Daily snuff use during pregnancy, gestational length and birth weight; register-based study.

BACKGROUND: Snuff is a smokeless source of nicotine that is common in Scandinavia and increasingly used by women of fertile age. Persistent use of snuff during pregnancy has been associated with adverse pregnancy outcomes. Emerging data from the Medical Birth Registry of Norway distinguishes between occasional use and daily use. We provide preliminary estimates of associations between frequency of snuff and gestational length and birth weight. METHODS: Data on snuff use during pregnancies delivered in 2020 and 2021 were available for the west and central regions of Norway. Associations of snuff use with gestational length and birth weight at term (39-41 weeks) were estimated using quantile regression at the 25th, the 50th and the 75th percentiles, with adjustments for mother's age, pre-pregnancy weight, and parity. We compared associations with the pregnancy outcomes according to maternal snuff and cigarette use. RESULTS: 12.4% of 18 042 non-smoking women reported daily use of snuff before pregnancy, and 4.6% reported continuing use during pregnancy, with 1.2% still reporting daily use in the last trimester. Women with daily use through the last trimester delivered babies with a median gestational length reduced by 3.4 days (95% CI: -5.0 to -1.7 days) compared with women who never used snuff. The reduction was even stronger at the 25th percentile of gestational age. The median term birth weight was reduced by 44 g (95% CI: -134 to 46 g). These associations were much weaker for women who quit snuff at some point during pregnancy or used snuff only occasionally. Mothers who smoked daily through the last trimester had a median gestational length reduced by 2.1 days (95% CI: -2.7 to -1.4) and a median term birth weight reduced by 294 g (95% CI: -325 to -262) compared with never-smokers. CONCLUSIONS: Daily snuff use through the last trimester reduced the median gestational length by more than three days. Snuff reduced birth weight, but not as much as smoking, suggesting that the predominant effect of smoking on fetal growth is not through nicotine but through the additional toxic chemicals in cigarettes or by reduced oxygen supply to the fetus.

Predictive value of Vitamin D levels in pregnant women on gestational length and neonatal weight in China: a population-based retrospective study.

BACKGROUND: Vitamin D deficiency, a common occurrence among pregnant women, is an emerging public health concern worldwide. According to research, prenatal vitamin D deficiency is associated with various complications. This study assessed the vitamin D status of pregnant women in Yanbian, Jilin Province, as well as the correlation and predictive value of their vitamin D levels in relation to gestational length (weeks) and fetal weight, aiming to provide a basis for clinical diagnosis and treatment. METHODS: We conducted a population-based retrospective study involving 510 pregnant women from August 2019 to October 2022. Blood samples were collected at 16-20 weeks of gestation for the detection of serum vitamin D levels. Statistical analyses were performed using SPSS 28.0 and R 4.1.0 software. Multifactorial logistic regression analysis was employed to establish whether each variable was a risk factor for deliveries at ≤ 38 gestational weeks and low fetal weight. These results were used to construct a risk prediction model, and the model's predictive efficacy was evaluated. Results or differences with p < 0.05 were considered statistically significant. RESULTS: Multifactorial logistic regression analysis revealed that vitamin D ≤ 14.7 ng/mL(OR: 1.611; 95% CI: 1.120-2.318; P = 0.010), Bone Mineral Density (BMD) T-value ≤-1(OR: 1.540; 95%CI: 1.067-2.223; P = 0.021), and gestational hypertension(OR: 7.173; 95% CI: 1.482-34.724; P = 0.014) were the independent risk factors for deliveries at ≤ 38 gestational weeks. Additionally, vitamin D ≤ 14.7 ng/mL(OR: 1.610; 95%CI: 1.123-2.307; P = 0.009), BMD T-value ≤ -1(OR: 1.560; 95%CI: 1.085-2.243; P = 0.016), and gestational hypertension(OR: 4.262; 95% CI: 1.058-17.167; P = 0.041) were the independent risk factors for low fetal weight (< 3400 g). CONCLUSION: This study revealed that low vitamin D levels are an independent risk factor for a short gestational length and low fetal weight. Prenatal low BMD T-value and comorbid hypertensive disorders were also found to increase the risk of a short gestational length and low fetal weight.

The effect of birth timing manipulation around carnival on birth indicators in Brazil.

