US Birth Research Articles

Informing the ‘Broad Masses’: Early‐Twentieth‐Century Birth Control Debates and Activism in the Polish‐American Community

AbstractDuring 1925–26 and 1928, debates about birth control took place in the readers' column of North Star (Gwiazda Polarna), a US Polish language weekly. These discussions provide a rare insight into how ideas spread by the US birth control movement were received by an immigrant and ethnic working‐class Catholic community. The readers’ letters showed the prevalence of socialist rationales for birth control, expectation from men to play an active role in family limitation, the lack of references to women's sexual pleasure and an ambivalence towards the teachings of the Catholic Church. In the wake of the discussion, one North Star editor established a birth control association to inform the ‘broad masses’. This role was also played by the North Star letters, which spread family planning information and dispelled the misconceptions regarding birth control possessed by many Polish‐Americans at that time.

Approaches to developing de novo cancer population models to examine questions about cancer and race in bladder, gastric, and endometrial cancer and multiple myeloma: the Cancer Intervention and Surveillance Modeling Network incubator program.

We are developing 10 de novo population-level mathematical models in 4 malignancies (multiple myeloma and bladder, gastric, and uterine cancers). Each of these sites has documented disparities in outcome that are believed to be downstream effects of systemic racism. Ten models are being independently developed as part of the Cancer Intervention and Surveillance Modeling Network incubator program. These models simulate trends in cancer incidence, early diagnosis, treatment, and mortality for the general population and are stratified by racial subgroup. Model inputs are based on large population datasets, clinical trials, and observational studies. Some core parameters are shared, and other parameters are model specific. All models are microsimulation models that use self-reported race to stratify model inputs. They can simulate the distribution of relevant risk factors (eg, smoking, obesity) and insurance status (for multiple myeloma and uterine cancer) in US birth cohorts and population. The models aim to refine approaches in prevention, detection, and management of 4 cancers given uncertainties and constraints. They will help explore whether the observed racial disparities are explainable by inequities, assess the effects of existing and potential cancer prevention and control policies on health equity and disparities, and identify policies that balance efficiency and fairness in decreasing cancer mortality.

Maternal hepatitis C virus infection and three adverse maternal outcomes in the United States.

Hepatitis Virus C (HCV) infection rates have trended upwards among pregnant people in the USA since 2009. Existing evidence about HCV infections and maternal outcomes is limited; therefore, we used birth certificate data to investigate the association between HCV infection and maternal health outcomes. We used the 2017 US birth certificate dataset (a cross-section of 1.4 million birth records) to assess the association between prevalent HCV infection and gestational diabetes, gestational hypertension, and eclampsia. Potential confounding variables included prenatal care, age, education, smoking, presence of sexually transmitted infections (STIs), body mass index (BMI), and weight gain during pregnancy. We restricted our analysis to only women with a first singleton pregnancy. Odds ratios were estimated by logistic regression models and separate models were tested for white and Black women. Only 0.31% of the women in our sample were infected with HCV (n = 4412). In an unadjusted model, we observed a modest significant protective association between HCV infection and gestational diabetes (Odds ratio [OR]: 0.83; 95% CI: 0.76-0.96); but this was attenuated with adjustment for confounding variables (Adjusted odds ratio [AOR]: 0.88; 95% CI: 0.76, 1.02). There was no association between HCV and gestational hypertension (AOR: 1.03; 95% CI: 0.91, 1.16) or eclampsia (AOR: 1.15; 95% CI: 0.69, 1.93). Results from the race stratified models were similar to the non-stratified summary models. We observed no statistically significant associations between maternal HCV infection with maternal health outcomes. Although, our analysis did indicate that HCV may lower the risk of gestational diabetes, this may be attributable to confounding. Studies utilizing more accurately measured HCV infection including those collecting type and timing of testing, and timing of infection are warranted to ensure HCV does not adversely impact maternal and/or fetal health. Particularly in the absence of recommended therapy for HCV during pregnancy.

Disability and morbidity among US birth cohorts, 1998–2018: A multidimensional test of dynamic equilibrium theory

A substantial body of prior research has explored patterns of disability-free and morbidity-free life expectancy among older populations. However, these distinct facets of later-life health are almost always studied in isolation, even though they are very likely to be related. Using data from the US Health and Retirement Study and a multistate life table approach, this paper explores the interactions between disability, morbidity, and mortality by sex and education among four successive US birth cohorts, born from 1914 to 1923 to 1944–1953 and compared in the periods 1998–2008 and 2008–2018. We find little compression of disability but a marked expansion of morbidity across cohorts. However, disability-free life expectancy (DFLE) among those living with chronic morbidities has increased, even though at the population-level DFLE is largely unchanged. Broadly, these patterns suggest that successive cohorts of older populations in the US are experiencing a dynamic equilibrium, where the link between chronic morbidities and disability has weakened over successive cohorts. Investigating patterns by educational attainment, we find marked disparities where the least educated individuals not only live significantly fewer years free of disabilities or chronic morbidities but also have experienced an expansion in morbidity and disability. Our findings suggest that the future trajectory of disability-free life expectancy in the US is increasingly contingent on efforts to improve disease management and control the severe consequences of chronic morbidities.

