31, 2021) compared with the prepandemic period (March 1, 2018, to December 31, 2019) as measured using generalized linear mixed-effects models. Seasonal trends in RSV and influenza rates were also examined. There were 14 308 SUID cases from January 1, 2018, to December 31, 2021 (42% female infants). Compared with the prepandemic period, the risk of SUID increased during the intrapandemic period (intensity ratio [IR], 1.06; 95% CI, 1.05-1.07). Monthly assessments revealed an increased risk of SUID beyond the prepandemic baseline starting in July 2020, with a pronounced epidemiologic shift from June to December 2021 (ranging from 10% to 14%). Rates of SIDS were elevated throughout the intrapandemic period compared with the prepandemic baseline, with the greatest increase in July 2021 (IR, 1.18; 95% CI, 1.13-1.22) and August 2021 (IR, 1.17; 95% CI, 1.13-1.22). Seasonal shifts in RSV hospitalizations correlated with monthly changes in SUID observed during 2021. This cross-sectional study found increased rates of both SUID and SIDS during the COVID-19 pandemic, with a significant shift in epidemiology from the prepandemic period noted in June to December 2021. These findings support the hypothesis that off-season resurgences in endemic infectious pathogens may be associated with SUID rates, with RSV rates in the US closely approximating this shift. Further investigation into the role of infection in SUID and SIDS is needed.

Estimating the stochastic uncertainty underlying sample-based estimates of infant mortality in the Philippines: a first-time application to a country in the Southeast Asia/Pacific Basin region

ABSTRACT Infant mortality is an important population health statistic that is often used to make health policy decisions. Unfortunately, these data are not available for all populations. A newly developed method is presented for accounting for the stochastic uncertainty found in infant mortality rates (IMRs) estimated from sample surveys and for the first time applied to a country in the Southeast Asian/Pacific Basin area, the Philippines. The method is founded on the fact that there are two sources of variation in sample-based estimates of IMRs: (1) sample size; and (2) variation of infant deaths. The approach is aimed at taking into account stochastic uncertainty while preserving information concerning the uncertainty due to sampling. In applying the method to the Philippines, the sample-based IMR estimates appear to perform well in terms of accounting for stochastic uncertainty. This finding is consistent with previous research assessing this approach in Africa and with variations, in Canada, Europe and the United States, which suggests that in the form presented here or in one of its variants, it could successfully be employed not only elsewhere in the Southeast Asia/Pacific Basin region but also in East Asia, North Asia, South Asia, and West Asia.

ANALYSIS OF INFANT MORTALITY IN THE WORKING AREA OF NORTH MUSI RAWAS REGENCY IN 2024

Infant deaths are caused by the top three causes of death, namely LBW, asphyxia and infection. Meanwhile, the highest cause of other neonatal deaths was caused by intrapulmonary complications such as respiratory and cardiovascular disorders. This research aims to determine the picture of infant mortality in the working area of ​​North Musi Rawas Regency in 2024. The design of this research is quantitative with a case control approach. The population in this study were all mothers who gave birth in North Musi Rawas Regency in January 2023. The sample in this study was 99 people, with sampling using case and control 3:1. Namely cases as many as 33 respondents and controls as many as 66 respondents, with the inclusion criteria being willing to become respondents by filling out a consent form, and parents of toddlers. This research was carried out on March 30 - April 29 2024. Primary data was collected by interviews using questionnaires. Bivariate data analysis used the Chi-Square test. The results of the study showed that there was a relationship between birth attendant (p value 0.01), place of delivery (p value 0.002), birth weight (p value 0.006), ANC visits (p value 0.00), and comorbidities (p value 0, 00) with the incidence of infant deaths in the working area of ​​North Musi Rawas Regency in 2024. The most dominant factor in the incidence of infant deaths in the working area of ​​North Musi Rawas Regency in 2024, namely birth weight (p value 0.004) (OR 0.261). The conclusion is that there is a relationship between birth attendants, place of delivery, birth weight, ANC visits and comorbidities. The Health Service should coordinate with the Community Health Center to carry out scheduled posyandu activities.