This paper studies the patterns and consequences of birth timing manipulation around the carnival holiday in Brazil. We document how births are displaced around carnival and estimate the effect of displacement on birth indicators. We show that there is extensive birth timing manipulation in the form of both anticipation and postponement that results in a net increase in gestational length and reductions in neonatal and early neonatal mortality, driven by postponed births that would otherwise happen through scheduled c-sections. We also find a reduction in birthweight for high-risk births at the bottom of the weight distribution, driven by anticipation. Therefore, restrictions on usual delivery procedures due to the carnival holiday can be both beneficial and detrimental, raising a double-sided issue to be addressed by policymakers.

Interrogating Components of 2 Diet Quality Indices in Pregnancy using a Supervised Statistical Mixtures Approach.

BACKGROUND: The Healthy Eating Index (HEI)-2015 and Alternative Healthy Eating Index (AHEI)-2010 evaluate diet holistically in pregnancy. However, it remains unclear how individual index components interact to contribute to health. OBJECTIVES: To evaluate associations of HEI-2015 and AHEI-2010 components with gestational length using traditional and novel statistical methods in a prospective cohort. METHODS: Pregnant women completed a 3-mo food-frequency questionnaire (FFQ) at median 13 wk gestation to calculate the HEI-2015 or AHEI-2010. Covariate-adjusted linear regression models evaluated associations of HEI-2015 and AHEI-2010 total scores and individual components (one at a time and simultaneously adjusted) with gestational length. Covariate-adjusted weighted quantile sum regression models evaluated 1) associations of HEI-2015 or AHEI-2010 components as mixtures with gestational length and 2) contributions of components to these associations. RESULTS: Each 10-point increase in HEI-2015 and AHEI-2010 total score was associated with 0.11 (95% CI: -0.05, 0.27) and 0.14 (95% CI: 0.00, 0.28) wk longer gestation, respectively. In individual or simultaneously adjusted HEI-2015 models, higher intakes of seafood/plant proteins, total protein foods, greens/beans, and saturated fats but lower intakes of added sugars and refined grains were associated with longer gestational length. For the AHEI-2010, higher intake of nuts/legumes and lower intake of sugar-sweetened beverages (SSBs)/fruit juice were associated with longer gestational length. Jointly, 10% increases in HEI-2015 or AHEI-2010 mixtures were associated with 0.17 (95% CI: 0.001, 0.34) and 0.18 (95% CI: 0.05, 0.30) wk longer gestational length, respectively. Seafood/plant protein, total protein foods, dairy, greens/beans, and added sugars were the largest contributors to the HEI-2015 mixture. Nuts/legumes, SSBs/fruit juice, sodium, and DHA/EPA were the largest contributors to the AHEI-2010 mixture. Associations were less precise but consistent in women with spontaneous labors. CONCLUSIONS: Compared to traditional methods, associations of diet index mixtures with gestational length were more robust and identified unique contributors. Additional studies could consider interrogating these statistical approaches using other dietary indices and health outcomes.

Relationship between plasma concentration of 17-hydroxyprogesterone caproate and gestational age at preterm delivery.

BACKGROUND: The effectiveness of 17-hydroxyprogesterone caproate is unclear as trials have provided conflicting results. With the absence of fundamental pharmacologic studies addressing dosing or the relationship between drug concentration and gestational age at delivery, the effectiveness of the medication cannot be evaluated. OBJECTIVE: This study aimed to evaluate the relationship between plasma concentrations of 17-hydroxyprogesterone caproate and preterm birth rates and gestational age at preterm delivery and to assess the safety of the 500-mg dose. STUDY DESIGN: This study recruited 2 cohorts with previous spontaneous preterm birth; 1 cohort (n=143) was randomly assigned to either 250-mg or 500-mg 17-hydroxyprogesterone caproate, and the other cohort (n=16) was receiving the 250-mg dose for routine care. Steady-state trough plasma concentrations of 17-hydroxyprogesterone caproate obtained at 26 to 30 weeks of gestation were correlated to dose, spontaneous preterm birth rates, and measures of gestational length. Furthermore, maternal and neonatal safety outcomes were evaluated according to dose. RESULTS: There was a dose proportional increase in trough plasma concentrations with the 250-mg (median, 8.6 ng/m; n=66) and 500-mg (median, 16.2 ng/mL; n=55) doses. In 116 compliant participants with blood samples, drug concentration was not related to the spontaneous preterm birth rate (odds ratio, 1.00; 95% confidence interval, 0.93-1.08). However, there was a significant relationship between drug concentration and both the interval from the first administration to delivery (interval A: coefficient, 1.11; 95% confidence interval, 0.00-2.23; P=.05) and the interval from the 26- to 30-week blood draw to delivery (interval B: coefficient, 1.56; 95% confidence interval, 0.25-2.87; P=.02). The spontaneous preterm birth rate or measures of gestational length were not related to dose. Postenrollment cerclage adversely affected all pharmacodynamic assessments because it was a powerful predictor of spontaneous preterm birth (odds ratio, 4.03; 95% confidence interval, 1.24-13.19; P=.021) and both measures of gestational length (interval A [coefficient, -14.9; 95% confidence interval, -26.3 to -3.4; P=.011] and interval B [coefficient, -15.9; 95% confidence interval, -25.8 to -5.9; P=.002]). Initial cervical length was significantly related to the risk of postenrollment cerclage (odds ratio, 0.80; 95% confidence interval, 0.70-0.92; P=.001). Maternal and neonatal safety outcomes were similar in both dosing groups. CONCLUSION: In this pharmacodynamic study, trough plasma 17-hydroxyprogesterone caproate concentrations were significantly associated with gestational age at preterm birth but not with the preterm birth rate. Postenrollment cerclage was a powerful predictor of spontaneous preterm birth rate and gestational length. Initial cervical length predicted the risk of postenrollment cerclage. Adverse events were similar with the 500-mg and 250-mg doses of 17-hydroxyprogesterone caproate.