Prenatal Exposure to Nonpersistent Environmental Chemicals and Postpartum Depression

Postpartum depression (PPD) affects up to 20% of childbearing individuals, and a significant limitation in reducing its morbidity is the difficulty in modifying established risk factors. Exposure to synthetic environmental chemicals found in plastics and personal care products, such as phenols, phthalates, and parabens, are potentially modifiable and plausibly linked to PPD and have yet to be explored. To evaluate associations of prenatal exposure to phenols, phthalates, parabens, and triclocarban with PPD symptoms. This was a prospective cohort study from 5 US sites, conducted from 2006 to 2020, and included pooled data from 5 US birth cohorts from the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) consortium. Participants were pregnant individuals with data on urinary chemical concentrations (phenols, phthalate metabolites, parabens, or triclocarban) from at least 1 time point in pregnancy and self-reported postnatal depression screening assessment collected between 2 weeks and 12 months after delivery. Data were analyzed from February to May 2022. Phenols (bisphenols and triclosan), phthalate metabolites, parabens, and triclocarban measured in prenatal urine samples. Depression symptom scores were assessed using the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiologic Studies Depression Scale (CES-D), harmonized to the Patient-Reported Measurement Information System (PROMIS) Depression scale. Measures of dichotomous PPD were created using both sensitive (EPDS scores ≥10 and CES-D scores ≥16) and specific (EPDS scores ≥13 and CES-D scores ≥20) definitions. Among the 2174 pregnant individuals eligible for analysis, nearly all (>99%) had detectable levels of several phthalate metabolites and parabens. PPD was assessed a mean (SD) of 3 (2.5) months after delivery, with 349 individuals (16.1%) and 170 individuals (7.8%) screening positive for PPD using the sensitive and specific definitions, respectively. Linear regression results of continuous PROMIS depression T scores showed no statistically significant associations with any chemical exposures. Models examining LMW and HMW phthalates and di (2-ethylhexyl) phthalate had estimates in the positive direction whereas all others were negative. A 1-unit increase in log-transformed LMW phthalates was associated with a 0.26-unit increase in the PROMIS depression T score (95% CI, -0.01 to 0.53; P = .06). This corresponded to an odds ratio (OR) of 1.08 (95% CI, 0.98-1.19) when modeling PPD as a dichotomous outcome and using the sensitive PPD definition. HMW phthalates were associated with increased odds of PPD (OR, 1.11; 95% CI, 1.00-1.23 and OR, 1.10; 95% CI, 0.96-1.27) for the sensitive and specific PPD definitions, respectively. Sensitivity analyses produced stronger results. Phthalates, ubiquitous chemicals in the environment, may be associated with PPD and could serve as important modifiable targets for preventive interventions. Future studies are needed to confirm these observations.

National Trends in Preterm Infant Mortality in the United States by Race and Socioeconomic Status, 1995-2020

Inequalities in preterm infant mortality exist between population subgroups within the United States. To characterize trends in preterm infant mortality by maternal race and socioeconomic status to assess how inequalities in preterm mortality rates have changed over time. This was a retrospective longitudinal descriptive study using the US National Center for Health Statistics birth infant/death data set for 12 256 303 preterm infant births over 26 years, between 1995 and 2020. Data were analyzed from December 2022 to March 2023. Maternal characteristics including race, smoking status, educational attainment, antenatal care, and insurance status were used as reported on an infant's US birth certificate. Preterm infant mortality rate was calculated for each year from 1995 to 2020 for all subgroups, with a trend regression coefficient calculated to describe the rate of change in preterm mortality. The average US preterm infant mortality rate (IMR) decreased from 33.71 (95% CI, 33.71 to 34.04) per 1000 preterm births per year between 1995-1997, to 23.32 (95% CI, 23.05 to 23.58) between 2018-2020. Black non-Hispanic infants were more likely to die following preterm births than White non-Hispanic infants (IMR, 31.09; 95% CI, 30.44 to 31.74, vs 21.81; 95% CI, 21.43 to 22.18, in 2018-2020); however, once born, extremely prematurely Black and Hispanic infants had a narrow survival advantage (IMR rate ratio, 0.87; 95% CI, 0.84 to 0.91, in 2018-2020). The rate of decrease in preterm IMR was higher in Black infants (-0.015) than in White (-0.013) and Hispanic infants (-0.010); however, the relative risk of preterm IMR among Black infants compared with White infants remained the same between 1995-1997 vs 2018-2020 (relative risk, 1.40; 95% CI, 1.38 to 1.44, vs 1.43; 95% CI, 1.39 to 1.46). The rate of decrease in preterm IMR was higher in nonsmokers compared with smokers (-0.015 vs -0.010, respectively), in those with high levels of education compared with those with intermediate or low (-0.016 vs - 0.010 or -0.011, respectively), and in those who had received adequate antenatal care compared with those who did not (-0.014 vs -0.012 for intermediate and -0.013 for inadequate antenatal care). Over time, the relative risk of preterm mortality widened within each of these subgroups. This study found that between 1995 and 2020, US preterm infant mortality improved among all categories of prematurity. Inequalities in preterm infant mortality based on maternal race and ethnicity have remained constant while socioeconomic disparities have widened over time.