‘No sword could ever pierce my heart more than when I must miss my child’: Power dynamics, agency and motherhood in the prison of ‘s‐Hertogenbosch 1820–1880

AbstractUsing a microhistorical lens on the prison of ‘s‐Hertogenbosch in the Netherlands, this article focuses on practices and regulations concerning mothers and children and ideas about motherhood and practices of care to show how different powers intersected and were ‘at work’ within the prison. Analysing the decision‐making, discourses and practices the authorities used to exert power over criminalised women and their children, this article argues that the prison policy was not designed to care for or protect mothers and children. On the contrary, it led to the deaths of many infants incarcerated with their mothers. Moreover, it paradoxically deprived incarcerated women of one of the pillars of nineteenth‐century bourgeois femininity: motherhood. The mothers, however, actively resisted and negotiated the prison's power mechanisms to create opportunities to care for their children and influence their fate.

Toilet construction under the Swachh Bharat Mission and infant mortality in India

Improvement of water and sanitation conditions may reduce infant mortality, particularly in countries like India where open defecation is highly prevalent. We conducted a quasi-experimental study to investigate the association between the Swachh Bharat Mission (SBM)—a national sanitation program initiated in 2014—and infant (IMR) and under five mortality rates (U5MR) in India. We analyzed data from thirty-five Indian states and 640 districts spanning 10 years (2011–2020), with IMR and U5MR per thousand live births as the outcomes. Our main exposure was the district-level annual percentage of households that received a constructed toilet under SBM. We mapped changes in IMR and U5MR and toilet access at the district level over time. We fit two-way fixed effects regression models controlling for sociodemographic, wealth, and healthcare-related confounders at the district-level to estimate the association between toilets constructed and child mortality. Toilet access and child mortality have a historically robust inverse association in India. Toilets constructed increased dramatically across India following the implementation of SBM in 2014. Results from panel data regression models show that districts with > 30% toilets constructed under SBM corresponds with 5.3 lower IMR (p < 0.05), and 6.8 lower U5MR (p < 0.05). Placebo, falsification tests and robustness checks support our main findings. The post-SBM period in India exhibited accelerated reductions in infant and child mortality compared to the pre-SBM years. Based on our regression estimates, the provision of toilets at-scale may have contributed to averting approximately 60,000–70,000 infant deaths annually. Our findings show that the implementation of transformative sanitation programs can deliver population health benefits in low- and middle-income countries.

Safety of quadrivalent recombinant influenza vaccine in pregnant persons and their infants

BackgroundThe Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists (ACOG) recommend that all pregnant persons receive any licensed, recommended, and age-appropriate inactivated influenza vaccine (SD-IIV) or recombinant influenza vaccine (RIV) to protect against influenza and influenza-related complications. RIV was safe and efficacious in pre- and postlicensure studies, however there is limited RIV safety data in pregnant persons. ObjectiveTo evaluate the safety of quadrivalent recombinant influenza vaccine (RIV4) versus a quadrivalent standard-dose, inactivated influenza (SD-IIV4) in a large cohort of pregnant persons and their infants. Study DesignThis postlicensure observational safety study conducted at Kaiser Permanente Northern California evaluated the subset of pregnant persons vaccinated in routine care as part of a larger cluster-randomized vaccine effectiveness study comparing RIV4 vs. SD-IIV4 (ClinicalTrials.gov NCT03694392). We identified pregnancy (spontaneous abortion, preterm labor, stillbirth/fetal death, congenital/fetal anomalies detected during pregnancy, eclampsia/pre-eclampsia, placental abruption), birth (preterm birth, low birth weight, small for gestational age), and neonatal/infant outcomes (infant death, failure to thrive, congenital anomalies detected after delivery) using diagnostic codes among pregnant persons ≥18 years immunized with RIV4 or SD-IIV4 during the 2018/19 and 2019/20 influenza seasons and their infants. We used conditional logistic regression adjusted for age group, race, ethnicity, trimester of influenza vaccination, comorbidities, and BMI, stratified by gestational age to estimate the odds ratio (OR) of pregnancy outcomes following vaccination with RIV4 vs. SD-IIV4. Using logistic regression, we separately estimated the adjusted OR of birth and neonatal/infant outcomes in the first year of life (eg, death) in infants of RIV4 vs. SD-IIV4 vaccinated pregnant persons. ResultsThe study population included 48,781 pregnant persons (RIV4 = 14,981; SD-IIV4 = 33,800) and 47,394 live births (RIV4 = 14,538; SD-IIV4 = 32,856). There was no statistical difference in any pregnancy outcome or in birth and neonatal/infant outcome between RIV4 vs. SD-IIV4 vaccinated pregnant persons and their infants. ConclusionCompared with receipt of a SD-IIV4 during pregnancy, this large study did not identify any pregnancy, birth, or neonatal/infant safety concerns following receipt of a RIV4 during pregnancy and demonstrates that the safety of RIV4 in pregnancy was similar to SD-IIV4. This study provides additional evidence regarding the safety of influenza vaccination in pregnant persons and further supports ACIP and ACOG recommendations that all pregnant persons receive an inactivated or recombinant influenza vaccine.

