Birth Outcomes Among Women With Syphilis During Pregnancy in Six U.S. States, 2018-2021: Erratum.

The COVID-19 pandemic has substantially impacted the lives and health of people worldwide; with millions of confirmed cases and thousands of deaths, the immediate medical effects of the pandemic are obvious and substantial. However, the COVID-19 pandemic will likely continue to negatively impact human health for years to come, especially among individuals experiencing pandemic-related stress during sensitive periods of the life course, including pregnancy and early development. In this brief commentary, we focus on how the COVID-19 pandemic is currently disrupting maternity care and affecting well-being among pregnant women, thereby increasing the risk of poor future health for both mother and child. Human biologists have long been interested in understanding the pathways by which early life experience—including in utero—can impact future health outcomes (eg, metabolic and cardiovascular disease later in life), especially if experienced during key developmental periods (Kuzawa & Quinn, 2009). Pregnancy represents an especially vulnerable period, with women at an increased risk for developing mood disorders (eg, depression) and health conditions (eg, gestational diabetes, preeclampsia) that can impair longer-term mental and physical health (Bauer, Knapp, & Parsonage, 2016; Damm et al., 2016; Nahum Sacks et al., 2018). Moreover, evidence indicates that adverse conditions experienced during pregnancy—such as high levels of psychosocial stress—are linked with increased risk of negative birth outcomes (Aizer, Stroud, & Buka, 2016; Kinsella & Monk, 2009; Nepomnaschy et al., 2006; Pike, 2005; Thayer, Bécares, & Atatoa Carr, 2019). Cumulatively, these exposures can also increase the risk of poor offspring health (eg, elevated stress reactivity, higher body mass index, and greater chronic disease risk) and increased mortality risk across the life course (Dancause et al., 2015; Farewell, Thayer, Tracer, & Morton, 2018; Gluckman, Hanson, & Beedle, 2007; Thayer & Kuzawa, 2015). Elevated psychosomatic stress linked with the COVID-19 pandemic may therefore negatively impact maternal and infant health; however, these effects are currently not well understood. The few existing maternal and infant health studies have predominantly focused on treatment of pregnant women suffering from COVID-19 (Liang & Acharya, 2020; Pereira et al., 2020; Rasmussen, Smulian, Lednicky, Wen, & Jamieson, 2020), the risk of virus transmission from mother to baby (Chen et al., 2020; Pereira et al., 2020; Qiao, 2020; Rasmussen et al., 2020; Schwartz, 2020), and the biological effects of COVID-19 during pregnancy (Shanes et al., 2020). While there is currently little evidence of vertical viral transmission or poor birth outcomes (eg, restricted growth or premature birth) as a result of maternal SARS-CoV-2 infection (Pereira et al., 2020; Qiao, 2020; Schwartz, 2020; Shanes et al., 2020; Walker et al., 2020), recent work indicates that COVID-19 may be linked with increased risk for placental injury, preeclampsia, preterm birth, and low birth weight (Abbas, Ahmed, & Shaltout, 2020; Narang et al., 2020; Shanes et al., 2020). These emerging findings led the CDC to add pregnancy as a risk factor for severe COVID-19 symptoms on June 25, 2020 (CDC, 2020). However, given that most studies to date have been small and focused on immediate health outcomes, additional work is needed to understand how the pandemic may shape maternal and infant health, aside from the direct effects of the virus itself. A biocultural perspective will be especially important, as pandemic-related economic and social changes will likely shape prenatal and early life experiences in ways that alter later health. For example, the pandemic has drastically strained the American healthcare system (Emanuel et al., 2020). These strains have had substantial effects on access to quality prenatal care for pregnant women, an important determinant of maternal health and birth outcomes (Kozhimannil, Hardeman, & Henning-Smith, 2017; Loveland Cook, Selig, Wedge, & Gohn-Baube, 1999). A shift to telehealth appointments, the loss of in-person labor and delivery courses, and restrictions on the ability for support persons to attend prenatal appointments may prevent women from feeling well-informed and supported by their providers and others. In addition, crowded hospitals, overworked staff, and a lack of medical equipment have led to drastic changes in the experience of labor and delivery. These changes include reduced support persons in labor and, in some instances, separation of newborns from their mothers in the case of suspected or confirmed maternal COVID-19 status (Davis-Floyd, Gutschow, & Schwartz, 2020; de Carvalho et al., 2020). Yet the mental and physical health effects of COVID-19 associated maternity care changes have not been adequately addressed, despite the clear implications for maternal and infant well-being. Negative maternal and infant health outcomes linked with the pandemic are likely to disproportionally impact ethnic minority communities, including Black, Indigenous, and People of Color (BIPOC). For instance, COVID-19-associated disruptions to prenatal care, lack of access to the technology or safe spaces needed to facilitate telehealth, loss of medical insurance, and inability to access preferred and trusted care providers are all expected to increase the risk of poor birth outcomes and differentially affect BIPOC (Minkoff, 2020; Onwuzurike, Meadows, & Nour, 2020). Racism, which shapes birth experiences and outcomes even outside of the pandemic (Conching & Thayer, 2019; McLemore et al., 2018; Thayer et al., 2019; Vedam et al., 2019), can have important consequences on COVID-19-related policy decisions as well. In a particularly egregious instance documented in a piece of investigative journalism, women described as having a Native American "appearance" and who were found to be living in a zip code associated with one of New Mexico's Pueblo reservations were treated as a "person under investigation" for COVID-19 and separated from their newborns at birth if still awaiting COVID-19 test results, even when mothers exhibited no symptoms (Furlow, 2020). Maternal separation from newborns can negatively affect both maternal and newborn health, including temperature regulation for newborns, increased risk for postpartum depression for mothers, and decreased breastfeeding success (Stuebe, 2020). Additional work is needed to identify the different ways that the COVID-19 pandemic has differentially affected maternal and child health among socially disadvantaged groups. Here, we present the COVID-19 and Reproductive Effects (CARE) project as a case study documenting the complex COVID-19-linked factors impacting prenatal care and birth experiences. We also discuss other human biology studies that similarly use biocultural approaches to understand the impacts of the COVID-19 pandemic. Finally, we consider future research needed to document the downstream health effects of the COVID-19 pandemic on pregnant women and their children. The CARE study is a longitudinal study designed to evaluate how the pandemic has affected pregnant women's prenatal care decisions and birth experiences. Data are collected through an online survey administered to a convenience sample primarily recruited over social media (Facebook, Twitter), and distributed via email to contacts working in maternity care. Pregnant women over 18 years of age and living in the United States are eligible to participate. Prenatal questionnaires have been completed by over 2300 women, with 91% of women agreeing to be re-contacted for a follow-up postnatal