Background: Approximately 3.8 billion people in low- and middle-income countries use unclean fuels as a source of primary cooking fuel as well as for heating. For pregnant women, the toxic chemicals produced by combustion of unclean fuels not only affect women’s health directly, but particulate matter and carbon monoxide are absorbed in maternal blood and cross the placental barrier potentially affecting the fetus. Methods: This dissertation presents three manuscripts. The first is a systematic review examining birth outcomes related to household air pollution (HAP) from type of cooking fuel in low-and middle-income countries. PRISMA 2009 guidelines were used for this systematic review. The inclusion criteria were quantitative, peer reviewed journal articles published within a date range of May 1, 2013-June 12, 2021. The quality of available evidence was evaluated using the Office of Health Assessment and Translation (OHAT) risk of bias rating tool. The reviewed studies presented evidence for an increased risk of low birth weight (LBW), preterm birth (PTB), small for gestational age (SGA), stillbirth, neonatal mortality and reduction in birthweight with unclean fuel use compared to cleaner fuels. The second study’s objective was to evaluate the effects of a liquefied petroleum gas (LPG) stove and fuel intervention during pregnancy on congenital anomalies, stillbirth and neonatal mortality using data from the Household Air Pollution Intervention Network (HAPIN) Trial. The HAPIN trial is a randomized controlled trial of LPG stoves and fuel distribution in nearly 3200 households conducted across India, Guatemala, Peru and Rwanda. Participants in the HAPIN Trial were monitored for adverse and serious adverse events. All analyses were performed according to intention-to-treat (ITT) analysis, and binary outcomes of congenital anomalies, stillbirth and neonatal mortality were compared between the two arms using log binomial models. The third study’s objective was to evaluate the effects of a LPG stove and fuel intervention during pregnancy on maternal outcomes of spontaneous abortion, postpartum hemorrhage, hypertensive disorders of pregnancy, and maternal mortality using data from the Household Air Pollution Intervention Network (HAPIN) Trial. All analyses were performed according to intention-to-treat (ITT) analysis, and binary outcomes of spontaneous abortion, postpartum hemorrhage, preeclampsia/eclampsia, and maternal mortality were compared between the two arms using log binomial models. Results: Systematically reviewing the evidence and risk of bias ratings illuminated several gaps in the current literature related to exposure assessment, outcome measurement and adequacy of adjustment for confounding. Results for the second study showed that adverse fetal and neonatal outcomes (congenital anomalies, stillbirth, neonatal mortality) did not differ based on stove type across four country research sites. Pregnant women assigned to the LPG intervention arm had a slightly lower risk of congenital anomaly (RR 0.96, 95% CI: 0.55, 1.70) and neonatal mortality (RR 0.97, 95% CI: 0.53, 1.77) compared to women in the control arm. In regards to stillbirth, pregnant women assigned to the LPG intervention arm had a slightly higher risk of stillbirth (RR 1.01, 95% CI: 0.60, 1.70) compared to women in the control arm. However these results were not statistically significant even after adjusting for maternal education, household food insecurity and bank account. Results for the third study demonstrated adverse maternal outcomes (spontaneous abortion, hypertensive disorders of pregnancy, postpartum hemorrhage and maternal mortality) did not differ based on stove type across the four country research sites. In intention-to-treat analyses we found women assigned to the LPG intervention arm had a higher risk of spontaneous abortion (RR 2.69, 95% CI: 0.71, 10.12) and maternal mortality (RR 1.51, 95% CI: 0.25, 9.03) compared to women in the control arm. Pregnant women assigned to the LPG intervention arm had a lower risk of postpartum hemorrhage (RR 0.84, 95% CI: 0.26, 2.74) and hypertensive disorders of pregnancy (RR 0.84, 95% CI: 0.26, 2.74) compared to women in the control arm. However all results were not statistically significant even after adjusting for maternal education, household food insecurity and bank account. Conclusion: The systematic review presented evidence for an increased risk of LBW, PTB, SGA, stillbirth, neonatal mortality and reduction in birthweight with solid fuel and kerosene use compared to cleaner fuels like gas and LPG. The HAPIN trial was the first multi-country RCT collecting data on household air pollution and health outcomes on pregnant women across four countries. While the LPG stove intervention did not significantly reduce the relative risk of adverse birth outcomes, women assigned to the LPG intervention arm had a slightly lower risk of congenital anomaly, neonatal mortality, hypertensive disorders of pregnancy and postpartum hemorrhage compared to women in the control arm. Access to sustainable and affordable energy should remain a priority for the global community.

