Genetic disorders and their association with morbidity and mortality in early preterm small for gestational age infants.

BACKGROUND: Early preterm (<34 weeks of gestation) small for gestational age infants (<10th percentile birth weight for sex and gestational age) experience high rates of morbidity and mortality, the causes of which are poorly understood. Mounting evidence suggests that genetic disorders contribute. Scarce data exist regarding the prevalence of genetic disorders and their contribution to morbidity and mortality. OBJECTIVE: This study aimed to determine the proportion of genetic disorders in early preterm small for gestational age infants (with and without congenital anomalies) compared to early preterm appropriate for gestational age infants and the association of genetic disorders with morbidity or mortality. STUDY DESIGN: This is a retrospective cohort study of infants delivered at 23 and 0/7 to 33 and 6/7 weeks of gestation from 2000 to 2020 from the Pediatrix Clinical Data Warehouse. Data included diagnosed genetic disorders and congenital anomalies, baseline characteristics, and morbidity or mortality. We excluded cases of death in the delivery room before neonatal intensive care unit admission, multiple gestations, and cases transferred after birth or before death or discharge. RESULTS: We identified 223,431 early preterm infants, including 21,180 small for gestational age. Genetic disorders were present in 441 (2.3%) of small for gestational age infants without congenital anomalies, in 194 (10.8%) of small for gestational age infants with congenital anomalies, and in 304 (4.5%) of small for gestational age infants that experienced morbidity or mortality (with or without congenital anomalies). Trisomies 13, 18, and 21 were the most prevalent genetic disorders in these groups, together accounting for 145 small for gestational age infants without congenital anomalies, 117 small for gestational age infants with congenital anomalies, and 166 small for gestational age infants with morbidity or mortality (with or without congenital anomalies). Less prevalent genetic disorders consisted of other aneuploidy (45, X and 47, XXY), copy number variants (13q14 deletion syndrome, cri du chat syndrome, DiGeorge syndrome), and single gene disorders (cystic fibrosis, Fanconi anemia, glucose-6-phosphate dehydrogenase deficiency, hemophilia, hypophosphatasia, sickle cell disease, and thalassemia). Comparatively, genetic disorders were found in 1792 (1.0%) appropriate for gestational age infants without congenital anomalies, in 572 (5.8%) appropriate for gestational age infants with congenital anomalies, and 809 (2.0%) appropriate for gestational age infants that experienced morbidity or mortality (with or without congenital anomalies). Genetic disorders were associated with an adjusted odds ratio (95% confidence interval) of 2.10 (1.89-2.33) of isolated small for gestational age and 12.84 (11.47-14.35) of small for gestational age accompanied by congenital anomalies. Genetic disorders were associated with an adjusted odds ratio of 2.24 (1.83-2.74) of morbidity or mortality. CONCLUSION: These findings suggest that genetic disorders are more prevalent in early preterm small for gestational age infants, particularly those with congenital anomalies. These findings also suggest that genetic disorders are associated with increased morbidity and mortality. These associations were primarily driven by trisomies 13, 18, and 21. Genetic diagnoses in this cohort were made through routine clinical care, principally via karyotype, chromosomal microarray, and single gene testing. These findings support evolving clinical guidelines for genetic testing of small for gestational age infants. Our study is limited due to the lack of prospective, genome-wide testing.

Prenatal vs postnatal diagnosis of 22q11.2 deletion syndrome: cardiac and noncardiac outcomes through 1 year of age.