Pregnancy-specific anxiety and gestational length: The mediating role of diurnal cortisol indices.

BACKGROUND: Preterm birth or shorter gestation is a common adverse pregnancy outcome. Pregnancy-specific anxiety is robustly associated with risk for shorter gestation. Hypothalamic-pituitary-adrenal (HPA) dysregulation, indicated by diurnal cortisol index variability [slope, area-under-the-curve (AUC) or cortisol awakening response (CAR)], could mediate associations between pregnancy-specific anxiety and shorter gestation. The purpose of this study was to explore whether diurnal cortisol index variability mediates associations between pregnancy-specific anxiety and gestational length. METHODS: A sample of 149 women from the Healthy Babies Before Birth study reported pregnancy-specific anxiety in early pregnancy. Saliva samples were taken at three times during pregnancy, for two days each, at wake, 30 min post wake, noon, and evening. Diurnal cortisol indices were calculated using standard approaches. Pregnancy cortisol index variability was calculated across pregnancy timepoints. Gestational length was derived from medical charts. Covariates were sociodemographics, parity and obstetric risk. Mediation models were tested using SPSS PROCESS. RESULTS: There was a significant indirect effect of pregnancy-specific anxiety on gestational length via CAR variability, b(SE)= -0.102(0.057), .95CI [- 0.227,- 0.008]. Higher pregnancy-specific anxiety was associated with lower CAR variability, b(SE)= -0.019(0.008), p = .022, and lower CAR variability was associated with shorter gestation, b(SE)= 5.29(2.64), p = .047. Neither AUC or slope variability mediated associations between pregnancy-specific anxiety and gestational length. CONCLUSION: Lower CAR variability during pregnancy mediated the association between higher pregnancy-specific anxiety and shorter gestational length. Pregnancy-specific anxiety could dysregulate HPA axis activity, as indicated by lower CAR variability, demonstrating the importance of the HPA axis system in regulating pregnancy outcomes.

Obstetric risk in pregnancy interacts with hair cortisone levels to reduce gestational length.

Background: Maternal psychological stress has been linked to preterm birth. However, the differential contribution of psychological stress versus stress hormones is not clear. Studies focus primarily on perceived stress and cortisol, with few assessing its inter-convertible hormone cortisone. Furthermore, little is known about the potential moderating roles of obstetric risk and fetal sex in the relationship between maternal stress and gestational length. This gap in knowledge is particularly evident for rural women who typically experience chronic multiple stressors during pregnancy. We explored the relationship of hormonal and psychological stress to gestational length and the effects of obstetric risks and fetal sex on this relationship among Kenyan pregnant women. Methods: The sample included 130 women recruited between 22 to 28 weeks gestation. They completed a clinical and sociodemographic questionnaire together with the Perceived Stress Scale and provided a hair sample for cortisol and cortisone assay. Women underwent an ultrasound to assess weeks of gestation. At delivery, their pregnancy-related health problems were identified using information extracted from medical records to compile each woman's number of pregnancy risks on the Obstetric Medical Risk Index (OMRI). Results: Perceived stress and hair cortisol were not significant predictors of gestational length. However, a greater number of obstetric risks on the OMRI was associated with shorter gestational length. This effect was further explained by the interaction between obstetric risk and hair cortisone (B = 0.709, p = 0.02). Hair cortisone levels of mothers who had a shorter gestation were significantly higher in mothers with 2 or more risks on the OMRI but not among mothers with only one or no risks (t = 2.39, p = 0.02). Fetal sex had no relationship to gestational length and also had no moderating effect on the relationship between any stress-related metric and gestational length. Conclusion: Cortisone levels may increase in anticipation of shorter gestation as a compensatory response to increased obstetric risk. Elevated cortisone may be a more sensitive marker of risk for early delivery than cortisol or psychological stress, with salience for both the male and female fetus.