Association between acetaminophen metabolites and CYP2E1 DNA methylation level in neonate cord blood in the Boston Birth Cohort

BackgroundAcetaminophen is a commonly used medication by pregnant women and is known to cross the placenta. However, little is known about the biological mechanisms that regulate acetaminophen in the developing offspring. Cytochrome 2E1 (CYP2E1) is the primary enzyme responsible for the conversion of acetaminophen to its toxic metabolite. Ex vivo studies have shown that the CYP2E1 gene expression in human fetal liver and placenta is largely controlled by DNA methylation (DNAm) at CpG sites located in the gene body of CYP2E1 at the 5’ end. To date, no population studies have examined the association between acetaminophen metabolite and fetal DNAm of CYP2E1 at birth.MethodsWe utilized data from the Boston Birth Cohort (BBC) which represents an urban, low-income, racially and ethnically diverse population in Boston, Massachusetts. Acetaminophen metabolites were measured in the cord plasma of newborns enrolled in BBC between 2003 and 2013 using liquid chromatography-tandem mass spectrometry. DNAm at 28 CpG sites of CYP2E1 was measured by Illumina Infinium MethylationEPIC BeadChip. We used linear regression to identify differentially methylated CpG sites and the “DiffVar” method to identify differences in methylation variation associated with the detection of acetaminophen, adjusting for cell heterogeneity and batch effects. The false discovery rate (FDR) was calculated to account for multiple comparisons.ResultsAmong the 570 newborns included in this study, 96 (17%) had detectable acetaminophen in cord plasma. We identified 7 differentially methylated CpGs (FDR < 0.05) associated with the detection of acetaminophen and additional 4 CpGs showing a difference in the variation of methylation (FDR < 0.05). These CpGs were all located in the gene body of CYP2E1 at the 5’ end and had a 3–6% lower average methylation level among participants with detectable acetaminophen compared to participants without. The CpG sites we identified overlap with previously identified DNase hypersensitivity and open chromatin regions in the ENCODE project, suggesting potential regulatory functions.ConclusionsIn a US birth cohort, we found detection of cord biomarkers of acetaminophen was associated with DNAm level of CYP2E1 in cord blood. Our findings suggest that DNA methylation of CYP2E1 may be an important regulator of acetaminophen levels in newborns.

The COVID-19 baby bump in the United States.

We use natality microdata covering the universe of US. births for 2015 to 2021 and California births from 2015 through February 2023 to examine childbearing responses to the COVID-19 pandemic. We find that 60% of the 2020 decline in US fertility rates was driven by sharp reductions in births to foreign-born mothers although births to this group comprised only 22% of all US births in 2019. This decline started in January 2020. In contrast, the COVID-19 recession resulted in an overall "baby bump" among US-born mothers, which marked the first reversal in declining fertility rates since the Great Recession. Births to US-born mothers fell by 31,000 in 2020 relative to a prepandemic trend but increased by 71,000 in 2021. The data for California suggest that US births remained elevated through February 2023. The baby bump was most pronounced for first births and women under age 25, suggesting that the pandemic led some women to start families earlier. Above age 25, the baby bump was most pronounced for women aged 30 to 34 and women with a college education. The 2021 to 2022 baby bump is especially remarkable given the large declines in fertility rates that would have been projected by standard statistical models.