questionnaire. Analyses using early respondents (n = 1400) found that 45.2% of participants anticipated altering some aspect of their birth plan because of COVID-19 (Gildner & Thayer, 2020). Commonly reported changes included shortened hospital stays, switching to an out-of-hospital delivery to avoid exposure to the virus in the hospital, and laboring with fewer support people (either due to hospital restrictions or the fact that their partner must now care for their other children instead of attending the delivery). Future analyses will determine how these planned changes impact birth outcomes. Aside from altering birth plans, preliminary evidence suggests the pandemic is impacting maternal mental health. For instance, pandemic-related financial stress was significantly associated with increased depression symptoms and increased likelihood of a clinically significant depression score, as measured by the well-validated Edinburgh Postnatal Depression Scale. These effects remained after adjusting for covariates, including household income, suggesting that financial stress caused by the COVID-19 pandemic may increase depression symptoms in pregnancy, which could impact birth outcomes and long-term offspring health (Thayer & Gildner, 2020a). In addition to measuring how the pandemic is affecting maternity care access and depression risk, an overarching goal of the CARE study is to develop educational handouts based on study results for participants, care providers, and policy makers. For example, study results indicate that 40% of participants reported not having received any information from their provider on how the pandemic would influence their maternity care in pregnancy, labor, and delivery (including 25% in their third trimester of pregnancy). Women who were less educated and who had lower income were significantly less likely to report having received information about how the pandemic would affect their care. A reported lack of provider information sharing was associated with significantly lower satisfaction with provider (Thayer & Gildner, 2020b). In response to this lack of reported information sharing, we created a handout outlining unanswered COVID-19-related care questions commonly reported by women in the prenatal study questionnaire. This handout is designed to serve as a conversation starting point, facilitating more productive communication between women and their care providers. It was disseminated through the same virtual means as participant recruitment and posted to our study website. Given the urgency of the moment, we have approached disseminating study findings to participants as being of utmost importance. Information sharing is crucial to provide individuals with the information needed to make informed decisions regarding behavioral responses and medical care during the COVID-19 pandemic. Building upon this preliminary work, future analyses are planned to examine how the COVID-19 pandemic affected birth experiences and outcomes, as well as which socioeconomic and geographic factors most strongly influence whether women are able to access preferred providers and delivery facilities during the pandemic. Additional analyses will also explore shifting social attitudes toward maternity care norms, including altered preferences (eg, for out-of-hospital deliveries) that may persist beyond the pandemic. Assessment of minimally-invasive biomarkers from children enrolled in the study is also planned in order to understand some of the longer term biological effects of COVID-19-associated stressors. Overall, the results produced by this project can be used in conjunction with existing and future data from other sources to tease apart the myriad pandemic-related factors that influence maternal and infant health. While the CARE study highlights some potential ways that the COVID-19 pandemic may negatively impact maternal and child health, it is by no means the only project using a biocultural approach to understand the health impacts of the pandemic. Given the scope of the unfolding pandemic, no single study can capture every lived experience and health outcome directly linked with the social, political, and economic damage caused by COVID-19. A wide array of studies using diverse data collection and analysis techniques are needed to better understand the full extent of COVID-19-related maternal and child health effects. Fortunately, several human biologists have launched studies documenting the effects of the ongoing pandemic on maternal and child health. The data collected by these projects will highlight how the pandemic has shaped various aspects of prenatal care, birth experiences, breastfeeding practices, and early development. Table 1 highlights some of these projects, including a description of the study sample, type of data collected, and research foci. Cumulatively, each of these projects will contribute novel information to the growing dataset required to holistically examine the complex health effects of the pandemic. Ideally collaboration among studies will facilitate a more comprehensive understanding of long-term pandemic impacts. Studies in outside the United States are also needed to measure the full range of pandemic-related effects on maternal and infant health. While the immediate medical impacts of COVID-19 are important to understand, it is becoming increasingly clear that this pandemic will also exert long-term social and economic effects that will shape health outcomes for years to come. A biocultural perspective is needed to clarify how the lived experience of the COVID-19 pandemic, coupled with anticipated lifestyle changes due to a destabilized economy and shifts in cultural practices, may shape later health. Longitudinal cohort studies monitoring maternal and child health over time are required. These data will document the cross-cultural and intergenerational effects of COVID-19, as well as clarify how the pandemic has differentially affected certain groups (eg, socioeconomically and ethnically marginalized groups) within a given population. By tracking prenatal stressors, birth outcomes, and developmental patterns, researchers can assess the effects of the pandemic on later health. Additionally, immediate or later collection of anthropometric measures and biomarker samples—in a way that maintains participant and researcher safety—may provide another important data source. For example, measures of child growth and stress reactivity can be used to test how prenatal and early postpartum experiences during the pandemic shape growth patterns and development of the physiological stress response, which are predicted to be affected by early life exposures and may influence future disease risk (Dancause et al., 2015; Thayer, Wilson, Kim, & Jaeggi, 2018). The collection of these data across diverse populations will help us to understand how the COVID-19 pandemic has acted across different socioeconomic, ecological, and cultural contexts to shape lived experience and health. However, for the time being, ethical concerns regarding travel during the pandemic will appropriately limit data collection to field settings where remote data collection (eg, online or mailed survey and sample collection) is feasible. Ultimately, the varied toolkit of human biology is well suited to collect these important data and to answer questions related to the impact of the pandemic on long-term well-being, information needed to better address the continuing consequences of the COVID-19 pandemic and to prepare for the effects of other future global health challenges. Theresa Gildner: Conceptualization; writing-original draft; writing-review and editing. Zaneta Thayer: Conceptualization; writing-original draft; writing-review and editing.