Cardiac autonomic nervous system (ANS) measurements, respiratory sinus arrhythmia (RSA) and preejection period (PEP), are valid and reliable indicators of children’s sensitivity to stressors in their environment; however, there are few studies of RSA and PEP measures in children younger than three years of age and no known studies of children at 18-months of age. This was a cohort study of racially- and ethnically-diverse, low-income children studied from birth through five years of age. At 18-months (n = 134) and 36-months (n = 102) of age, children completed a developmentally challenging protocol that simultaneously assessed their RSA and PEP under resting and challenge conditions. Reactivity was calculated as the difference between challenge and resting measures. Four ANS profiles were created by dichotomizing reactivity, mean challenge minus rest, as positive or negative reactivity. This study revealed novel information about the distribution, stability, and continuity of RSA and PEP rest, challenge, and reactivity measures. There was a significantly different distribution of children among the ANS profiles from 18- to 36-months of age; although, there was some stability for the reciprocal PNS activation/SNS not activated profile. The relations between selected sociodemographic characteristics (biological sex, race, ethnicity, and federal poverty level (FPL)) and ANS profiles showed that their prevalence differed at 18- and 36-months of age. Logistic regression models revealed significant relationships between FPL and the coactivation and coinhibition profiles at 18-months and a borderline significant relationship between being Hispanic and the reciprocal SNS activation/PNS withdrawal profile at 36-months.

RISK OF PRETERM DELIVERY AND LOW BIRTH WEIGHT

IN SINGLETON PREGNANCIES CONCEIVED BY WOMEN

WITH AND WITHOUT A HISTORY OF INFERTILITY

Loretta B. Camarano

ABSTRACT

Aims: The objective of this study was to determine predictors of low birth weight (LBW) and preterm delivery (PTD) in singleton pregnancies conceived by women with a history of infertility compared to singleton pregnancies conceived spontaneously by fertile woman.

Methods: Data were collected at eleven infertility clinics in Northern California. Using a retrospective cohort design, record review was conducted on women who carried singleton pregnancies to greater than or equal to 20 weeks gestation between 1994 and 1998. These women were stratified by method of conception: women who conceived using infertility treatment (n=542), women who conceived naturally following a history of infertility (n=441), and fertile women (n= 1008) identified through California Vital Statistics records. Logistic regression was used to determine whether an association exists between LBW or PTD and infertility or infertility treatment compared to fertile women, controlling for potential confounding variables.

Results: There was no significant difference in the frequency of PTD between the three groups of women; however there was a significant difference in the frequency of LBW between the three groups of women (p< .05). 10.8 % of women in the infertile treatment group, 8.6% of women in the infertile without treatment group and 6.4% of women in the fertile group delivered a LBW infant. Women with a history of infertility who had treatment were 1.55 (CI 1.03, 2.34) times more likely to have a LBW infant compared to the fertile group controlling for maternal age, nulliparity, gestational diabetes, and obesity. There was no significant increased odds of delivery of a LBW infant for the infertile without treatment group compared to the fertile group, controlling for maternal age, nulliparity, gestational diabetes, and obesity. Nulliparity was a significant independent predictor of LBW (OR 1.51, CI 1.07, 2.14) in all three groups when controlling for maternal age, gestational diabetes and obesity regardless of fertility conception status.