BACKGROUND: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis. OBJECTIVE: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome. STUDY DESIGN: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 deletion syndrome by 1 year of age with or without congenital heart disease; those with prenatal diagnosis or suspicion (suggestive ultrasound findings and/or high-risk cell-free fetal DNA screen for 22q11.2 deletion syndrome with postnatal confirmation) were compared with those with postnatal diagnosis. Perinatal management, cardiac and noncardiac morbidity, and mortality by 1 year were assessed. Outcomes were adjusted for presence of critical congenital heart disease, gestational age at birth, and site. RESULTS: A total of 625 fetuses, neonates, or infants with 22q11.2 deletion syndrome (53.4% male) were included: 259 fetuses were prenatally diagnosed (156 [60.2%] were live-born) and 122 neonates were prenatally suspected with postnatal confirmation, whereas 244 infants were postnatally diagnosed. In the live-born cohort (n=522), 1-year mortality was 5.9%, which did not differ between groups but differed by the presence of critical congenital heart disease (hazard ratio, 4.18; 95% confidence interval, 1.56-11.18; P<.001) and gestational age at birth (hazard ratio, 0.78 per week; 95% confidence interval, 0.69-0.89; P<.001). Adjusting for critical congenital heart disease and gestational age at birth, the prenatal cohort was less likely to deliver at a local community hospital (5.1% vs 38.2%; odds ratio, 0.11; 95% confidence interval, 0.06-0.23; P<.001), experience neonatal cardiac decompensation (1.3% vs 5.0%; odds ratio, 0.11; 95% confidence interval, 0.03-0.49; P=.004), or have failure to thrive by 1 year (43.4% vs 50.3%; odds ratio, 0.58; 95% confidence interval, 0.36-0.91; P=.019). CONCLUSION: Prenatal detection of 22q11.2 deletion syndrome was associated with improved delivery management and less cardiac and noncardiac morbidity, but not mortality, compared with postnatal detection.

Effect of maternal vaccination on infant morbidity in Bangladesh.

BACKGROUND: Risk factors of infant mortality in Africa and south Asian countries have been broadly discussed. However, infant morbidity is largely underestimated. We analyzed the data from a randomized vaccine trial in Bangladesh to identify and assess the effect of risk factors on infant morbidity. METHODS: Pregnant women were randomly assigned to receive either inactivated influenza vaccine or pneumococcal polysaccharide vaccine and the infants were randomly assigned to receive 7-valent pneumococcal conjugate vaccine or Hib conjugate vaccine at week 6, 10 and 14. The data were collected from August 2004 through December 2005. Each pair of infant and mother were followed for 24 weeks after birth with weekly visits. Generalized estimating equations (GEE) for repeated measurements and Poisson regression models were used to identify the risk factors and evaluate their effect on the longitudinal incidence and total number of episodes of respiratory illness with fever (RIF), diarrhea disease, ear problem and pneumonia. RESULTS: A total of 340 pregnant women were randomized with mean age of 25 years. The baseline mother and infant characteristics were similar between two treatment groups. Exclusive breastfeeding and higher paternal education level were common factors associated with lower infant morbidity of RIF (adjusted OR = 0.40 and 0.94 with p < 0.01 and p = 0.02, respectively), diarrhea disease (adjusted OR = 0.39 and 0.95 with p < 0.01 and p = 0.04, respectively), and ear problem (adjusted OR = 0.20 and 0.76 with p < 0.01 and p < 0.01, respectively). Maternal influenza vaccine significantly reduced the incidence of RIF (adjusted OR = 0.54; p < 0.01) but not diarrhea disease or ear problem (p > 0.05). Female infants had lower incidence of diarrhea disease (adjusted OR = 0.67; p = 0.01) and ear problem (adjusted OR = 0.12; p = 0.01). CONCLUSIONS: Maternal influenza vaccination, exclusive breastfeeding, female children, and higher paternal education level significantly reduced the infant morbidity within the 24 weeks after birth in Bangladesh.

The role of the placenta in perinatal asphyxia, neonatal encephalopathy, and neurodevelopmental outcome: A review.

Perinatal asphyxia contributes significantly to neonatal deaths globally. This may occur due to the effects of various phenomena like uterine rupture, infections, maternal hemodynamic compromise (amniotic fluid embolus), placenta, and umbilical cord (umbilical cord knot, placental abruption, or compression). Perinatal asphyxia is the term used for interrupted blood flow or the exchange of gases in the fetus during the prenatal period. The reduced oxygenation induces a cascade of brain injuries, resulting in long-term damage to the infant's brain. Some infants exposed to perinatal hypoxia-ischemia will make an immediate recovery and have normal survival, while others may suffer from an evolving clinical encephalopathy. This review article focuses on the relationship between the placenta, neonatal encephalopathy, and neurodevelopmental outcome. It also aims to identify possible interventions and drive the focus of policymakers towards issues that evolve around perinatal asphyxia, neonatal encephalopathy, and neonatal care and that have a high impact on infant morbidity in sub-Saharan Africa.