BackgroundThere is lack of information about the effect of general distress and pregnancy-specific distress in mid- and late-pregnancy separately on neonatal outcome.ObjectiveThe aim of this study was to assess the effects of mid-maternal distress on late-maternal distress and birth outcomes with a causal model of relationships among general distress and pregnancy-specific distress.Materials and MethodsIn this longitudinal descriptive study, 100 low-risk pregnant women participated. Participants completed three questionnaires at mid-pregnancy (13–26 wk) and at late pregnancy (27–40 wk). Pregnancy-general distress was assessed by the Perceived Stress Scale and the Hospital Anxiety Depression Scale. Pregnancy-specific distress was evaluated by the Prenatal Distress Questionnaire. The pregnant women were followed to after birth and neonatal outcome were assessed.ResultsAll total effect pathways were significant as predictors of birth outcomes (height, weight, and head circumference). Mid-pregnancy-specific distress had a significant relationship with late pregnancy-specific distress. However, mid-maternal distress was not related directly to birth outcomes. The effect of mid-maternal distress on birth outcomes was related indirectly to late-maternal distress. Both late general distress and late pregnancy-specific distress had direct negative effects on three indexes of birth outcome. The negative effect of late general-pregnancy distress and mid-pregnancy-specific distress on birth outcome was mediated through late pregnancy-specific distress.ConclusionBoth late pregnancy-general distress and pregnancy-specific distress have negative effects on birth outcomes. These findings support a role for negative effect as mediating the relationship between late pregnancy-specific distress and birth outcomes.

