Sequoia Foundation

There are known health concerns linked to prenatal tobacco and cannabis exposures. This study aims to objectively determine the level of exposure to tobacco and cannabis in pregnant individuals from six race/ethnicity groups (Black, Hispanic, Asian Indian, Native American, Vietnamese, and White) in the first three years following legalization of recreational marijuana use in 2018 in California. We used a cross-sectional sample of prenatal screening program participants (2018–2020) from southern and central California (N = 925). Exposures were estimated by a lab analysis of cotinine (tobacco) and 11-hydroxy-Δ9-tetrahydrocannabinol (OH-THC, cannabis) in banked serum. Disparities in tobacco exposure were evident, with Black subjects experiencing the highest smoking rate (16%) followed by Native American (10%) and White (8%) subjects, and ≤2% among Hispanic, Asian Indian, and Vietnamese subjects. Environmental tobacco exposure generally showed a similar pattern of exposure to tobacco smoking across race/ethnicity groups. Cannabis detection ranged from 5% among Hispanic subjects to 12% and 13% among White and Black subjects, respectively, and was higher among tobacco users and those exposed to environmental tobacco smoke than those with no cotinine detected. Tobacco and cannabis exposure were generally greatest in younger subjects and those with indices of a lower economic status; however, among Black subjects, cannabis exposure was greatest in older subjects and those with a higher socioeconomic status. Race/ethnicity, age, and socioeconomic factors can inform targeting of high-exposure groups for intervention.

Background and Aim: Prenatal exposure to endocrine-disrupting chemicals (EDCs) has been linked to child neurodevelopmental disorders. Maternal immune activation during pregnancy is associated with adverse child developmental outcomes. Whether EDCs influence maternal immune physiology is unclear. Methods: We analyzed data from general population controls (n=439) of the Early Markers for Autism (EMA) Study, a case-control study of children born during 2000-2003 in Southern California. Eleven polychlorinated biphenyls (PCBs), 6 brominated flame retardants (BFRs), 2 organochlorine pesticides (OCPs), 6 polyfluoroalkyl substances (PFAS), and 22 cytokines/chemokines were measured in maternal serum samples collected 15-20 weeks into pregnancy. We assessed individual relationships between log-transformed EDC levels and immune markers with spearman correlations and adjusted linear regression models. We further explored overall associations of EDC mixtures with specific immune markers using Bayesian kernel machine regression (BKMR). Results: After adjustment for false-discovery rate, 28 correlations between EDCs and maternal immune markers were statistically significant (spearman rho ranging from -0.25 to 0.24). These top correlations comprised 14 chemicals (9 PCBs, 3 PFAS, 1 BFR, and 1 OCP), and 8 immune markers. In adjusted linear models, all PCBs were inversely associated with levels of soluble interleukin-2 receptor alpha (sIL-2ra), with PCB99 showing the strongest relationship (adj-β[95%CI]: -0.48[-0.69, -0.27]). In BKMR, increasing all congeners in the PCB mixture from their 50th to their 95th percentiles was associated with decreased sIL-2ra (adj-β[95%CrI]: -0.43[-0.84, -0.02] and PCB99 had the highest relative importance in this mixture. Among other EDCs, p,p´-DDE, an OCP, was inversely associated with multiple markers (IL-12p40, IL-13, and IL-1ra). In contrast, others, such as Et-FOSAA, a PFAS, were positively associated with multiple immune markers, including IL-12p70, GM-CSF, IL-1ra, and IL-10. Conclusions: These findings suggest that specific EDCs may affect diverse immune and inflammatory pathways during pregnancy. These relationships may have implications for child development. Keywords: EDCs; prenatal; immune