Adverse Maternal Fetal Environment Partially Mediates Disparate Outcomes in Non-White Neonates with Major Congenital Heart Disease.

OBJECTIVE: To determine whether differential exposure to an adverse maternal fetal environment partially explains disparate outcomes in infants with major congenital heart disease (CHD). STUDY DESIGN: Retrospective cohort study utilizing a population-based administrative California database (2011-2017). Primary exposure: Race/ethnicity. Primary mediator: Adverse maternal fetal environment (evidence of maternal metabolic syndrome and/or maternal placental syndrome). OUTCOMES: Composite of 1-year mortality or severe morbidity and days alive out of hospital in the first year of life (DAOOH). Mediation analyses determined the percent contributions of mediators on pathways between race/ethnicity and outcomes after adjusting for CHD severity. RESULTS: Included were 2747 non-Hispanic White infants (reference group), 5244 Hispanic, and 625 non-Hispanic Black infants. Hispanic and non-Hispanic Black infants had a higher risk for composite outcome (crude OR: 1.18; crude OR: 1.25, respectively) and fewer DAOOH (-6 & -12 days, respectively). Compared with the reference group, Hispanic infants had higher maternal metabolic syndrome exposure (43% vs 28%, OR: 1.89), and non-Hispanic Black infants had higher maternal metabolic syndrome (44% vs 28%; OR: 1.97) and maternal placental syndrome exposure (18% vs 12%; OR, 1.66). Both maternal metabolic syndrome exposure (OR: 1.21) and maternal placental syndrome exposure (OR: 1.56) were related to composite outcome and fewer DAOOH (-25 & -16 days, respectively). Adverse maternal fetal environment explained 25% of the disparate relationship between non-Hispanic Black race and composite outcome and 18% of the disparate relationship between Hispanic ethnicity and composite outcome. Adverse maternal fetal environment explained 16% (non-Hispanic Black race) and 21% (Hispanic ethnicity) of the association with DAOOH. CONCLUSIONS: Increased exposure to adverse maternal fetal environment contributes to racial and ethnic disparities in major CHD outcomes.

Supplementation with Small-Quantity Lipid-Based Nutrient Supplements Does Not Increase Child Morbidity in a Semiurban Setting in Ghana: A Secondary Outcome Noninferiority Analysis of the International Lipid-Based Nutrient Supplements (iLiNS)-DYAD Randomized Controlled Trial.

BACKGROUND: Adequate knowledge about the safety of consumption of small-quantity lipid-based nutrient supplements (SQ-LNSs) is needed. OBJECTIVE: We aimed to test the hypothesis that SQ-LNS consumption is noninferior to control with respect to child morbidity. METHODS: Women (n = 1320) ≤20 wk pregnant were assigned to iron and folic acid until delivery with no supplementation for offspring; or multiple micronutrient supplements until 6 mo postpartum with no supplementation for offspring; or SQ-LNSs until 6 mo postpartum, and SQ-LNSs for offspring (6 mg Fe/d) from 6 to 18 mo of age [the lipid-based nutrient supplement (LNS) group]. We assessed noninferiority (margin ≤20%) between any 2 groups during 0-6 mo of age, and between the non-LNS and LNS groups during 6-18 mo of age for caregiver-reported acute respiratory infection, diarrhea, gastroenteritis, fever/suspected malaria, poor appetite, and "other illnesses." RESULTS: During 0-6 mo of age, 1197 infants contributed 190,503 infant-days. For all morbidity combined, overall mean incidence (per 100 infant-days) was 3.3 episodes, overall mean prevalence (percentage of infant-days) was 19.3%, and the 95% CIs of the incidence rate ratio (IRR) and longitudinal prevalence rate ratio (LPRR) between any 2 groups were ≤1.20. During 6-18 mo, there were 240,097 infant-days for the non-LNS group and 118,698 for the LNS group. For all morbidity combined, group mean incidences were 4.3 and 4.3, respectively (IRR: 1.0; 95% CI: 1.0, 1.1), and mean prevalences were 28.2% and 29.3%, respectively (LPRR: 1.0; 95% CI: 1.0, 1.1). Noninferiority was inconclusive for diarrhea, fever/suspected malaria, and poor appetite. CONCLUSIONS: SQ-LNS consumption does not increase reported overall child morbidity in this population compared with the 2 other treatments.This trial was registered at clinicaltrials.gov as NCT00970866.