The Association Between Childhood Abuse and Neglect and Clinical Severity in Mood Disorders

BackgroundAntenatal maternal psychological distress is common in low and middle-income countries (LMIC), but there is a dearth of research on its effect on birth and developmental outcomes in these settings, particularly in Sub-Saharan Africa. This study set out to identify risk factors for antenatal maternal psychological distress and determine whether antenatal maternal psychological distress was associated with infant birth and developmental outcomes, using data from the Drakenstein Child Health Study (DCHS), a birth cohort study in South Africa. MethodsPregnant women were enrolled in the DCHS from primary care antenatal clinics. Antenatal maternal psychological distress was measured using the Self-Reporting Questionnaire 20-item (SRQ-20). A range of psychosocial measures, including maternal childhood trauma, depression, and posttraumatic stress disorder (PTSD) were administered. Birth outcomes, including premature birth, weight-for-age z-score and head circumference-for-age z-score, were measured using revised Fenton growth charts. The Bayley III Scales of Infant and Toddler Development was administered at 6 months of age to assess infant development outcomes, including cognitive, language, and motor domains in a subset of n=231. Associations of maternal antenatal psychological distress with psychosocial measures, and with infant birth and developmental outcomes were examined using linear regression models. Results961 women were included in this analysis, with 197 (21%) reporting scores indicating the presence of psychological distress. Antenatal psychological distress was associated with maternal childhood trauma, antenatal depression, and PTSD, and inversely associated with partner support. No association was observed between antenatal maternal psychological distress and preterm birth or early developmental outcomes, but antenatal maternal psychological distress was associated with a smaller head circumference at birth (coefficient=−0.30, 95% CI: −0.49; −0.10). ConclusionAntenatal maternal psychological distress is common in LMIC settings and was found to be associated with key psychosocial measures during pregnancy, as well as with adverse birth outcomes, in our study population. These associations highlight the potential value of screening for antenatal maternal psychological distress as well as of developing targeted interventions.

A national survey of Australian midwives’ birth choices and outcomes

Maternal vitamin D status during pregnancy has been associated with infant birth and postnatal growth outcomes, but reported findings have been inconsistent, especially in relation to postnatal growth and adiposity outcomes. In a mother-offspring cohort in Singapore, maternal plasma vitamin D was measured between 26 and 28 weeks of gestation, and anthropometric measurements were obtained from singleton offspring during the first 2 years of life with 3-month follow-up intervals to examine birth, growth and adiposity outcomes. Associations were analysed using multivariable linear regression. Of a total of 910 mothers, 13·2 % were vitamin D deficient (<50 nmol/l) and 26·5 % were insufficient (50-75 nmol/l). After adjustment for potential confounders and multiple testing, no statistically significant associations were observed between maternal vitamin D status and any of the birth outcomes - small for gestational age (OR 1·00; 95 % CI 0·56, 1·79) and pre-term birth (OR 1·16; 95 % CI 0·64, 2·11) - growth outcomes - weight-for-age z-scores, length-for-age z-scores, circumferences of the head, abdomen and mid-arm at birth or postnatally - and adiposity outcomes - BMI, and skinfold thickness (triceps, biceps and subscapular) at birth or postnatally. Maternal vitamin D status in pregnancy did not influence infant birth outcomes, postnatal growth and adiposity outcomes in this cohort, perhaps due to the low prevalence (1·6 % of the cohort) of severe maternal vitamin D deficiency (defined as of <30·0 nmol/l) in our population.

BackgroundAntenatal depression is associated with intrauterine growth retardation, preterm birth, and low birth weight. Infants born to mothers with postnatal depression also may suffer from malnutrition and other health problems. Even though there are few single studies conducted so far, a systematic review of these studies is highly important to highlight the effect of antenatal and perinatal depression on adverse birth and infant health outcomes in Africa.MethodsWe used the Preferred Report Items for Systematic Review and Meta-analysis (PRISMA) when conducting this study. Databases like CINAHL (EBSCO), MEDLINE (via Ovid and PubMed), PsycINFO, Emcare, Psychiatry Online, and Scopus were searched. In addition, Google Scholar and references from a list of eligible studies were explored. We included good quality observational studies based on Newcastle Ottawa Scale which are published in the English language between 2007 and 2018. Heterogeneity and publication bias were assessed. Meta-analysis with a random effect model was employed to determine the pooled effect sizes with a 95% confidence interval. The review protocol is registered in PROSPERO (CRD42018106714).ResultWe found three studies (1511 participants) and 11 studies (22,254 participants) conducted on the effect of antenatal depression on birth outcomes and perinatal depression on adverse infant health outcomes, respectively. The overall risk of having adverse birth outcomes was 2.26 (95% CI: 1.43, 3.58) times higher among pregnant mothers with depression. The risk of preterm birth and low birth weight was 1.77 (95% CI: 1.03, 3.04) and 2.98 (95% CI: 1.60, 5.55) respectively. Similarly, the risk of having adverse infant health outcomes namely malnutrition and febrile illness was 1.61 (95% CI: 1.34, 1.95) times higher among mothers who had perinatal depression.ConclusionsWe have found a significant association between antenatal depression and adverse birth outcomes, low birth weight and preterm birth. Similarly, a significant effect of perinatal depression on adverse infant health outcomes namely, malnutrition, and febrile illnesses was observed. The findings highlight that it is time to integrate mental health services with routine maternal health care services to improve birth outcomes and reduce infant morbidity.