Association of the 2021 Child Tax Credit Advance Payments With Low Birth Weight in the US

Infants and pregnant people in the US fare worse on almost all health measures compared with those in peer nations. Families in the US are more likely to live in poverty and have a less generous social safety net, which has generated debate over the contribution of economic conditions to this disparity. To assess the association between temporary increases in income during pregnancy through the 2021 expanded Child Tax Credit (CTC) and birth outcomes. This cross-sectional study applied a comparison-population, interrupted time series design to data from US birth certificates (January 1, 2014, through December 31, 2021) to test whether the log odds of low birth weight (LBW) among monthly cohorts of births exposed to the CTC would coincide with a decreased incidence of LBW. All singleton live births to US residents aged 15 to 49 years with available data were included. Monthly birth cohorts exposed to the CTC were defined as those born to parous people during the CTC advance payment period from July through December 2021. The main outcome was the natural logarithm of the odds of LBW (<2500 g) among monthly birth cohorts. Among included births (n = 28 866 466), 61.2% were to parous people, the majority were to people aged 20 to 39 years (91.7%), and 6.5% were born LBW. The odds of LBW increased above expected values in 5 of the 6 months of the CTC payments (range of increases, 3.3%-5.4% across the 5 months). The outlier-adjusted odds of LBW increased, on average, by 4.2% (95% CI, 2.7%-5.7%) among the monthly birth cohorts exposed to the CTC. This study found that the odds of LBW among birth cohorts exposed to the CTC increased above expected values in 5 of the 6 months of the CTC advance payments. Additional research is needed to evaluate rival explanations for this increase in LBW among births exposed to the CTC payments.

Small-for-Gestational-Age and Vocabulary and Achievement Test Scores at Age 9 Among Children Born at Term in a Contemporary U.S. Sample.

Children that are small-for-gestational-age (SGA) at birth are at an increased risk for cognitive impairment, even if born at term (37-41weeks). This study examined associations between sex-specific SGA and vocabulary and achievement tests in 9 year oldchildren born at term using a contemporary population-based US sample. A secondary data analysis was conducted on a sample of 2144 children born at term in 1998-2000 who participated in a US birth cohort study that oversampled non-marital births, which in the U.S.are associated with socioeconomic disadvantage and racial minority status. Vocabulary and achievement tests were administered to participants at age 9. Unadjusted and adjusted Ordinary Least Squares and logistic regression models of associations between SGA and test scores were estimated. Sex-specific SGA was associated with 2-5 point lower test scores and 1-2 times the odds of scores less than 85 (> 1 SD below the national mean) across most outcomes. In adjusted models, measures ofSGA were associated with low scores on the Woodcock-Johnson Applied Problems test (OR 2.257; 95% CI 1.434, 3.551) and the Woodcock-Johnson Passage Comprehension test (OR 1.554; 95% CI 1.132, 2.134). The findings validate previous studies of SGA at term and cognitive outcomes and provide further evidence using a contemporary high-risk population-based US sample. The findings suggest that SGA children born at term should be recruited for early interventions to promote improved cognitive functioning in school.

Survival From Birth Until Young Adulthood Among Individuals With Congenital Heart Defects: CH STRONG.

Limited population-based information is available on long-term survival of US individuals with congenital heart defects (CHDs). Therefore, we assessed patterns in survival from birth until young adulthood (ie, 35 years of age) and associated factors among a population-based sample of US individuals with CHDs. Individuals born between 1980 and 1997 with CHDs identified in 3 US birth defect surveillance systems were linked to death records through 2015 to identify those deceased and the year of their death. Kaplan-Meier survival curves, adjusted risk ratios (aRRs) for infant mortality (ie, death during the first year of life), and Cox proportional hazard ratios for survival after the first year of life (aHRs) were used to estimate the probability of survival and associated factors. Standardized mortality ratios compared infant mortality, >1-year mortality, >10-year mortality, and >20-year mortality among individuals with CHDs with general population estimates. Among 11 695 individuals with CHDs, the probability of survival to 35 years of age was 81.4% overall, 86.5% among those without co-occurring noncardiac anomalies, and 92.8% among those who survived the first year of life. Characteristics associated with both infant mortality and reduced survival after the first year of life, respectively, included severe CHDs (aRR=4.08; aHR=3.18), genetic syndromes (aRR=1.83; aHR=3.06) or other noncardiac anomalies (aRR=1.54; aHR=2.53), low birth weight (aRR=1.70; aHR=1.29), and Hispanic (aRR=1.27; aHR=1.42) or non-Hispanic Black (aRR=1.43; aHR=1.80) maternal race and ethnicity. Individuals with CHDs had higher infant mortality (standardized mortality ratio=10.17), >1-year mortality (standardized mortality ratio=3.29), and >10-year and >20-year mortality (both standardized mortality ratios ≈1.5) than the general population; however, after excluding those with noncardiac anomalies, >1-year mortality for those with nonsevere CHDs and >10-year and >20-year mortality for those with any CHD were similar to the general population. Eight in 10 individuals with CHDs born between1980 and 1997 survived to 35 years of age, with disparities by CHD severity, noncardiac anomalies, birth weight, and maternal race and ethnicity. Among individuals without noncardiac anomalies, those with nonsevere CHDs experienced similar mortality between 1 and 35 years of age as in the general population, and those with any CHD experienced similar mortality between 10 and 35 years of age as in the general population.