Maternal diet quality moderates associations between parabens and birth outcomes.

BACKGROUND/OBJECTIVE: Maternal paraben exposure and diet quality are both independently associated with birth outcomes, but whether these interact is unknown. We assessed sex-specific associations of parabens with birth outcomes and differences by maternal diet quality. METHODS: Illinois pregnant women (n = 458) provided five first-morning urines collected at 8-40 weeks gestation, which we pooled for quantification of ethylparaben, methylparaben, and propylparaben concentrations. We collected/measured gestational age at delivery, birth weight, body length, and head circumference within 24 h of birth, and calculated sex-specific birth weight-for-gestational-age z-scores and weight/length ratio. Women completed three-month food frequency questionnaires in early and mid-to-late pregnancy, which we used to calculate the Alternative Healthy Eating Index (AHEI)-2010. Linear regression models evaluated sex-specific associations of parabens with birth outcomes, and differences in associations by average pregnancy AHEI-2010. RESULTS: In this predominately non-Hispanic white, college-educated sample, maternal urinary paraben concentrations were only modestly inversely associated with head circumference and gestational length. However, methylparaben and propylparaben were inversely associated with birth weight, birth weight z-scores, body length, and weight/length ratio in female, but not male newborns. For example, each 2-fold increase in methylparaben concentrations was associated with -46.61 g (95% CI: -74.70, -18.51) lower birth weight, -0.09 (95% CI: -0.15, -0.03) lower birth weight z-scores, -0.21 cm (95% CI: -0.34, -0.07) shorter body length, and -0.64 g/cm (95% CI: -1.10, -0.19) smaller weight/length ratio in females. These inverse associations were more prominent in females of mothers with poorer diets (AHEI-2010 < median), but attenuated in those with healthier diets (AHEI-2010 ≥ median). In newborn males of mothers with healthier diets, moderate inverse associations emerged for propylparaben with gestational length and head circumference. CONCLUSIONS: Maternal diet may moderate associations of parabens with birth size in a sex-specific manner. Additional studies may consider understanding the inflammatory and metabolic mechanisms underlying these findings.

Telomeres, oxidative stress, and timing for spontaneous term and preterm labor.

Telomeres are nucleoprotein complexes located at the distal ends of chromosomes. In adults, progressive telomere shortening occurs throughout the lifetime and is thought to contribute to progressive aging, physiological senescence, multiorgan dysfunction, and ultimately, death. As discussed in this review, multiple lines of evidence provide support for the biological plausibility that a telomere-based clock mechanism also determines the length of gestation, leading to the onset of labor (parturition). After telomere expansion at the beginning of pregnancy, the telomere lengths in the gestational tissues (ie, the placenta and fetal membranes) progressively shorten throughout the remainder of pregnancy. The rate of telomere shortening can be accelerated by conditions that affect the mother and result in oxidative stress. Preterm births in the United States are associated with multiple risk factors that are linked with increased oxidative stress. Antioxidant vitamins (ie, vitamins E and C) mitigate the effects of oxidative stress and delay or prevent telomere shortening. Clinical trials with vitamins E and C and with multivitamins started during the periconception period have been associated with reduced rates of preterm births. In the United States, African-American women have a 2-3-fold higher rate of preterm birth. African-American women have multiple risk factors for premature birth, all of which are distinct and potentially additive with regard to epigenetic telomere shortening. The "weathering effect" is the hypothesis to explain the increased rates of chronic illness, disabilities, and early death observed in African-Americans. With regard to pregnancy, accelerated weathering with the associated telomere shortening in the gestational tissues would not only explain the preterm birth disparity but could also explain why highly educated, affluent African-American women continue to have an increased rate of preterm birth. These studies suggest that the racial disparities in preterm birth are potentially mediated by telomere shortening produced by lifetime or even generational exposure to the effects of systemic racism and socioeconomic marginalization. In conclusion, this review presents multiple lines of evidence supporting a novel hypothesis regarding the biological clock mechanism that determines the length of pregnancy, and it opens the possibility of new approaches to prevent or reduce the rate of spontaneous preterm birth.