Adversity and risk of poor birth and infant outcomes for young mothers: a population-based data-linkage cohort study

Preconception exposures have been associated with adverse pregnancy, birth and postpartum outcomes. However, the reports, statements and guidelines of national and international health organisations vary in what they recommend individuals should monitor, avoid, reduce or practise in the preconception period. To synthesise and evaluate the evidence across systematic reviews for associations between exposures before conception and adverse pregnancy, birth and postpartum outcomes. MEDLINE, Embase, Epistemonikos (to May 2020) and reference lists of included reviews, without language or date restrictions. Systematic literature reviews of observational and/or interventional studies reporting associations between preconception exposures in women and/or men of reproductive age and pregnancy, birth or postpartum health outcomes were included. The methodological quality of reviews and the certainty of the evidence underlying each exposure-outcome association were assessed using AMSTAR 2 and the GRADE approach. We identified 53 eligible reviews reporting 205 unique exposure-outcome associations. Methodological quality was generally low with only two reviews rated as 'high' quality and two as 'moderate'. We found high-certainty, randomised trial evidence that maternal folate supplementation reduces the risk of neural tube defects and anomaly-related terminations. Moderate-certainty, observational evidence was found that maternal physical activity is associated with reduced risk of pre-eclampsia and gestational diabetes, and that paternal age of ≥40years and maternal body mass index (BMI) and interpregnancy weight gain are associated with increased risk of various adverse pregnancy and birth outcomes. Low- and very low-certainty evidence was found for other associations. Clinicians and policymakers can be confident that maternal folate supplementation should be encouraged during the preconception period. There is moderate certainty in the evidence base that maternal physical activity, BMI and interpregnancy weight gain and advanced paternal age are important preconception considerations. High-quality research is required to better understand other exposure-outcome associations.

Based in Allegheny County, a coalition of local stakeholders took note of the region's infant mortality rates, particularly the stark disparities observed by race, and established a vision to reduce infant mortality in the region. The group undertook a multi-faceted effort to (1) develop predictive models of infant mortality risk; (2) evaluate the effectiveness of available interventions; and (3) combine these tools in order to tailor intervention referrals based on maternal risk profiles. With this effort, the coalition sought to address the apparent disconnect between the region's robust maternal and child health care system and relatively poor birth and infant outcomes and racial disparities. The effort started with the integration of data from a variety of sources into an integrated database built specifically for this research effort covering the period 2003 to 2013. With the database, researchers linked each individual's data across multiple data sources, including the Allegheny County Health Department, the University of Pittsburgh Medical Center, the Allegheny County Department of Human Services Data Warehouse, and individual programs. With these data, we used a standard method for comparing outcomes and measuring the racial disparity between Black and white infants that involved calculating a ratio by dividing the rate or percentage for Black infants by the rate or percentage for white infants. Overall, the results showed that between 2003 and 2013 in Allegheny County disparities were more pronounced for infant mortality (3.25) than low birthweight (1.88) or preterm birth (1.49). Among the different potential causes of infant mortality, the most pronounced disparity was for SIDS (1.78). Among maternal health factors, pre-pregnancy obesity and gestational diabetes had the highest infant mortality disparity. The low birthweight disparity was similar and lower than the infant mortality disparity across all of the maternal health factors, while the preterm birth disparity was even lower. For the maternal behavioral and contextual factors, the infant mortality disparity ranged from 1.5 to 2.3. The 11-year span of data reported in the IMPreSIv database and the breadth of intervention data included allowed us to report granular information on birth outcomes within Allegheny County over this time period. The database also allowed us to summarize the various factors associated with the range of birth outcomes and describe the participation rates in the medical and community setting interventions. Against this backdrop of pronounced disparities in birth outcomes across a range of factors, we examined the effectiveness of interventions for women with different risk factors (e.g. substance use disorders) in order to develop a tool to facilitate individualized referrals to the interventions that will help the most for a specific risk profile.

