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Abstract Background Epigenetic modifications, particularly DNA methylation (DNAm) in cord blood, are an important biological marker of how external exposures during gestation can influence the in-utero environment and subsequent offspring development. Despite the recognized importance of DNAm during gestation, comparative studies to determine the consistency of these epigenetic signals across different ethnic groups are largely absent. To address this gap, we first performed epigenome-wide association studies (EWAS) of gestational age (GA) using newborn cord blood DNAm comparatively in a white European (n = 342) and a South Asian (n = 490) birth cohort living in Canada. Then, we capitalized on established cord blood epigenetic GA clocks to examine the associations between maternal exposures, offspring characteristics and epigenetic GA, as well as GA acceleration, defined as the residual difference between epigenetic and chronological GA at birth. Results Individual EWASs confirmed 1,211 and 1,543 differentially methylated CpGs previously reported to be associated with GA, in white European and South Asian cohorts, respectively, with a similar distribution of effects. We confirmed that Bohlin’s cord blood GA clock was robustly correlated with GA in white Europeans (r = 0.71; p = 6.0 × 10–54) and South Asians (r = 0.66; p = 6.9 × 10–64). In both cohorts, Bohlin’s clock was positively associated with newborn weight and length and negatively associated with parity, newborn female sex, and gestational diabetes. Exclusive to South Asians, the GA clock was positively associated with the newborn ponderal index, while pre-pregnancy weight and gestational weight gain were strongly predictive of increased epigenetic GA in white Europeans. Important predictors of GA acceleration included gestational diabetes mellitus, newborn sex, and parity in both cohorts. Conclusions These results demonstrate the consistent DNAm signatures of GA and the utility of Bohlin’s GA clock across the two populations. Although the overall pattern of DNAm is similar, its connections with the mother's environment and the baby's anthropometrics can differ between the two groups. Further research is needed to understand these unique relationships.

While its etiology is not fully elucidated, preterm birth represents a major public health concern as it is the leading cause of child mortality and morbidity. Stress is one of the most common perinatal conditions and may increase the risk of preterm birth. In this paper we aimed to investigate the association of maternal perceived stress and anxiety with length of gestation. We used harmonized data from five birth cohorts from Canada, France, and Norway. A total of 5297 pregnancies of singletons were included in the analysis of perceived stress and gestational duration, and 55,775 pregnancies for anxiety. Federated analyses were performed through the DataSHIELD platform using Cox regression models within intervals of gestational age. The models were fit for each cohort separately, and the cohort-specific results were combined using random effects study-level meta-analysis. Moderate and high levels of perceived stress during pregnancy were associated with a shorter length of gestation in the very/moderately preterm interval [moderate: hazard ratio (HR) 1.92 (95%CI 0.83, 4.48); high: 2.04 (95%CI 0.77, 5.37)], albeit not statistically significant. No association was found for the other intervals. Anxiety was associated with gestational duration in the very/moderately preterm interval [1.66 (95%CI 1.32, 2.08)], and in the early term interval [1.15 (95%CI 1.08, 1.23)]. Our findings suggest that perceived stress and anxiety are associated with an increased risk of earlier birth, but only in the earliest gestational ages. We also found an association in the early term period for anxiety, but the result was only driven by the largest cohort, which collected information the latest in pregnancy. This raised a potential issue of reverse causality as anxiety later in pregnancy could be due to concerns about early signs of a possible preterm birth. [ABSTRACT FROM AUTHOR]