Embracing the complexity of modifiable risk reduction: A registry of modifiable risks for 0-12 month infants.

Despite relatively high medical expenditures, the United States performs poorly on population health indicators relative to many other countries. A key step in addressing this situation involves determining impactful and cost-effective interventions for at-risk populations. This requires an understanding of medical, social, behavioral health and safety domains of risk. Of immediate interest are those risks that are modifiable at the individual and family levels and could be reduced through intervention and broader care coordination efforts. Unfortunately, a comprehensive list of such risks does not exist in the published literature. Using multiple interrelated methods, including clinical, social, and care coordination experience, expert elaboration and validation, and reviews of existing assessments and literature, we present what we believe to be the most comprehensive listing of individually modifiable risk factors (IMRFs), relevant to care coordination, available for individuals aged 0-12 months. The list addresses IMRFs within four broad domains of risk (medical, social, behavioral health, and safety). Comprehensive risk registries such as the one presented here can enhance our collective efforts to identify and mitigate risks for specific populations. Such registries can also support research to build understandings of the impact of risks, individually and in interconnected signature combinations. The risk registry presented here and the enhanced understandings flowing from it may yield useful insights for clinicians, social service providers and researchers seeking a whole person approach to care, as well as for payers and policymakers seeking to enable health policy and payment reforms to improve population health.

Risk of prematurity and infant morbidity and mortality by maternal fertility status and plurality.

PURPOSE: To evaluate the risk of prematurity and infant mortality by maternal fertility status, and for in vitro fertilization (IVF) pregnancies, by oocyte source and embryo state combinations. METHODS: Women in 14 States who had IVF-conceived live births during 2004-13 were linked to their infant's birth and death certificates; a 10:1 sample of non-IVF births was selected for comparison; those with an indication of infertility treatment on the birth certificate were categorized as subfertile, all others were categorized as fertile. Risks were modeled separately for the fertile/subfertile/IVF (autologous-fresh only) group and for the IVF group by oocyte source-embryo state combinations, using logistic regression, and reported as adjusted odds ratios (AORs) and 95% confidence intervals (CI). RESULTS: The study population included 2,474,195 pregnancies. Placental complications (placenta previa, abruptio placenta, and other excessive bleeding) and prematurity were both increased with pregestational and gestational diabetes and hypertension, among subfertile and IVF groups, and in IVF pregnancies using donor oocytes. Both subfertile and IVF pregnancies were at risk for prematurity and NICU admission; IVF infants were also at risk for small-for-gestation birthweight, and subfertile infants had greater risks for neonatal and infant death. Within the IVF group, pregnancies with donor oocytes and/or thawed embryos were at greater risk of large-for-gestation birthweight, and pregnancies with thawed embryos were at greater risk of neonatal and infant death. CONCLUSIONS: Prematurity was associated with placental complications, diabetes and hypertension, subfertility and IVF groups, and in IVF pregnancies, donor oocytes and/or thawed embryos.

Outcome of extremely preterm infants after iatrogenic or spontaneous birth.