Associations of COVID-19 lockdown with gestational length and preterm birth in China.

BACKGROUND: The effects of COVID-19 lockdown measures on maternal and fetal health remain unclear. We examined the associations of COVID-19 lockdown with gestational length and preterm birth (PTB) in a Chinese population. METHODS: We obtained medical records of 595,396 singleton live infants born between 2015 and 2020 in 5 cities in Guangdong Province, South China. The exposed group (N = 101,900) included women who experienced the COVID-19 Level I lockdown (1/23-2/24/2020) during pregnancy, while the unexposed group (N = 493,496) included women who were pregnant during the same calendar months in 2015-2019. Cumulative exposure was calculated based on days exposed to different levels of emergency responses with different weighting. Generalized linear regression models were applied to estimate the associations of lockdown exposure with gestational length and risk of PTB (< 37 weeks). RESULTS: The exposed group had a shorter mean gestational length than the unexposed group (38.66 vs 38.74 weeks: adjusted ß = - 0.06 week [95%CI, - 0.07, - 0.05 week]). The exposed group also had a higher risk of PTB (5.7% vs 5.3%; adjusted OR = 1.08 [95%CI, 1.05, 1.11]). These associations seemed to be stronger when exposure occurred before or during the 23rd gestational week (GW) than during or after the 24th GW. Similarly, higher cumulative lockdown exposure was associated with a shorter gestational length and a higher risk of PTB. CONCLUSIONS: The COVID-19 lockdown measures were associated with a slightly shorter gestational length and a moderately higher risk of PTB. Early and middle pregnancy periods may be a more susceptible exposure window.

Maternal Stress Before Conception Is Associated with Shorter Gestation.

BACKGROUND: Stress in pregnancy predicts adverse birth outcomes. Stressors occurring prior to conception may also pose risk for the mother and child. The few published studies on preconception stress test a single stress measure and examine only linear associations with birth outcomes. PURPOSE: Guided by findings in the prenatal stress literature, the current study aimed to (i) identify latent factors from a set of preconception stress measures and (ii) examine linear and curvilinear associations between these stress factors and length of gestation. METHODS: Study 1 utilized a sample of 2,637 racially/ethnically diverse women to develop a measurement model of maternal stress from assessments of seven acute and chronic stress measures. Factor analysis revealed three latent factors representing stressors (life events, financial strain, interpersonal violence, discrimination), stress appraisals (perceived stress, parenting stress), and chronic relationship stress (family, partner stress). Study 2 examined the associations of these three latent preconception stress factors with the length of gestation of a subsequent pregnancy in the subset of 360 women who became pregnant within 4.5 years. RESULTS: Controlling for prenatal medical risks, there was a significant linear effect of stress appraisals on the length of gestation such that more perceived stress was associated with shorter gestation. There was a curvilinear effect of stressors on the length of gestation with moderate levels associated with longer gestation. CONCLUSIONS: These results have implications for research on intergenerational origins of developmental adversities and may guide preconception prevention efforts. Findings also inform approaches to the study of stress as a multidimensional construct.

Epigenetic age and pregnancy outcomes: GrimAge acceleration is associated with shorter gestational length and lower birthweight.