Previous studies on in utero exposure to maternal environmental tobacco smoke (ETS) or maternal active smoking and Autism Spectrum Disorder (ASD) have not been entirely consistent, and no studies have examined in utero cotinine concentrations as an exposure classification method. We measured cotinine in stored second trimester maternal serum for 498 ASD cases and 499 controls born in California in 2011-2012. We also obtained self-reported maternal cigarette smoking during and immediately prior to pregnancy, as well as covariate data, from birth records. Using unconditional logistic regression, we found no association between log10 cotinine concentrations and odds for developing ASD among children of non-smokers (aOR: 0.93 [95% CI: 0.69, 1.25] per ng/ml), which represents exposure to ETS, though there may be a possible interaction with race. We found no association between cotinine-defined smoking (≥3.08 ng/ml vs. <3.08 ng/ml) (adjusted odds ratio [aOR]: 0.73 (95% confidence interval [95% CI]: 0.35, 1.54)) or self-reported smoking (aOR: 1.64 [95% CI: 0.65, 4.16]) and ASD. In one of the few studies of ETS and the first with measured cotinine, our results indicate no overall relationship between in utero exposure to tobacco smoke from maternal ETS exposure or active smoking, and development of ASD. LAY SUMMARY: This study found that women who smoke or are exposed to tobacco smoke during pregnancy are not more likely to have children with Autism Spectrum Disorder (ASD). This is the first ASD study to measure a chemical in the mother's blood during pregnancy to identify exposure to tobacco smoke.

Vitamin D is essential for several physiological functions and biological processes. Increasing levels of maternal vitamin D are required throughout pregnancy as a unique source of vitamin D for the fetus, and consequently maternal vitamin D deficiency may result in several adverse outcomes in newborns. However, the genetic regulation of vitamin D in pregnancy and at birth is not yet well understood. We performed genome-wide association studies of maternal midgestational serum-derived and neonatal blood-spot-derived total 25-hydroxyvitamin D from a case-control study of autism spectrum disorder (ASD). We identified one fetal locus (rs4588) significantly associated with neonatal vitamin D levels in the GC gene, encoding the binding protein for the transport and function of vitamin D. We also found suggestive cross-associated loci for neonatal and maternal vitamin D near immune genes, such as CXCL6-IL8 and ACKR1 We found no interactions with ASD. However, when including a set of cases with intellectual disability but not ASD (N = 179), we observed a suggestive interaction between decreased levels of neonatal vitamin D and a specific maternal genotype near the PKN2 gene. Our results suggest that genetic variation influences total vitamin D levels during pregnancy and at birth via proteins in the vitamin D pathway, but also potentially via distinct mechanisms involving loci with known roles in immune function that might be involved in vitamin D pathophysiology in pregnancy.

Background/Aim: Recent research supports the importance of environmental factors in the etiology of ASD. Vitamin D deficiency has increased concurrently with ASD prevalence and evidence for vitamin D’s role in brain and immune function has led to interest in associations with ASD. Generally, prior studies have examined surrogates of vitamin D or levels after ASD diagnosis, not during critical fetal developmental periods. Our goal is to address these gaps. Methods: We conducted a case-control study among children born 2000-2003 in Southern California who had banked biospecimens available from routine screening. Autism cases (N=563) were identified through the CA Department of Developmental Services and controls (N=436) were selected from general population births. 25-Hydroxyvitamin D (25OHD) was measured in maternal serum collected at 14-20 weeks gestation and newborn blood spots. Vitamin D levels were categorized as deficient (&lt;50nmol/L), insufficient (50-74nmol/L) and sufficient (≥ 75nmol/L, referent category). Crude and adjusted odds ratios (AOR) and 95% confidence intervals (CI) were calculated. Results: 25OHD was deficient in 9.5% and insufficient in 26% of mothers. 25OHD levels were lower during winter and among mothers of non-White race/ethnicity, but were similar between cases and controls. The AOR (95%CI) for maternal deficiency was 0.79 (0.49-1.3) and for insufficiency was 0.94 (0.68-1.3). Stratifying by parity or maternal race/ethnicity did not yield meaningful differences. By sex, female children of 25OHD-deficient mothers had lower ASD risk, based on small numbers. Conclusions: In this first large study to examine prenatal vitamin D levels in relation to clinical ASD, we saw no association, in contrast to the hypothesis. Our findings with newborn 25OHD levels and ASD were similarly null. Prior studies reporting lower Vitamin D levels in children already diagnosed with ASD may reflect current lifestyle and diet. Future analyses will examine vitamin D’s role in protecting against environmental exposure effects on ASD risk.