INTRODUCTION: The risks of preterm birth are known. We investigated the perinatal and infant mortality and morbidity after iatrogenic or spontaneous onset of extremely preterm birth. MATERIAL AND METHODS: The present study used data from the population-based EXPRESS study comprising all infants delivered before 27+0 gestational weeks in Sweden between 2004 and 2007. All fetuses alive at admission and with known mode of onset of delivery were included (682 live-born infants; 65 intrapartum deaths). Four multivariate regression models were applied with adjustments for gestational age, fetal gender, multiple pregnancy, and birthweight. RESULTS: After adjustment for gestational age, no significant differences were found between iatrogenic and spontaneous onsets of birth regarding intrapartum death, early neonatal death (0-6 d), or death within 364 days. In the group with iatrogenic onset of delivery, there was an increased risk for severe morbidity (odds ratio [OR] 1.86, 95% confidence interval [95% CI] 1.15-3.02), severe bronchopulmonary dysplasia (OR 1.90, 95% CI 1.10-3.26), and retinopathy of prematurity (OR 1.99, 95% CI 1.21-3.27) after adjustment for gestational age, fetal gender, and multiple pregnancy. After additional adjustment for weight z-scores at 36 gestational weeks, the associations were not significant. Within the group with spontaneous onset of delivery, fetuses with preterm prelabor rupture of membranes had increased mortality risk. CONCLUSIONS: No evidence was found for mode of onset of delivery (iatrogenic vs spontaneous) having an impact on neonatal or infant mortality or morbidity in extremely preterm infants. Instead, gestational age and growth deviation at birth seem to be associated with the outcome.

The Effect of Level of Care on Gastroschisis Outcomes.

OBJECTIVE: To examine the relationship between level of care in neonatal intensive care units (NICUs) and outcomes for newborns with gastroschisis. STUDY DESIGN: A retrospective cohort study was conducted at 130 California Perinatal Quality Care Collaborative NICUs from 2008 to 2014. All gastroschisis births were examined according to American Academy of Pediatrics NICU level of care at the birth hospital. Multivariate analyses examined odds of mortality, duration of mechanical ventilation, and duration of stay. RESULTS: For 1588 newborns with gastroschisis, the adjusted odds of death were higher for those born into a center with a level IIA/B NICU (OR, 6.66; P = .004), a level IIIA NICU (OR, 5.95; P = .008), or a level IIIB NICU (OR, 5.85; P = .002), when compared with level IIIC centers. The odds of having more days on ventilation were significantly higher for births at IIA/B and IIIB centers (OR, 2.05 [P < .001] and OR, 1.91 [P < .001], respectively). The odds of having longer duration of stay were significantly higher at IIA/B and IIIB centers (OR, 1.71 [P < .004]; OR, 1.77 [P < .001]). CONCLUSIONS: NICU level of care was associated with significant disparities in odds of mortality for newborns with gastroschisis.

Incidence of apparent life-threatening events and post-neonatal risk factors.

AIM: Even though a standard clinical definition for an apparent life-threatening event (ALTE) was established more than two decades ago, the specific International Classification of Disease (ICD) code was firstly included only in 2012. This study estimated the incidence of ALTEs in Northern Italy, together with features and risk factors. METHODS: We used the Lombardy Region Hospital Discharge Records (HDR) database to estimate the cumulative incidence for ALTE during 2002-2006 and drew up a risk profile by comparing cases with and without ALTE who were followed in infancy. RESULTS: There were 246 infants registered in the HDR with ALTE putative diagnostic codes, suggesting a cumulative incidence of 4.1 per 1000 live births in the study area. Of the 148 cases with clinical co-morbidities, 31% had gastroesophageal reflux and 7% had acute respiratory infections. We analysed follow-up data from 15 ALTE cases and 1619 healthy infants and found that the significant risk factors were gastroesophageal reflux and a family history of sudden death. CONCLUSION: We established the regional incidence of ALTE and found risk factors in infants considered healthy in the first week of life and without pathological perinatal conditions. The systematic use of the specific ALTE ICD code (R68.13, ICD-10-CM) and common knowledge about ALTE diagnostic guidelines are clearly needed.

Implications of Using a Fetuses-at-Risk Approach When Fetuses Are Not at Risk.