Exposure to fine particulate matter (PM2.5) has been linked with several adverse birth and reproductive outcomes, including preterm birth and low birthweight.1 These adverse outcomes are important to investigate, given that they are predictors of infants’ risk of short- and long-term morbidity and mortality, as well as maternal and family stress.1, 2 In this issue of Paediatric and Perinatal Epidemiology, two articles explored the relationships between ambient air pollution exposures and preterm birth. Although they investigated the same outcome, the research questions were different. Costello et al.3 assessed whether living close to major roads was associated with preterm birth in California. By linking birth certificate and hospital discharge data, they were able to adjust for many risk factors with large and diverse populations. They did not find any adverse relationships for preterm birth with the traffic measures but found associations with PM2.5 and diesel PM, using summarised data obtained from CalEnviroScreen. In contrast, Ha and colleagues investigated the associations between short-term exposure to PM2.5 and ozone (O3) and preterm birth in the San Joaquin Valley, California, using a time-stratified case-crossover design.4 A strength of using this study design is that adjusting for time-invariant factors, such as race/ethnicity, was not necessary in the statistical analysis. They found that PM2.5 exposures at lag 5 and at lags 5–7 were associated with very preterm birth (gestational age <34 weeks) and early term birth (gestational age between 37 and 39 weeks), respectively, but associations were not found for preterm birth at any lags. O3 exposure was associated with very preterm birth, preterm and early term birth at lags 4–7, lags 2 and 4–7 and lags 0–7, respectively. Notably, the two studies used different types of exposure data. The San Joaquin Valley study modelled pollutant levels at the zip code level by combining ground-level monitors and Community Multiscale Air Quality (CMAQ) models, while Costello et al. used traffic metrics and ambient ground monitors, whose values were transformed to CalEnviroScreen. Modelled data are becoming more commonly used in environmental epidemiology because they may reduce exposure misclassification or enable exposure data in areas where monitors are scarce, particularly for people living in suburban and rural areas. Ambient ground monitors are still important, especially because some of them use Federal Reference Method, which is regarded as the gold standard of air pollution measurements and are essential for calibrating simulated or satellite data.5 Because some of the modelled data are publicly available,6 more studies are likely to utilise these data in the future. Health data, however, may not be available at the same fine resolution as the exposure data, as residential zip code or the census tract data are typically the finest level of aggregation for analyses. Moreover, most of data do not incorporate daily time-activity patterns, and exposure is primarily based on residential zip code, resulting in further exposure misclassification. Thus, validation studies comparing the effect estimates between those that have used residential exposures and zip code level exposure data as well as considering time-activity patterns are warranted to address these data gaps. Another notable contrast between the two studies was the exposure windows. Costello et al.3 considered non-temporal traffic metrics (i.e., living near major roads, traffic density and traffic volume) as well as long-term exposure (i.e., the mean of three annual PM2.5 averages from 2012 to 2014 and diesel PM in 2012). This approach implies that they looked at spatial contrasts in the analyses. Because of several factors, such as standard regulations, emission patterns, ambient temperature and heights of the boundary layer, PM2.5 levels vary by season and year. Variables lacking temporal contrast, such as living near roads, may not reflect PM2.5 variation accurately and contribute to the lack of associations with preterm birth. Nevertheless, they found some associations between preterm birth and the summary measurement of PM2.5 and diesel PM, from community mapping tools, indicating that places with higher levels of PM2.5 have greater risk for preterm birth. In contrast, Ha et al.4 focused on short-term pollutant exposures with lags up to seven days. The heterogeneous results by lag days indicated that exposure to PM2.5 or O3 is time-sensitive, but it is unclear why some specific lag days had positive associations with very preterm birth, whereas earlier lags (e.g., lag 1) did not. Furthermore, the study period was limited to the warm season for O3 and the cool season for PM2.5, limiting the generalisability of the findings to the whole year. Regardless of the differences, these PM2.5 studies have several implications not only for preterm birth, but also for other adverse birth outcomes literatures including low birthweight and stillbirth.1, 7 First, identifying relevant exposure windows is important. Because each outcome has unique biological mechanisms, the relevant exposure windows likely vary. It is particularly important to research very short-term exposure, such as within 24 h (sub-daily exposures) prior to labour and delivery because few studies have explored this window.2 Second, as an alternative to the traffic metrics, collecting PM2.5 chemical composition or source apportionment data may help reveal toxic emission sources.7 Third, a more sophisticated statistical model is needed to identify those windows rather than applying non-temporal or single lag models. Applying distributed lag non-linear models or Gaussian process models, for example, might help show smoothed effects over time.8, 9 Lastly, further toxicological studies are needed to gain more insight into the potential biological mechanisms of these findings. Inhalation of PM2.5 may cause systemic inflammation or oxidative stress, triggering preterm birth,2, 10 but it is unclear which exposure windows are particularly relevant in these mechanisms. The Integrated Science Assessment for Particulate Matter by the U.S. EPA stated that selecting the relevant exposure window is a major issue in studying the relationship between PM2.5 and reproductive and developmental effects and concluded that the evidence is suggestive of a causal relationship.2 Further investigations are encouraged on this topic with access to various types of birth data, modelled exposure data with fine resolution and novel statistical methods to identify relevant exposure windows. The contents in this article are solely those of the authors, and do not necessarily represent those of the California Environmental Protection Agency, the Office of Environmental Health Hazard Assessment, or the State of California. Keita Ebisu and Rupa Basu co-drafted the paper. None. Keita Ebisu is an environmental epidemiologist of the Air and Climate Epidemiology Section at the Office of Environmental Health Hazard Assessment of the California Environmental Protection Agency. His primary research interest is evaluating effects of environmental exposures on children’s health, including birth outcomes. He has multiple publications on the effects of fine particulate matter and its sources on birth outcomes. Rupa Basu is the Chief of the Air and Climate Epidemiology Section at the Office of Environmental Health Hazard Assessment of the California Environmental Protection Agency. She has extensive experience relating to the associations between temperature and air pollution on mortality, morbidity, and adverse birth outcomes. She serves on several statewide and national climate change committees and has received a lot of media attention for her work, including interviews from The New York Times, The New Yorker, The San Francisco Chronicle, the LA Times, and NPR. Dr. Basu serves on the Editorial Board of Paediatric and Perinatal Epidemiology. Data are not used in this article.