Geriatricians, general internists, and potentially inappropriate medications for a national sample of older adults.

Older adults are often prescribed medications that are potentially dangerous and geriatricians have specialized training in treating polypharmacy that may benefit these patients. To examine this, we compared potentially inappropriate medication (PIM) prescribing rates between geriatricians and similar general internists in the United States. Using national cross-sectional data from 2013 to 2019, we compared annual PIM prescribing rates between 2815 outpatient geriatricians certified by the American Board of Internal Medicine in 1994-2018 and general internists matched 1:1 on IM certification exam score and year, residency exam pass rate, gender, and US birth and/or US medical school. PIM prescribing was based on the Healthcare Effectiveness Data and Information Set (HEDIS) PIM physician annual prescribing measures which consider medications flagged as potentially inappropriate in the American Geriatric Society Beers Criteria® guideline. We also examined prescribing of appropriate alternative medications. Prescribing rates were calculated as the percentage a physician's patients with Medicare fee-for-service part D enrollment seen in the outpatient setting in a given year (mean: 150 patients per physician) with a PIM prescription they prescribed. Across 30,677 physician-year observations, geriatricians were 16.7% less likely (95% confidence interval (CI): -19.8 to -13.7, p < 0.001) to prescribe a PIM (7.2% versus 8.7% of patients respectively) and 2.7% more likely (95% CI: 0.8 to 4.5, p = 0.004) to prescribe an appropriate alternative medication (52.0% versus 50.7% of patients respectively). Lower PIM prescribing was observed for most medication sub-types including central nervous system, anticholinergic, pain, and endocrine medications. In sensitivity analyses, differences in prescribing were similar when comparing recently trained physicians with more experienced physicians. Findings suggest geriatricians in the United States prescribe PIMs at lower rates than general internists. This highlights the value geriatricians provide as well as opportunities to embed key principles of geriatric care into internal medicine training and health care delivery systems.

Medicaid expansion and risk of eclampsia

Eclampsia is an indicator of severe maternal morbidity and can be prevented through increased prenatal care access and early prenatal care utilization. The 2014 Medicaid expansion under the Patient Protection and Affordable Care Act allowed states to expand Medicaid coverage to nonelderly adults with incomes up to 138% of the federal poverty level. Its implementation has led to a significant increase in prenatal care access and utilization. This study aimed to assess the association of Medicaid expansion under the Affordable Care Act with eclampsia incidence. This natural experiment study was based on US birth certificate data from January 2010 to December 2018 in 16 states that expanded Medicaid in January 2014 and in 13 states that did not expand Medicaid during the study period. The outcome was eclampsia incidence, the intervention was the implementation of the Medicaid expansion, and the exposure was state expansion status. Using the interrupted time series method, we compared temporal trends in the incidence of eclampsia before and after the intervention in expansion vs non-expansion states with adjustments for patient and hospital county characteristics. Of the 21,570,021 birth certificates analyzed, 11,433,862 (53.0%) were in expansion states and 12,035,159 (55.8%) were in the postintervention period. The diagnosis of eclampsia was recorded in 42,677 birth certificates or 19.8 per 10,000 (95% confidence interval, 19.6-20.0). The incidence of eclampsia was higher for Black people (29.1 per 10,000) than for White (20.7 per 10,000), Hispanic (15.3 per 10,000), and birthing people of other race and ethnicity (15.4 per 10,000). In the expansion states, the incidence of eclampsia increased during the preintervention period and decreased during the postintervention period; in the nonexpansion states, a reverse pattern was observed. A statistically significant difference was observed between expansion and nonexpansion states in temporal trends between the pre- and postintervention periods, with an overall 1.6% decrease (95% confidence interval, 1.3-1.9) in the incidence of eclampsia in expansion states compared with nonexpansion states. The results were consistent in subgroup analyses according to maternal race and ethnicity, education level (less than high school or high school and higher), parity (nulliparous or parous), delivery mode (vaginal or cesarean delivery), and poverty in the residence county (high or low). Implementation of the Affordable Care Act Medicaid expansion was associated with a small statistically significant reduction in the incidence of eclampsia. Its clinical significance and cost-effectiveness remain to be determined.