BACKGROUND: Gestational-age-specific rates of postnatal endpoints are sometimes estimated with denominators based on fetuses-at-risk (FAR), rather than live births. However, as infants can only be included in the numerator after they are born alive, interpretation of such rates is problematic. METHODS: Using simple algebra it can be shown that, at each gestational week, FAR rates of postnatal endpoints are the product of the conventional risk of outcome among live births and the probability of live birth, which increases from near zero early in gestation to close to one in the final weeks. The consequences of such a pattern of live birth on FAR rates are further illustrated in hypothetical scenarios with known conditions. RESULTS: FAR rates of postnatal endpoints will generally increase towards the end of pregnancy due to the rising probability of live birth, regardless of the 'true' effect of immaturity on risk. In the presence of an exposure that increases the probability of early birth, the same mechanism will cause FAR rates to be higher in the exposed group, even if the exposure has no effect. CONCLUSIONS: Gestational-age-specific FAR rates of postnatal outcomes strongly depend on the probability of live birth. Thus, they reflect neither the causal effect of gestational length, nor that of a given exposure. Indeed, if an exposure shortens gestation, FAR rates will be higher in exposed infants even when the exposure has no impact on the outcome under study. These intrinsic limitations should be taken into account when applying FAR analyses to postnatal endpoints.

Family Violence and Maltreatment of Women During the Perinatal Period: Associations with Infant Morbidity in Indian Slum Communities.

OBJECTIVES: To determine the prevalence of non-violent, gender-based forms of maltreatment of women by husbands and in-laws [i.e., gender-based household maltreatment (GBHM)] during pregnancy and postpartum; to clarify the role of GBHM in compromising infant health, and whether this role extends beyond that previously observed for intimate partner violence (IPV). METHODS: Cross-sectional, quantitative data were collected from women (ages 15-35) seeking immunizations for their infants <6 months of age (N = 1061) in urban health centers in Mumbai, India. Logistic regression models were constructed to assess associations between maternal abuse (perinatal IPV, in-law violence and GBHM) and recent infant morbidity (diarrhea, respiratory distress, fever, colic and vomiting). RESULTS: More than one in four women (28.4%) reported IPV during their recent pregnancy and/or during the postpartum period, 2.6% reported perinatal violence from in-laws, and 49.0% reported one or more forms of perinatal GBHM. In adjusted regression models that included all forms of family violence and maltreatment, perinatal GBHM remained significantly associated with infant morbidity (AORs 1.4-1.9); perinatal IPV and in-law violence ceased to predict infant morbidity in models including GBHM. CONCLUSIONS: Findings indicate that non-violent expressions of gender inequity (e.g., nutritional deprivation, deprivation of sleep, blocking access to health care during pregnancy) are more strongly associated with poor infant health than physical or sexual violence from husbands or in-laws in urban India. These results strongly suggest the need to expand the conception of gender inequities beyond IPV to include non-violent forms of gendered mistreatment in considering their impact on infant health.

Experiences with maternal and perinatal death reviews in the UK--the MBRRACE-UK programme.

Established in 1952, the programme of surveillance and Confidential Enquiries into Maternal Deaths in the UK is the longest running such programme worldwide. Although more recently instituted, surveillance and confidential enquiries into perinatal deaths are also now well established nationally. Recent changes to funding and commissioning of the Enquiries have enabled both a reinvigoration of the processes and improvements to the methodology with an increased frequency of future reporting. Close engagement with stakeholders and a regulator requirement for doctors to participate have both supported the impetus for involvement of all professionals leading to greater potential for improved quality of care for women and babies.

Estimating benchmark exposure for air particulate matter using latent class models.

We performed benchmark exposure (BME) calculations for particulate matter when multiple dichotomous outcome variables are involved using latent class modeling techniques and generated separate results for both the extra risk and additional risk. The use of latent class models in this study is advantageous because it combined several outcomes into just two classes (namely, a high-risk class and a low-risk class) and compared these two classes to obtain the BME levels. This novel approach addresses a key problem in risk estimation--namely, the multiple comparisons problem, where separate regression models are fitted for each outcome variable and the reference exposure will rely on the results of the best-fitting model. Because of the complex nature of the estimation process, the bootstrap approach was used to estimate the reference exposure level, thereby reducing uncertainty in the obtained values. The methodology developed in this article was applied to environmental data by identifying unmeasured class membership (e.g., morbidity vs. no morbidity class) among infants in utero using observed characteristics that included low birth weight, preterm birth, and small for gestational age.