Prevalence of migraine is high during the reproductive age. Although migraine often improves during pregnancy, the risk of adverse pregnancy, birth, neonatal, and neurological outcomes in mother and offspring remains poorly understood. To investigate the associations between maternal migraine and risks of adverse pregnancy outcomes in the mother, and birth, neonatal and postnatal outcomes in the offspring. We used Danish population registries to assemble a cohort of pregnancies among women with migraine and an age- and conception year-matched comparison cohort of pregnancies among women without migraine. The study period was 2005-2012. We computed adjusted prevalence ratios (aPRs) for pregnancy and birth outcomes and adjusted risk ratios (aRRs) for neonatal and postnatal outcomes, adjusting for age, preconception medical history, and preconception reproductive history. We identified 22,841 pregnancies among women with migraine and 228,324 matched pregnancies among women without migraine. Migraine was associated with an increased risk of pregnancy-associated hypertension disorders (aPR: 1.50 [95% confidence interval (CI): 1.39-1.61]) and miscarriage (aPR: 1.10 [95% CI: 1.05-1.15]). Migraine was associated with an increased prevalence of low birth weight (aPR: 1.14 [95% CI: 1.06-1.23]), preterm birth (aPR: 1.21 [95% CI: 1.13-1.30]) and cesarean delivery (aPR: 1.20 [95% CI: 1.15-1.25]), but not of small for gestational age offspring (aPR: 0.94 [95% CI: 0.88-0.99]) and birth defects (aPR: 1.01 [95% CI: 0.93-1.09]). Offspring prenatally exposed to maternal migraine had elevated risks of several outcomes in the neonatal and postnatal period, including intensive care unit admission (aRR: 1.22 [95% CI: 1.03-1.45]), hospitalization (aRR: 1.12 [95% CI: 1.06-1.18]), dispensed prescriptions (aRR: 1.34 [95% CI: 1.24-1.45]), respiratory distress syndrome (aRR: 1.20 [95% CI: 1.02-1.42]), and febrile seizures (aRR: 1.27 [95% CI: 1.03-1.57), but not of death (aRR: 0.67 [95% CI: 0.43-1.04]) and cerebral palsy (aRR: 1.00 [95% CI: 0.51-1.94]). Women with migraine and their offspring have greater risks of several adverse pregnancy outcomes than women without migraine.

BACKGROUNDFew population-based data exist on birth outcomes in women who received opioid maintenance treatment during pregnancy. We therefore examined adverse birth outcomes in women exposed to methadone or buprenorphine during pregnancy and the risk of neonatal abstinence syndrome (NAS) among neonates exposed to buprenorphine, methadone, and/or heroin in utero.PATIENTS AND METHODSThis study included all female Danish residents with a live birth or a stillbirth from 1997 to 2011. We identified the study population, use of opioids and opioid substitution treatment, birth outcomes, and NAS through medical registers. Birth outcomes included preterm birth (born before 38th gestational week), low-birth weight (LBW) (<2,500 g, restricted to term births), small for gestational age (SGA) (weight <2 standard deviations from the sex- and gestational-week-specific mean), congenital malformations, and stillbirths. We used log-binomial regression to estimate the prevalence ratio (PR) for birth outcomes.RESULTSAmong 950,172 pregnancies in a total of 571,823 women, we identified 557 pregnancies exposed to buprenorphine, methadone, and/or heroin (167 to buprenorphine, 197 to methadone, 28 to self-reported heroin, and 165 to combinations). Compared with nonexposed pregnancies, prenatal opioid use was associated with greater prevalence of preterm birth (PR of 2.8 (95% confidence interval (CI), 2.3–3.4)), LBW among infants born at term (PR of 4.3 (95% CI, 3.0–6.1)), and being SGA (PR of 2.7 (95% CI, 1.9–4.3)). Restricting the analyses to women who smoked slightly lowered these estimates. The prevalence of congenital malformations was 8.3% in opioid-exposed women compared with 4.2% in nonexposed women (PR of 2.0 (95% CI, 1.5–2.6)). The risk of NAS ranged from 7% in neonates exposed to buprenorphine only to 55% in neonates exposed to methadone only or to opioid combinations.CONCLUSIONThe maternal use of buprenorphine and methadone during pregnancy was associated with increased prevalence of adverse birth outcomes, and this increase could only be explained to a smaller extent by increased prevalence of smoking. The risk of NAS was eight-fold higher in methadone-exposed neonates than that in buprenorphine-exposed neonates, but this difference may at least partly be explained by differences in underlying indications (analgesic versus opioid maintenance treatment) between the two groups.