Post Antenatal Late Preterm Steroids trial: interrupted time series analysis of respiratory outcomes in twin and pregestational diabetes

The Antenatal Late Preterm Steroids trial found that corticosteroid administration decreased respiratory complications by 20% among late preterm singleton deliveries. After the Antenatal Late Preterm Steroids trial, corticosteroid administration increased by 76% among twin pregnancies and 113% among singleton pregnancies complicated by pregestational diabetes mellitus compared with expected rates based on the pre-Antenatal Late Preterm Steroids trial trend. However, the effect of corticosteroids on twin pregnancies and pregnancies complicated by pregestational diabetes mellitus is not well studied, as the Antenatal Late Preterm Steroids trial excluded twin pregnancies and pregnancies complicated by pregestational diabetes mellitus. This study aimed to examine the change in the incidence rate of immediate assisted ventilation use and ventilation use for more than 6 hours among 2 populations after the dissemination of the Antenatal Late Preterm Steroids trial at the population level. This study was a retrospective analysis of publicly available US birth certificate data. The study period was from August 1, 2014, to April 30, 2018. The dissemination period of the Antenatal Late Preterm Steroids trial was from February 2016 to October 2016. Population-based interrupted time series analyses were performed for 2 target populations: (1) twin pregnancies not complicated by pregestational diabetes mellitus and (2) singleton pregnancies complicated by pregestational diabetes mellitus. For both target populations, analyses were limited to individuals who delivered nonanomalous live neonates between 34 0/7 and 36 6/7 weeks of gestation (vaginal or cesarean delivery). As a sensitivity analysis, a total of 23 placebo tests were conducted before (5 tests) and after (18 tests) the dissemination period. For the analysis of late preterm twin deliveries, 191,374 individuals without pregestational diabetes mellitus were identified. For the analysis of late preterm singleton pregnancy with pregestational diabetes mellitus, 21,395 individuals were identified. After the dissemination period, the incidence rate of immediate assisted ventilation use for late preterm twin deliveries was significantly lower than the expected value based on the pre-Antenatal Late Preterm Steroids trial trend (11.6% observed vs 13.0% expected; adjusted incidence rate ratio, 0.87; 95% confidence interval, 0.78-0.97). The incidence rate of ventilation use for more than 6 hours among late preterm twin deliveries did not change significantly after the dissemination of the Antenatal Late Preterm Steroids trial. A significant increase in the incidence rate of immediate assisted ventilation use and ventilation use for more than 6 hours was found among singleton pregnancies with pregestational diabetes mellitus. However, the results of placebo tests suggested that the increase in incidence was not necessarily due to the dissemination period of the Antenatal Late Preterm Steroids trial. The dissemination of the Antenatal Late Preterm Steroids trial was associated with decreased incidence of immediate assisted ventilation use, but no change in ventilation use for more than 6 hours, among late preterm twin deliveries in the United States. In contrast, the incidence of neonatal respiratory outcomes among singleton deliveries with pregestational diabetes mellitus did not decrease after the dissemination of the Antenatal Late Preterm Steroids trial.

Addressing the smoking-hypertension paradox in pregnancy: insight from a multiethnic US birth cohort.

Smoking during pregnancy has been associated with reduced risk of a spectrum of hypertensive (HTN) disorders, known as the "smoking-hypertension paradox." We sought to test potential epidemiologic explanations for the smoking-hypertension paradox. We analyzed 8510 pregnant people in the Boston Birth Cohort, including 4027 non-Hispanic Black and 2428 Hispanic pregnancies. Study participants self-reported tobacco, alcohol, cannabis, opioids, or cocaine use during pregnancy. We used logistic regression to assess effect modification by race/ethnicity, and confounding of concurrent substances on hypertensive disorders or prior pregnancy. We also investigated early gestational age as a collider or competing risk for pre-eclampsia, using cause-specific Cox models and Fine-Gray models, respectively. We replicated the paradox showing smoking to be protective against hypertensive disorders among Black participants who used other substances as well (aOR: 0.61, 95% CI: 0.41, 0.93), but observed null effects for Hispanic participants (aOR: 1.14, 95% CI: 0.55, 2.36). In our cause-specific Cox regression, the effects of tobacco use were reduced to null effects with pre-eclampsia (aOR: 0.81, 95% CI: 0.63, 1.04) after stratifying for preterm birth. For the Fine-Gray competing risk analysis, the paradoxical associations remained. The smoking paradox was either not observed or reversed after accounting for race/ethnicity, other substance use, and collider-stratification due to preterm birth. These findings offer new insights into this paradox and underscore the importance of considering multiple sources of bias in assessing the smoking-hypertension association in pregnancy.

Maternal Hepatitis C Virus Infection and Adverse Newborn Outcomes in the US.