Causes of infant and under-five (under-5) morbidity and mortality among hospitalized patients in Southern Nigeria: A hospital based study.

Background: Rate and pattern of under-five mortality is a reflection of a society's healthcare system and quality of life. This study is aimed at reviewing the causes of infants and under-five morbidity and mortality in Calabar, Southern Nigeria. Methods: This study used retrospective descriptive cross-sectional design. We did a retrospective collation of data on under-five morbidity and mortality from 2012 to 2017 of under-five patients admitted or died while in admission in University of Calabar Teaching Hospital. The causes of morbidity and mortality were reported based on International Classification of Diseases 10 (ICD-10). The morbidity, mortality and fatality rates were computed. Results: A total of 11,416 under-five admissions and 391 deaths were recorded within the study period giving a fatality rate of 3.4%. Age 1-4 years category represented 50.5% of the admissions while infants (<1 year) constitute majority of the deaths (64.7%). There were 5652 infant admissions and 253 infant deaths giving fatality rate of 4.5% within the study period. Males constituted majority (55.8%) of under-five morbidity whereas females constituted majority (51.2%) of the deaths. Conditions originating from perinatal period; and infectious and parasitic diseases were the leading broad cause of under-five mortality. Specific disease analysis showed sepsis/septicemia; congenital infectious and parasitic diseases; slow fetal growth, malnutrition and short gestation as the chief causes of both infant and under-five mortality. Conclusion: The leading causes of under-five deaths in the studied population are amenable. Improved healthcare and antenatal will be of immense benefit.

Feasibility Study of a Powder-Based Supplement Intervention for a future Synbiotic Trial in Breastfed Children from South Africa.

Background: Children who are HIV-exposed uninfected (HEU), i.e., born to mothers living with HIV despite not acquiring HIV infection themselves, have increased morbidity and mortality. Data suggests that the breastmilk profile, and more specifically human milk oligosaccharide (HMO) composition, differ by maternal HIV status and may partly help explain this increased risk. We are currently conducting an HMO-based synbiotic randomized trial in breastfed children HEU, the MIGH-T MO study (ClinicalTrials.gov Identifier: NCT05282485), to assess the impact on health outcomes of children HEU. Here, we report our experience from a study of the feasibility and acceptability of a powder-based intervention given to breastfeeding children, conducted prior to the initiation of MIGH-T MO. Methods: 10 mothers living with HIV and their breastfeeding children HEU accessing care at Tygerberg Hospital, in Cape Town, South Africa were enrolled. A powder-based product, potato maltodextrin, was mixed with expressed breast milk and administered to the infants daily for 4 weeks. Data on feasibility, acceptability, adherence, and health outcomes were assessed at the enrollment visit and at the 4 week visit, along with weekly telephone calls. Results: 10 mother-infant pairs were enrolled in this study, with infant age ranging from 6-20 months of age. Among the mothers who met the eligibility criteria, all of them enrolled into the study suggesting high acceptability. While there was some Ioss-to-follow-up after the first visit, among the mothers who remained, there were no major feasibility concerns related to study procedures, product administration, adherence, tolerance, and health outcome assessment. Conclusion: Our pilot study demonstrated that a powder-based intervention for breastfeeding children HEU in South Africa is acceptable and feasible. This suggests potential feasibility and acceptability for other larger studies, including our ongoing MIGH-T MO study, that use similar powder-based interventions such as probiotics, prebiotics, or synbiotics, in breastfed infants from similar settings.

Prenatal cannabis use disorder and infant hospitalization and death in the first year of life.