Perinatal outcomes according to umbilical artery Doppler assessment among fetuses with congenital heart disease.

To evaluate a cohort of fetuses with congenital heart disease (CHD) who underwent serial umbilical artery (UA) Doppler surveillance and assess perinatal outcome according to UA Doppler assessment. A retrospective cohort study of singleton fetuses with CHD at a single academic center was performed between 2018 and 2020. Fetuses with a chromosomal abnormality or growth restriction were excluded. We compared fetuses with normal versus abnormal UA Doppler assessment at any time in pregnancy. Abnormal UA Doppler assessment was defined as decreased end diastolic flow, determined by an elevated systolic/diastolic ratio >95th percentile for gestational age, or absent/reversed end diastolic flow. Logistic regression assessed the odds of fetuses with CHD and abnormal UA Doppler assessment having a composite adverse perinatal (defined as fetal, neonatal, or infant death), adjusting for relevant covariates. We identified a cohort of 171 fetuses with CHD that met inclusion criteria. Of these, 154 (90%) had normal UA Doppler assessment and 17 (10%) had abnormal UA Doppler assessment throughout pregnancy. Maternal characteristics did not differ between groups except for maternal race and history of preeclampsia. There was no statistically significant difference in primary outcome between groups [14% (21/154) of fetuses with normal UA Doppler assessment had an adverse perinatal outcome compared to 24% (4/17) of those with abnormal UA Doppler assessment, p = 0.28]. UA Doppler assessment is unlikely to predict adverse perinatal outcome in normally grown, euploid singleton fetuses with CHD.

Machine-learning-based evaluation of the usefulness of lactate for predicting neonatal mortality in preterm infants

BackgroundUnlike in adult and pediatric patients, the usefulness of lactate in preterm infants has not been thoroughly discussed. This study aimed to evaluate whether the lactate level in the first hours of life is an important factor associated with neonatal death in very-low-birth-weight (VLBW) preterm infants. MethodsElectronic medical records from a level 4 neonatal intensive care unit in South Korea were reviewed to obtain perinatal and neonatal outcomes. Data on lactate levels of preterm infants in the first 12 h of life were collected. Neonatal mortality and morbidities were compared based on lactate levels. Subsequently, machine-learning models incorporating 20 independent variables, both with and without lactate, were compared for model performances and feature importance of lactate for predicting in-hospital mortality in the applicable models. ResultsOne hundred and sixty-eight preterm infants were included. Death rates on days 7 and 30 of life (D30-mortality) were significantly higher in infants with high lactate levels (≥3rd interquartile range) than in those with lower levels (<3rd interquartile range). Though statistically insignificant, the overall in-hospital mortality was more than twice as high in the high lactate level group than in the lower lactate level group. Based on the machine learning results, Random Forest, Gradient Boosting, and LightGBM models all showed greater area under the curves when lactate was included. Lactate consistently ranked in the variables of top five feature importance, particularly showing the greatest value in the Gradient Boosting model. ConclusionLactate levels during the early hours of life may be an important factor associated with in-hospital death of preterm VLBW infants. Based on the enhanced performance of the above-mentioned machine learning models, lactate levels in the early postnatal period may add to assessing the clinical status and predicting the hospital course in this population.