Conclusion: Women with a history of infertility who undergo infertility treatment and conceive a singleton pregnancy are not at increased risk of preterm delivery but may be at increased risk for having a LBW infant.

Background: Research designed to understand and improve the environmental health and safety of early care and education (ECE) programs is important given the potential impact of environmental exposures on young children’s health and development.

Objectives: The main aims of this dissertation are to (1) synthesize the current evidence of the association between early child care attendance and the risk of childhood asthma and wheezing, (2) assess the demographic characteristic that are associated with in the prevalence of pesticide use and IPM knowledge among different regions of California, and (3) describe the frequency of key national health and safety standards in family child care homes (FCCHs) using the Health and Safety Checklist for Early Care and Education Programs (HSC).

Methods: This dissertation consists of three independent studies: (1) a meta-analysis of 32 studies to measure the association between early care and education program attendance and childhood asthma or wheeze, (2) a cross- sectional analysis of the pest management practices and knowledge of integrated pest management (IPM) of 45 child care centers by their geographic region of California, and (3) a cross-sectional pilot study assessing national standards for health and safety using a standardized HSC in 21 FCCHs in California.

Results: The main findings from this dissertation include (1) Early child care attendance is not significantly associated with the risk of asthma or wheeze in children 6 years of age or older, (2) pest management practices in child care center facilities differs by geographic region, and (3) the HSC is a feasible tool to measure health and safety in FCCHs.

Conclusion: Although early attendance in ECE programs doesn’t increase the risk of asthma or wheezing older children, young children in ECE programs continue to be exposed to pesticide application in ECE facilities and poor hygiene practices that can increase their potential exposure to infectious diseases. The findings from these three studies have important implications for parents, ECE providers, pediatric nurses and medical providers. Interventions to address the health and safety quality of ECE programs are needed to improve the overall environmental health of children in ECE settings.

Background: Children with chronic respiratory failure often require long-term mechanical ventilation via tracheostomy (LTMV-T). Advances in medical care have increased the number of children discharged from hospitals on LTMV-T, with home as the preferred care setting due to improved quality of life and reduced risk of infections. However, hospital readmission remains common, and transitioning from hospital to home presents complex challenges for caregivers at home (i.e., biological family members, non-biological guardian/foster parents). These include limited access to home health nursing, inconsistent delivery of essential supplies, and steep learning curves in managing complex medical needs at home. Structural and social barriers can undermine the caregivers ability to provide safe care at home, potentially resulting in readmission or institutionalization.

While the role of individual-level social determinants of health (SDOH) such as insurance status has been explored, the impact of broader, neighborhood-level SDOH on outcomes like discharge disposition and readmission remains understudied in this population. Emerging evidence points to disparities in access to home health nursing and discharge options (i.e., home, home health, or skilled facility), particularly among historically underserved populations. Measures like the Child Opportunity Index (COI), which capture neighborhood-level SDOH, may offer deeper insight into these disparities. However, studies examining COI or other composite SDOH indices among children on LTMV-T are limited. To address these gaps, this dissertation research aimed to explore neighborhood-level disparities in discharge disposition and subsequent readmissions, with the goal of better understanding how structural inequities influence care and outcomes for children on LTMV-T.Methods: A systematic review of quantitative studies examined the modifiable and non-modifiable risk factors associated with readmission and mortality in infants, children, and adolescents less than 21 years of age on LTMV-T (Chapter 2). Five databases (PubMed, CINAHL, Web of Science, Embase, and Epistemonikos) were searched from inception to 2024 and articles were limited to peer-reviewed journals and the English language. Covidence software was used for data management, study screening by two independent reviewers, and data extraction. The Joanna Briggs Institute critical appraisal tools were used to assess risk of bias of individual studies.