OBJECTIVE: To determine whether maternal cannabis use disorder is associated with infant hospitalization or death in the first year of life. METHODS: We queried an administrative birth cohort derived from the hospital discharge database maintained by the California Office of Statewide Health Planning and Development and linked with vital statistics files. We included singleton, live-birth deliveries between 2011 and 2018. Pregnancies with cannabis use disorder were classified from International Classification of Disease codes. Outcomes included infant emergency department visits and hospital admissions identified from health records, and infant deaths identified from death records. Models were adjusted for sociodemographic variables, psychiatric comorbidities and other substance use disorders. RESULTS: There were 34,544 births (1.0 %) with a cannabis use disorder diagnosis in pregnancy, with increasing prevalence over the study period. The incidence of infant death in the first year of life was greater among those with a maternal cannabis use disorder diagnosis than those without (1.0 % vs 0.4 %; adjusted risk ratio 1.4 95 % CI: 1.2-1.6). When examining specific causes of death, the increased risk estimates were attributable to perinatal conditions and sudden unexpected infant death. After adjustment, there was no increased risk of infant hospitalizations or emergency department visits. CONCLUSIONS: These findings warrant further investigation into the underlying mechanisms of maternal prenatal CUD on infant outcomes, and add to a rapidly expanding body of literature supporting the need for effective treatment options for pregnant individuals with cannabis use disorders.

Activating Life Course Theory through a Whole System Prevention Framework to Address the Wicked Problem of Maternal and Infant Morbidity and Mortality.

BACKGROUND: Racial/ethnic disparities in maternal and infant morbidity and mortality (MIM&M) is a wicked problem that is reinforced and perpetuated by our system[s] of care. Life Course Theory (LCT) helps to explain drivers of health disparities, but its application is challenged. An upstream approach that promotes systemic change requires the implementation of an expanded prevention framework that includes primordial and quaternary prevention. RESEARCH DESIGN: We developed an innovative expanded Whole System Prevention Framework (WSPF) that incorporates LCT, prevention (including primordial and quaternary prevention) and systems thinking. STUDY SAMPLE: We implemented this new conceptual Framework with two Healthy Start community partnerships through training, service mapping, and strategic planning to address upstream drivers of MIM&M. DATA COLLECTION AND ANALYSIS: Service mapping revealed few Healthy Start upstream activities/services with the predominance being delivered downstream at the program (microsystem) level. RESULTS: Service mapping provided a snapshot of the current service distribution of services across the systems. The preponderance were primary, secondary and tertiary prevention activities (75.5% and 65.6%) delivered at the program level (58.2% and 68%), revealing opportunities for upstream strategies to promote equity. The implementation process provided a new way to frame strategic planning and develop upstream strategies to promote health equity and reduce MIM&M. CONCLUSION: The Whole System Prevention Framework and its implementation methodology could be applied to address other wicked problems.

Influence of single nucleotide polymorphisms (SNPs) in immunoregulatory genes in the morbidity of preterm newborns.

BACKGROUND: Prematurity is the main cause of perinatal and neonatal morbidity and mortality worldwide. Single nucleotide polymorphisms (SNPs) have been associated with the pathogenesis of morbidities in preterm neonates. We aimed to investigate the association between SNPs in regulatory genes of innate immune response IL1B, IL6, IL6R, IL10, TNFA, TNFRII, TLR2 and TLR4 and neonatal/infant morbidities in preterm newborns. METHODS: Oral swabs were collected from 272 newborns (91 preterm and 181 at term) seen at Botucatu Medical School, Unesp, between 2013 and 2014 and SNPs were identified using Taqman® Genotyping Assays. Medical records were examined to obtain data regarding neonatal/infant morbidity. Stepwise binomial logistic regression models were used to explain the morbidities. RESULTS: Minor neonatal morbidity was influenced by the clinical parameters of maternal age and newborn weight at birth and by the presence of the allele IL6R2 C (rs2228145) while major neonatal morbidity was only influenced by gestational age. Minor infant morbidity was associated with the allele TLR2 T (rs4696480) and major infant morbidity was associated with gestational age and presence of IL6R2 C. CONCLUSION: The presence of SNPs that exacerbate the inflammatory response increases the susceptibility to neonatal and infant morbidity.