BackgroundThe influence of maternal levothyroxine treatment during pregnancy remains unclear. This study aimed to evaluate the associations of maternal levothyroxine treatment during pregnancy with the birth and neurodevelopmental outcomes in offspring.MethodsThis population-based cohort study was conducted among pregnant women using the Hong Kong Clinical Data Analysis and Reporting System. Mother-child pairs in Hong Kong from 2001 to 2015 were included and children were followed up till 2020. We defined the exposure group as mothers who were exposed to levothyroxine during pregnancy. Preterm birth and small for gestational age (SGA) were included as birth outcomes. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) were included as neurodevelopmental outcomes. Odds ratios (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) were evaluated to assess the association of gestational levothyroxine use with offspring birth and neurodevelopmental outcomes respectively, using propensity score fine-stratification weighting and a Cox proportional hazards regression model.ResultsAmong 422,156 mother-child pairs, 2125 children were born from mothers exposed to levothyroxine during pregnancy. A significantly increased risk of preterm birth was observed in children with maternal levothyroxine exposure during pregnancy, when compared to mothers who had no history of thyroid-related diagnoses or prescriptions (weighted OR [wOR]: 1.22, 95% CI: 1.07, 1.39). Similarly, an increased risk of preterm birth was found among children of gestational levothyroxine users, when compared to children of mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16, 95% CI: 1.09, 4.25). Sensitivity analysis, by excluding mothers exposed to psychotropic or antiepileptic medications before or during pregnancy, also indicated a similar increased risk of preterm birth regarding the gestational use of levothyroxine (wOR: 1.26, 95% CI: 1.10, 1.45). No significant association was observed for the risk of SGA, ADHD, and ASD.ConclusionsThere is no evidence that gestational use of levothyroxine is associated with SGA, ADHD, or ASD in offspring. Gestational levothyroxine treatment is associated with a higher risk of preterm birth. Such risk might be confounded by the underlying maternal thyroid disease itself, however, we cannot completely exclude the possible effect of gestational L-T4 treatment on offspring preterm birth. Our findings provided support to the current guidelines on the cautious use of levothyroxine treatment during pregnancy.

BackgroundMaternal age is increasingly recognized as a predictor of birth outcomes. Given the importance of birth and growth outcomes for children’s development, wellbeing and survival, this study examined the effect of maternal age on infant birth and growth outcomes at 6 months and mortality. Additionally, we conducted quantitative bias analysis (QBA) to estimate the role of selection bias and unmeasured confounding on the effect of maternal age on infant mortality.MethodsWe used data from randomized–controlled trials (RCTs) of 21 555 neonates in Burkina Faso conducted in 2019–2020. Newborns of mothers aged 13–19 years (adolescents) and 20–40 years (adults) were enrolled in the study 8–27 days after birth and followed for 6 months. Measurements of child’s anthropometric measures were collected at baseline and 6 months. We used multivariable linear regression to compare child anthropometric measures at birth and 6 months, and logistic regression models to obtain the odds ratio (OR) of all-cause mortality. Using multidimensional deterministic analysis, we assessed scenarios in which the difference in selection probability of adolescent and adult mothers with infant mortality at 6 months increased from 0% to 5%, 10%, 15% and 20% if babies born to adolescent mothers more often died during the first week or were of lower weight and hence were not eligible to be included in the original RCT. Using probabilistic bias analysis, we assessed the role of unmeasured confounding by socio-economic status (SES).ResultsBabies born to adolescent mothers on average had lower weight at birth, lower anthropometric measures at baseline, similar growth outcomes from enrolment to 6 months and higher odds of all-cause mortality by 6 months (adjusted OR = 2.17, 95% CI 1.35 to 3.47) compared with those born to adult mothers. In QBA, we found that differential selection of adolescent and adult mothers could bias the observed effect (OR = 2.24, 95% CI 1.41 to 3.57) towards the null [bias-corrected OR range: 2.37 (95% CI 1.49 to 3.77) to 2.84 (95% CI 1.79 to 4.52)], whereas unmeasured confounding by SES could bias the observed effect away from the null (bias-corrected OR: 2.06, 95% CI 1.31 to 2.64).ConclusionsOur findings suggest that delaying the first birth from adolescence to adulthood may improve birth outcomes and reduce mortality of neonates. Babies born to younger mothers, who are smaller at birth, may experience catch-up growth, reducing some of the anthropometric disparities by 6 months of age.