The risk of abnormalities and morbidity among live births increases with advanced maternal age. Explanations for this elevated morbidity invoke several maternal mechanisms. The relaxed filter stringency (RFS) hypothesis asserts that mothers, nearing the end of their reproductive lifespan, reduce the stringency of a screen of offspring quality in utero based on life-history traits of parity and interbirth interval (IBI). A separate line of research implicates human chorionic gonadotropin (hCG) during pregnancy as a signal of offspring quality. We test the RFS hypothesis directly by examining whether the difference in gestational hCG across consecutive live births varies positively with the mother's number of previous live births but inversely with her most recent IBI. We applied multivariable regression methods to a unique dataset of gestational hCG for over 500 000 live births from 2002 to 2007. The difference in gestational hCG across mothers' consecutive live births varies positively with both mothers' parity and IBI. These associations remain similar among older mothers (35+ years). Findings support the RFS hypothesis for the parity expectation but not for the IBI expectation. Further evidence for the RFS hypothesis among contemporary human gestations would have to invoke screening mechanisms other than hCG.

Little is known about modifiable lifestyle factors beyond quitting smoking that could prevent preterm delivery (PTD, <37 weeks gestation). We examined the individual and joint associations of pre-pregnancy BMI, second trimester exercise and sleep on PTD. We conducted a nested, population-based case-control study interviewing postpartum 344 cases delivering at <37 weeks, as identified by clinical estimate of gestational age from prenatal screening records, and 698 term controls, excluding term low birthweight. Eligible women participated in California's statewide Prenatal Screening Program, worked during pregnancy, and delivered a singleton birth in Southern California in 2002-2003. Modeled separately, moderate (odds ratio [OR] = 0.90; 95% confidence interval [CI] = 0.84-0.96--per hour/week) and vigorous (OR = 0.67; 95% CI = 0.46-0.98 for yes vs. no) exercise during the second trimester were associated with a reduced odds of PTD, and sleep duration was not (OR = 1.09, 95% CI = 0.80-1.48 for <7 h; OR = 0.88, 95% CI = 0.57-1.48 for >8 h vs. 7-8 h). When sleep and exercise variables were modeled together along with pre-pregnancy BMI, only moderate exercise (OR = 0.91; 95% CI 0.85-0.98) continued to be associated with reduced odds of PTD. The benefits of moderate exercise appeared strongest for women with BMI greater than 24 kg/m(2) (OR = 0.85; 95% CI = 0.79-0.93) and weakened with decreasing BMI. No other interactions were found. Moderate exercise is associated with reduced PTD, particularly for women with BMI above the normal range. The results are of public health relevance given that these risk factors are potentially modifiable both pre-conceptionally and during pregnancy and rates of PTD are still high in the United States.

Birth certificate last menstrual period (LMP) date is widely used to estimate gestational age in the US. While data quality concerns have been raised, no large population-based study has isolated data quality issues by comparing birth record LMP (Birth LMP) with reliable LMP dates from another source. We assessed LMP data quality in 2002 California singleton livebirth records (n = 515 381) and in a subset of records with linked prenatally collected LMP from California's statewide Prenatal Expanded Alpha-fetoprotein Screening Program (XAFP) (n = 105 936). Missing or incomplete LMP data affected 13% of birth records; 17% of those had complete LMP within XAFP records. Data quality indicators supported XAFP LMP as more accurate than Birth LMP, with a lower prevalence of digit preference, post-term delivery, out-of-range gestational age estimates and implausible birthweight-for-gestational age. The bimodal birthweight distribution evident at 20-31 weeks' gestation based on Birth LMP was nearly absent with XAFP LMP-based gestational age. Approximately 32% of the second birthweight mode was explained by apparent clerical errors in Birth LMP month. Digit preference errors, particularly day 1, were associated with gestational age overestimation. Preterm delivery rates were higher according to Birth (7.6%) vs. XAFP LMP (7.2%). One-fifth of observed preterm and over half of observed post-term births using Birth LMP were not true cases; 15% of true preterm cases were missed. African American or Hispanic, less educated, and publicly or uninsured women were most likely to be misclassified and have large LMP date discrepancies attributable to clerical or digit preference error. The implementation of a revised birth certificate is an opportunity for targeted training and data entry checks that could substantially improve LMP accuracy on birth records.