BACKGROUND: Advanced biological aging, as measured by epigenetic aging indices, is associated with early mortality and morbidity. Associations between maternal epigenetic aging indices in pregnancy and pregnancy outcomes, namely gestational length and birthweight, have not been assessed. The purpose of this study was to examine whether epigenetic age during pregnancy was associated with gestational length and birthweight. RESULTS: The sample consisted of 77 women from the Los Angeles, CA, area enrolled in the Healthy Babies Before Birth study. Whole blood samples for DNA methylation assay were obtained during the second trimester (15.6 ± 2.15 weeks gestation). Epigenetic age indices GrimAge acceleration (GrimAgeAccel), DNAm PAI-1, DNAm ADM, and DNAm cystatin C were calculated. Gestational length and birthweight were obtained from medical chart review. Covariates were maternal sociodemographic variables, gestational age at blood sample collection, and pre-pregnancy body mass index. In separate covariate-adjusted linear regression models, higher early second trimester GrimAgeAccel, b(SE) = - .171 (.056), p = .004; DNAm PAI-1, b(SE) = - 1.95 × 10-4 (8.5 × 10-5), p = .004; DNAm ADM, b(SE) = - .033 (.011), p = .003; and DNAm cystatin C, b(SE) = 2.10 × 10-5 (8.0 × 10-5), p = .012, were each associated with shorter gestational length. Higher GrimAgeAccel, b(SE) = - 75.2 (19.7), p < .001; DNAm PAI-1, b(SE) = - .079(.031), p = .013; DNAm ADM, b(SE) = - 13.8 (3.87), p = .001; and DNAm cystatin C, b(SE) = - .010 (.003), p = .001, were also associated with lower birthweight, independent of gestational length. DISCUSSION: Higher maternal prenatal GrimAgeAccel, DNAm PAI-1, DNAm ADM, and DNAm cystatin C were associated with shorter gestational length and lower birthweight. These findings suggest that biological age, as measured by these epigenetic indices, could indicate risk for adverse pregnancy outcomes.

"High prepregnancy HbA1c is challenging to improve and affects insulin requirements, gestational length, and birthweight".

BACKGROUND: The aim of this study was to explore how prepregnancy glycosylated hemoglobin (HbA1c) affects the course of HbA1c and insulin requirements during pregnancy, the gestational length, and birthweight. METHODS: An observational cohort study was conducted consisting of 380 women with type 1 diabetes who gave birth 530 times from 2004 to 2014. The participants were divided into four groups according to prepregnancy HbA1c. RESULTS: HbA1c was significantly different between the groups at all time intervals from week 5 to 10 to week 33 to 36 (P ≤ .01). In group 1, with the lowest prepregnancy HbA1c (<6.5% [48 mmol/mol]), HbA1c stayed at the same level throughout pregnancy. In the other groups (group 2: 6.5% [48 mmol/mol]-7.9% [63 mmol/mol], group 3: 8% [64 mmol/mol]-9.9% [86 mmol/mol], and group 4: > 10% [86 mmol/mol]) a decrease in HbA1c was seen in early pregnancy but stabilized from midpregnancy onward. Group 1 had the lowest daily insulin requirements throughout pregnancy among the four groups (P = .001). The relationship between birthweight and prepregnancy HbA1c was found to be inversely U-shaped. Mean gestational length in group 4 was significantly shorter than in group 1 (P = .001). CONCLUSIONS: In this very large cohort, we found that a poor prepregnancy HbA1c is a predictor for poor glycemic control during pregnancy and that HbA1c decreases until midpregnancy and then plateaus. A very poor prepregnancy HbA1c is associated with shorter gestational length and lower birthweight, which is contrary to the common assumption that poor glycemic control leads to higher birthweight.

Maternal dietary selenium intake is associated with increased gestational length and decreased risk of preterm delivery.

The first positive genome-wide association study on gestational length and preterm delivery showed the involvement of an Se metabolism gene. In the present study, we examine the association between maternal intake of Se and Se status with gestational length and preterm delivery in 72 025 women with singleton live births from the population-based, prospective Norwegian Mother, Father and Child Cohort Study (MoBa). A self-reported, semi-quantitative FFQ answered in pregnancy week 22 was used to estimate Se intake during the first half of pregnancy. Associations were analysed with adjusted linear and Cox regressions. Se status was assessed in whole blood collected in gestational week 17 (n 2637). Median dietary Se intake was 53 (interquartile range (IQR) 44-62) µg/d, supplements provided additionally 50 (IQR 30-75) µg/d for supplement users (n 23 409). Maternal dietary Se intake was significantly associated with prolonged gestational length (ß per sd = 0·25, 95 % CI, 0·07, 0·43) and decreased risk of preterm delivery (n 3618, hazard ratio per sd = 0·92, 95 % CI, 0·87, 0·98). Neither Se intake from supplements nor maternal blood Se status was associated with gestational length or preterm delivery. Hence, the present study showed that maternal dietary Se intake but not intake of Se-containing supplements, during the first half of pregnancy was significantly associated with decreased risk of preterm delivery. Further investigations, preferably in the form of a large randomised controlled trial, are needed to elucidate the impact of Se on pregnancy duration.

Pro-inflammatory immune cell gene expression during the third trimester of pregnancy is associated with shorter gestational length and lower birthweight.