We investigated the relationship between maternal hepatitis C virus (HCV) infection and infant health. Furthermore, we evaluated racial disparities with these associations. Using 2017 US birth certificate data, we investigated the association between maternal HCV infection and infant birthweight, preterm birth, and Apgar score. We used unadjusted and adjusted linear regression and logistic regression models. Models were adjusted for use of prenatal care, maternal age, maternal education, maternal smoking status, and the presence of other sexually transmitted infections. We stratified the models by race to describe the experiences of White and Black women separately. Maternal HCV infection was associated with reduced infant birthweight on average by 42.0g (95% CI: -58.81, -25.30) for women of all races, 64.6g (95% CI: -81.91, -47.26) for White women and 80.3g (95% CI: -162.48, 1.93) for Black women. Women with maternal HCV infection had increased odds of having a preterm birth of 1.06 (95% CI: 0.96, 1.17) for women of all races, 1.06 (95% CI: 0.96, 1.18) for White women and 1.35 (95% CI: 0.93, 1.97) for Black women. Overall, women with maternal HCV infection had increased odds 1.26 (95% CI: 1.03, 1.55) of having a low/intermediate Apgar score; White and Black women with HCV infection had similarly increased odds of an infant with low/intermediate Apgar score in a stratified analysis: 1.23 (95% CI: 0.98, 1.53) for White women and 1.24 (95% CI: 0.51, 3.02) for Black women. Maternal HCV infection was associated with lower infant birthweight and higher odds of having a low/intermediate Apgar score. Given the potential for residual confounding, these results should be interpreted with caution.

Burden of Respiratory Viruses in Children Less Than 2 Years Old in a Community-based Longitudinal US Birth Cohort.

Respiratory viral infections are a major cause of morbidity and hospitalization in young children. Nevertheless, the population burden of respiratory viral infections, especially asymptomatic cases, is not known due to the lack of prospective community-based cohort studies with intensive monitoring. To address this gap, we enacted the PREVAIL cohort, a Centers for Disease Control and Prevention-sponsored birth cohort in Cincinnati, Ohio, where children were followed from 0 to 2 years of age. Weekly text surveys were administered to record acute respiratory illnesses (ARIs), which were defined as the presence of cough or fever (≥38°C). Weekly midturbinate nasal swabs were collected and tested using the Luminex Respiratory Pathogen Panel, which detected 16 viral pathogens. Viral infection was defined as ≥1 positive tests from the same virus or viral subtype ≤30 days of a previous positive test. Maternal report and medical chart abstractions identified healthcare utilization. From 4/2017 to 7/2020, 245 mother-infant pairs were recruited and followed. From the 13 781 nasal swabs tested, a total of 2211 viral infections were detected, of which 821 (37%) were symptomatic. Children experienced 9.4 respiratory viral infections/child-year; half were rhinovirus/enterovirus. Viral ARI incidence was 3.3 episodes/child-year. Emergency department visits or hospitalization occurred with only 15% of respiratory syncytial virus infections, 10% of influenza infections, and only 4% of all viral infections. Regardless of pathogen, most infections were asymptomatic or mild. Respiratory viral infections are common in children 0-2 years. Most viral infections are asymptomatic or non-medically attended, underscoring the importance of community-based cohort studies.

Contrasting Association of Maternal Plasma Biomarkers of Smoking and 1-Carbon Micronutrients with Offspring DNA Methylation: Evidence of Aryl Hydrocarbon Receptor Repressor Gene–Smoking–Folate Interaction

BackgroundMaternal prenatal smoking is known to alter offspring DNA methylation (DNAm). However, there are no effective interventions to mitigate smoking-induced DNAm alteration. ObjectivesThis study investigated whether 1-carbon nutrients (folate, vitamins B6, and B12) can protect against prenatal smoking-induced offspring DNAm alterations in the aryl hydrocarbon receptor repressor (AHRR) (cg05575921), GFI1 (cg09935388), and CYP1A1 (cg05549655) genes. MethodsThis study included mother-newborn dyads from a racially diverse US birth cohort. The cord blood DNAm at the above 3 sites were derived from a previous study using the Illumina Infinium MethylationEPIC BeadChip. Maternal smoking was assessed by self-report and plasma biomarkers (hydroxycotinine and cotinine). Maternal plasma folate, and vitamins B6 and B12 concentrations were obtained shortly after delivery. Linear regressions, Bayesian kernel machine regression, and quantile g-computation were applied to test the study hypothesis by adjusting for covariables and multiple testing. ResultsThe study included 834 mother-newborn dyads (16.7% of newborns exposed to maternal smoking). DNAm at cg05575921 (AHRR) and at cg09935388 (GFI1) was inversely associated with maternal smoking biomarkers in a dose-response fashion (all P < 7.01 × 10−13). In contrast, cg05549655 (CYP1A1) was positively associated with maternal smoking biomarkers (P < 2.4 × 10−6). Folate concentrations only affected DNAm levels at cg05575921 (AHRR, P = 0.014). Regression analyses showed that compared with offspring with low hydroxycotinine exposure (<0.494) and adequate maternal folate concentrations (quartiles 2–4), an offspring with high hydroxycotinine exposure (≥0.494) and low folate concentrations (quartile 1) had a significant reduction in DNAm at cg05575921 (M-value, ß ± SE = −0.801 ± 0.117, P = 1.44 × 10−11), whereas adequate folate concentrations could cut smoking-induced hypomethylation by almost half. Exposure mixture models further supported the protective role of adequate folate concentrations against smoking-induced aryl hydrocarbon receptor repressor (AHRR) hypomethylation. ConclusionsThis study found that adequate maternal folate can attenuate maternal smoking-induced offspring AHRR cg05575921 hypomethylation, which has been previously linked to a range of pediatric and adult diseases.

Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator

BackgroundIn utero exposure to diabetes has been shown to contribute to preterm birth, though the underlying biological mechanisms are yet to be fully elucidated. Fetal epigenetic variations established in utero may be a possible pathway. This study aimed to investigate whether in utero exposure to diabetes was associated with a change in newborn DNA methylation, and whether the identified CpG sites mediate the association between diabetes and preterm birth in a racially diverse birth cohort population.MethodsThis study included 954 mother–newborn pairs. Methylation levels in the cord blood were determined using the Illumina Infinium MethylationEPIC BeadChip 850 K array platform. In utero exposure to diabetes was defined by the presence of maternal pregestational or gestational diabetes. Preterm birth was defined as gestational age at birth less than 37 weeks. Linear regression analysis was employed to identify differentially methylated CpG sites. Differentially methylated regions were identified using the DMRcate Package.Results126 (13%) newborns were born to mothers with diabetes in pregnancy and 173 (18%) newborns were born preterm, while 41 newborns were born both preterm and to mothers with diabetes in pregnancy. Genomic-wide CpG analysis found that eighteen CpG sites in cord blood were differentially methylated by maternal diabetes status at an FDR threshold of 5%. These significant CpG sites were mapped to 12 known genes, one of which was annotated to gene Major Histocompatibility Complex, Class II, DM Beta (HLA-DMB). Consistently, one of the two identified significant methylated regions overlapped with HLA-DMB. The identified differentially methylated CpG sites mediated the association between diabetes in pregnancy and preterm birth by 61%.ConclusionsIn this US birth cohort, we found that maternal diabetes was associated with altered fetal DNA methylation patterns, which substantially explained the link between diabetes and preterm birth.

PD18-03 THE EFFECTS OF PARENTAL-AGE DIFFERENCES ON ADVERSE PERINATAL OUTCOMES

You have accessJournal of UrologyCME1 Apr 2023PD18-03 THE EFFECTS OF PARENTAL-AGE DIFFERENCES ON ADVERSE PERINATAL OUTCOMES Victor Yu, Joemy Ramsay, Joshua John Horns, and James Hotaling Victor YuVictor Yu More articles by this author , Joemy RamsayJoemy Ramsay More articles by this author , Joshua John HornsJoshua John Horns More articles by this author , and James HotalingJames Hotaling More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003273.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The effects of advanced maternal age on perinatal outcomes have been well-documented, with several studies demonstrating a significant risk for women over 35 years. Other studies have identified potential associations between advanced paternal age and adverse perinatal outcomes. This study aimed to expand upon such findings by assessing the risks associated with the tertiary variable of parental-age differences. METHODS: A retrospective cohort analysis was performed using data compiled from the National Vital Statistics System for 21,021,091 US births between 2012-2018. Logistic regression controlling for demographic and health-related covariates was used to assess odds of low birthweight, very low birthweight, preterm birth, very preterm birth, small size for gestational age, low 5-minute APGAR score, congenital defects, and chromosomal anomalies. RESULTS: Increased parental-age differences were associated with significant risks for all adverse outcomes, aside from congenital defects, even when controlling for maternal age. Restricting maternal age to the reference range of 25-29 years, infants born to fathers aged 5-8 years younger (n=87,032) had 19% (OR 1.19, 95% CI 1.17 – 1.21) higher odds of having any adverse perinatal outcome. Conversely, infants born to fathers aged >16 years older (n=100,971) had 11% (OR 1.11, 95% CI 1.09 – 1.13) higher odds of having any adverse perinatal outcome. CONCLUSIONS: Large differences in parental age are associated with adverse birth outcomes and exhibit a bimodal distribution. Older mothers paired with younger fathers had the highest risks, even when maternal age was below 35 years. Potential mechanisms as to why younger fathers may elevate outcome risks include sperm genetic or epigenetic instability, lower socioeconomic status, unstable social and familial environments, or precarious lifestyle factors associated with this age group. Clinically, parental-age differences should be considered alongside maternal and paternal age when assessing risks of adverse perinatal outcomes for potential parents. Source of Funding: NIH Ruth L. Kirschstein National Research Service Award (NRS) institutional training grant (T35DK103596) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e503 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Victor Yu More articles by this author Joemy Ramsay More articles by this author Joshua John Horns More articles by this author James Hotaling More articles by this author Expand All Advertisement PDF downloadLoading ...