A secondary analysis of a multicenter retrospective cohort study of children aged 0-18 years newly discharged with LTMV-T between 2014-2023 was conducted using the Pediatric Health Information System (PHIS) database (Chapter 3). The PHIS database is a national administrative database of de-identified medical and billing information from 50+ tertiary care children’s hospitals. The primary outcome was discharge disposition, defined as home (with or without home health) or skilled facility. The primary predictor was the COI, reported in quintiles (very low to very high opportunity) with higher opportunity indicating better neighborhood conditions. Multivariable mixed-effects logistic regression model with a random effect for hospital clustering was used to analyze the association between COI and discharge disposition.

The same multicenter retrospective cohort study of children aged 0-18 years newly discharged to home, home health, or long-term skilled facility with LTMV-T between 2014-2023 was analyzed using the Pediatric Health Information System (PHIS) database (Chapter 4). The primary outcome was time to first all-cause same-hospital readmission to an observation or inpatient unit. The predictor was the Child Opportunity Index (COI), reported in quintiles (very low to very high opportunity). Multivariable mixed-effects Cox proportional hazards model with a random effect for hospital clustering was used to analyze the association between COI and time to first all-cause same-hospital readmission.

Results: The systematic review identified 26 studies that examined cohorts of children on LTMV-T from 1980 to 2023. Most studies reported that at least 50% of readmissions occurred within the first two years post-discharge and respiratory-related issues accounted for 30% to 75% of readmissions. Mortality within the first-year post-discharge varied as low as 0% to as high as 16%. Few studies examined socioenvironmental risk factors or those specific to LTMV-T populations, conducting analyses primarily on tracheostomy-only and/or LTMV-T cohorts. Risk factors for readmission and mortality were primarily clinical characteristics that reflected acuity including age, discharge disposition, chronic conditions, respiratory treatments, medical devices, birth weight, income, and insurance. Risk of bias ranged from low to moderate due to unclear outcome measures and analyses that did not address potential confounders.

Of the 5042 eligible children in the secondary analysis, 1011 (20%) children on LTMV-T were discharged to a skilled facility and 51% (n=2554) lived in very low to low COI neighborhoods. Compared to children from very high opportunity neighborhoods, children from very low (aOR= 3.10, 95% CI: 2.29-4.19), low (aOR=2.21, 95% CI: 1.62–3.02), moderate (aOR=2.19, 95% CI: 1.60–2.99), and high COI (aOR=1.64, 95% CI: 1.20-2.26) had increased odds of being discharged to skilled facility than home. Other factors associated with discharge to skilled facility included younger age at discharge, shorter length of stay, and pediatric or neonatal intensive care unit discharge.

Of the 4,268 eligible children in the secondary analysis, 85% (n=3615) of the children on LTMV-T were readmitted, with 28% being readmitted within 30 days and 50% by 107 days. Over half of the cohort lived in very low to low opportunity neighborhoods. No significant association was found between COI and time to first all-cause same-hospital readmission (very low versus very high opportunity: adjusted Hazard Ratio (aHR)=0.95, 95% CI: 0.85-1.07). Other factors associated with readmission included older age at discharge (12-18 years vs <6 months; aHR=0.77, 95% CI: 0.66-0.89), NICU discharge (vs other wards; aHR=0.82, 95% CI: 0.73-0.92), and length of stay (per 30 days; aHR=1.01, 95% CI: 1.01-1.02).

Conclusion: Children on LTMV-T are high risk for neighborhood-level SDOH disparities, increased likelihood of discharge to skilled facility, and early readmission. Health care institutions, clinicians, and community partners should collaborate to implement interventions and policies to improve neighborhood opportunities, reduce the number of early readmissions, and improve the ability for families and children on LTMV-T to be discharged to their home. This dissertation research has provided evidence of structural disparities at the neighborhood level for discharge disposition, however further research is needed to understand the interactions of multiple pathways and identify other mechanisms of inequities not captured in this dissertation.

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