PROBLEM: Altered maternal immune function predicts risk for shorter gestation and low birthweight. Few studies examine associations between prenatal immune cell gene expression and gestational length or birthweight. No studies examine which cell types drive associations. The purpose of this study is to explore associations between peripheral blood immune cell gene expression and gestational length and birthweight, using transcript origin analysis. METHOD OF STUDY: Eighty-nine women were drawn from the Community Child Health Network cohort. Third trimester maternal dried blood spots were used for genome-wide transcriptional (mRNA) profiling. Gestational length and birthweight were obtained from medical charts. Covariates were age, race/ethnicity, pre-pregnancy body mass index, smoking, gestational age at blood sampling, and pregnancy infections. Associations between gene expression profiles and gestational length and birthweight were tested using general linear models. The Transcription Element Listening System (TELiS) bioinformatics analysis quantified upstream transcription factor activity. Transcript origin analysis identified leukocyte subsets mediating observed effects. RESULTS: Shorter gestation was predicted by increased NF-kB (TFBM ratio = -0.582 ± 0.172, P < .001) and monocyte activity (diagnosticity score = 0.172 ± 0.054, P < .001). Longer gestation was associated with increased dendritic cell activity (diagnosticity score = 0.194 ± 0.039, P < .001). Increased AP-1 activity predicted lower birthweight (TFBM ratio = -0.240 ± 0.111, P = .031). Dendritic cells and CD4+ and CD8+ T cells predicted birthweight-related gene expression differences (diagnosticity score P's < 0.021). CONCLUSION: Higher third trimester pro-inflammatory gene expression predicted shorter gestation and lower birthweight. Variations in monocyte and dendritic cell biology contributed to both effects, and T-cell biology contributed to higher birthweight. These analyses clarify the role of myeloid/lymphoid lineage immune regulation in pregnancy outcomes.

Socioeconomic Status, Preeclampsia Risk and Gestational Length in Black and White Women.

BACKGROUND: Higher socioeconomic status (SES) has less impact on cardio-metabolic disease and preterm birth risk among Black women compared to White women, an effect called "diminishing returns." No studies have tested whether this also occurs for pregnancy cardio-metabolic disease, specifically preeclampsia, or whether preeclampsia risk could account for race-by-SES disparities in birth timing. METHODS: A sample of 718,604 Black and White women was drawn from a population-based California cohort of singleton births. Education, public health insurance status, gestational length, and preeclampsia diagnosis were extracted from a State-maintained birth cohort database. Age, prenatal care, diabetes diagnosis, smoking during pregnancy, and pre-pregnancy body mass index were covariates. RESULTS: In logistic regression models predicting preeclampsia risk, the race-by-SES interaction (for both education and insurance status) was significant. White women were at lower risk for preeclampsia, and higher SES further reduced risk. Black women were at higher risk for preeclampsia, and SES did not attenuate risk. In pathway analyses predicting gestational length, an indirect effect of the race-by-SES interaction was observed. Among White women, higher SES predicted lower preeclampsia risk, which in turn predicted longer gestation. The same was not observed for Black women. CONCLUSIONS: Compared to White women, Black women had increased preeclampsia risk. Higher SES attenuated risk for preeclampsia among White women, but not for Black women. Similarly, higher SES indirectly predicted longer gestational length via reduced preeclampsia risk among White women, but not for Black women. These findings are consistent with diminishing returns of higher SES for Black women with respect to preeclampsia.

Significance of gestational weight gain in spontaneous onset of labor at term.

AIM: To investigate the significance of gestational weight gain (GWG) in association with the spontaneous onset of labor at term. METHODS: A retrospective cohort study on 985 pregnant women (629 nullipara and 356 pluripara) who delivered singleton babies at term was conducted. We reviewed the maternal demographics (age, parity, prepregnancy body mass index [BMI]) and the perinatal outcomes (gestational age [GA] and the type [spontaneous or induced] of labor onset, and GWG). The subjects were categorized by prepregnancy BMI and GWG. The rates of spontaneous onset of labor were compared between the nullipara and pluripara groups. Kaplan-Meier survival analysis was applied to evaluate the time to spontaneous labor according to prepregnancy BMI and GWG. A Cox proportional hazards model was used to determine the independent predictive factor for spontaneous onset of labor. RESULTS: In both the nullipara and pluripara group, women with prepregnancy obesity were less likely to enter spontaneous labor. In nullipara, women with excessive weight gain were less likely to enter spontaneous labor. In pluripara, women with poor gain were more likely to enter spontaneous labor. In the multivariate model, GWG was independently associated with the spontaneous onset of labor in both nullipara (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.75-0.98, P = 0.03) and pluripara (HR 0.82, 95% CI 0.64-0.93, P = 0.005). CONCLUSION: Greater maternal weight gain was significantly associated with longer gestation and a decreased likelihood of spontaneous onset of labor at term.

Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study.

BACKGROUND: Glyphosate (GLY) is the most heavily used herbicide worldwide but the extent of exposure in human pregnancy remains unknown. Its residues are found in the environment, major crops, and food items that humans, including pregnant women, consume daily. Since GLY exposure in pregnancy may also increase fetal exposure risk, we designed a birth-cohort study to determine exposure frequency, potential exposure pathways, and associations with fetal growth indicators and pregnancy length. METHOD: Urine and residential drinking water samples were obtained from 71 women with singleton pregnancies living in Central Indiana while they received routine prenatal care. GLY measurements were performed using liquid chromatography-tandem mass spectrometry. Demographic and survey information relating to food and water consumption, stress, and residence were obtained by questionnaire. Maternal risk factors and neonatal outcomes were abstracted from medical records. Correlation analyses were used to assess relationships of urine GLY levels with fetal growth indicators and gestational length. RESULTS: The mean age of participants was 29 years, and the majority were Caucasian. Ninety three percent of the pregnant women had GLY levels above the limit of detection (0.1 ng/mL). Mean urinary GLY was 3.40 ng/mL (range 0.5-7.20 ng/mL). Higher GLY levels were found in women who lived in rural areas (p = 0.02), and in those who consumed > 24 oz. of caffeinated beverages per day (p = 0.004). None of the drinking water samples had detectable GLY levels. We observed no correlations with fetal growth indicators such as birth weight percentile and head circumference. However, higher GLY urine levels were significantly correlated with shortened gestational lengths (r = - 0.28, p = 0.02). CONCLUSIONS: This is the first study of GLY exposure in US pregnant women using urine specimens as a direct measure of exposure. We found that > 90% of pregnant women had detectable GLY levels and that these levels correlated significantly with shortened pregnancy lengths. Although our study cohort was small and regional and had limited racial/ethnic diversity, it provides direct evidence of maternal GLY exposure and a significant correlation with shortened pregnancy. Further investigations in a more geographically and racially diverse cohort would be necessary before these findings could be generalized.

Hydroxylated polychlorinated biphenyl metabolites (OH-PCBs), maternal smoking and size at birth.

In a sample of 442 births from the Child Health and Development Studies cohort, we examined associations between maternal prenatal exposure to hydroxylated polychlorinated biphenyl metabolites (OH-PCBs) and pregnancy outcomes, and whether associations were mediated by maternal thyroid hormone levels and/or modified by maternal smoking. Compared to nonsmokers, smokers had twice the mean concentration of 4-OH-CB107 (p<0.001) and lower levels of its parent compound, PCB118 (p=0.001). Among mothers who smoked, the birth weight of newborns with maternal concentrations of 4-OH-CB107 in the upper quartile was 316g lighter (95% confidence interval (CI) 566, 65) compared to those with maternal concentrations in the lowest quartile, after control for PCB118 and other potential confounders. This association was not observed for non-smoking mothers and was not mediated by maternal thyroid hormone levels. Maternal prenatal 4-OH-CB107 levels appear to be influenced by maternal smoking and contribute to lower birth weight among smokers.

Prenatal exposure to perfluoroalkyl substances and anogenital distance at 3 months of age in a Danish mother-child cohort.

In the Odense child cohort, serum concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 638 pregnant women. Birth weight, head and abdominal circumferences and gestational age were determined. Anogenital distance (AGD), the distance from the anus to the genital organs, and penile width were measured 3 months after expected date of birth in 511 children. PFOS, PFHxS, PFNA and PFDA were associated with a decreased AGD in girls (p-trend<0.05) after adjusting for age and weight-for-age standard deviation score. PFOS in the highest quartile was associated with a 2.8mm (95% confidence intervals -4.5; -1.1) reduction in AGD in girls. No such tendencies were seen in boys. However, a tendency toward increased birth weight in girls and reduced birth weight in boys suggests that sex-dimorphic effects may occur from endocrine disrupting effects of these substances.