Yanxu Zhong,1,2 Huan Lu,3 Xiaodan Lu,4 Zhini He,4 Yuyan Jiang,1 Jie Chen,1 Tippawan Liabsuetrakul2 1Food Safety Monitoring and Evaluation Department, Guangxi Zhuang Autonomous Region Centre for Disease Control and Prevention, Nanning, Guangxi Region, 530000, People’s Republic of China; 2Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; 3Infectious Diseases Department, the Fourth People’s Hospital of Nanning, Nanning, Guangxi Region, 530000, People’s Republic of China; 4Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of ChinaCorrespondence: Tippawan Liabsuetrakul, Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand, Tel +66 74 451165, Fax +66 74 281166, Email tippawan.l@psu.ac.thBackground: Cooking oil and dietary foods are easily contaminated by aflatoxins (AFs) in Guangxi, China where low birth weight and preterm birth were prevalent. However, there are no data on AF exposure in pregnant women or their impact on newborn birth outcomes. This study aims to measure the levels and correlations of AFs in cooking oil, estimated dietary intake (EDI) of AFs in dietary foods, and serum AFB1 albumin adducts (AFB1-alb) with newborn birthweight and gestational age at birth.Methods: A prospective study was conducted among 126 pregnant women in Guangxi, China. All recruited women were interviewed for demographic data and behavior and obstetric information and then followed up until giving birth. AF measurements were obtained from cooking oil, dietary foods, maternal serum, and cord blood and the correlations of AF levels with newborn birthweight and gestational age at birth were tested using correlation analysis.Results: The median EDI of AFs in cooking oil was 2.61 ng/kg.bw/day and in dietary foods 2.95 ng/kg.bw/day. High positive correlations among EDI of aflatoxin B1 (AFB1) from cooking oil and dietary foods were found (r > 0.7). Low positive correlations of AFB1-alb in maternal serum and cord blood and both EDI of AFB1 in both cooking oil and dietary foods were shown (r ≈0.3). Significant correlations between AF levels in both cooking oil and dietary foods with birth weight were found, but very low negative correlations (r = - 0.244 ~ − 0.285). AFB1 levels in foods, maternal serum and cord blood levels were high in pregnant women with newborn low birth weight and preterm birth.Conclusion: The EDIs of AFB1 from both cooking oil and dietary foods were significantly correlated with AFB1-alb in maternal serum and cord blood. Negative correlations of AFs from cooking oils and foods with newborn birth weight should be paid more attention.Keywords: aflatoxins, EDI, birthweight, gestational age at birth, AFB1 albumin adducts

BackgroundThe aim was to investigate gestational age at birth of women after induction of fetal lung maturation (antenatal corticosteroids = ACS) because of imminent preterm birth (PTB), and to quantify incidence of late PTB (gestational age 35, history of preterm delivery, multifetal gestation, gestational diabetes, hypertension, nicotine abuse).MethodsThe study was designed as a retrospective cohort trial, in which the data of all births taking place in 2016 in the German federal state Rhineland-Palatinate were evaluated. Frequency analyses, subgroup analysis (Chi-square tests and Friedman’s tests), as well as multinomial logistic regressions and linear regressions were used to determine odds ratios (OR).ResultsIn total, N = 1,544 patients were included who had been hospitalized due to an imminent PTB and had received ACS, of whom 52% had a late PTB and 8% a PTB with extreme immaturity. Regarding the gestational age at birth, there were only minor differences between the individual risk factors and diagnoses, only AIS patients showed a significantly lower gestational age (mean: 207 days). A significantly increased risk of PTB with extreme immaturity was found in patients with AIS (OR = 5.57) or placental bleeding (OR = 2.10).ConclusionThere is a need for further research in order to be able to apply therapeutic measures more accurately in relation to risk factors and diagnoses.

Purpose: We aimed to describe the distribution of gestational age at birth (GAB) to inform the estimation of GAB when clinical or obstetric estimates are not available for perinatal pharmacoepidemiology studies. Methods: We estimated GAB (median, mode, mean, and standard deviation) and percentage born at each gestational week in groups based on plurality and other variables for live births in CDC's U.S. birth data. Results: In 2020, 3 617 213 newborns had birth certificates with nonmissing GAB. Among singletons (3 501 693), median and mode GAB were both 39 weeks. Births with lower median GAB were from women with eclampsia (37 weeks) or receiving intensive care (37 weeks); newborns receiving intensive care (37 weeks); newborns with birth weight <2500 g (35 weeks), <1500 g (28 weeks), or <1000 g (25 weeks); and newborns not discharged alive (23 weeks). Among twins (112 633), median GAB was 36 weeks (mode, 37 weeks). Additional noteworthy groups were women with 0–6 prenatal visits (median, 34 weeks) or 7–8 prenatal visits (median, 35 weeks) or aged 15–19 years (median, 35 weeks). Conclusions: Some maternal and infant groups had distinct GAB distributions in the United States. This information can be useful in estimating GAB when individual‐level clinical estimates are not available, such as in database studies of medication use during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Maternal pesticide exposure might be associated with adverse pregnancy outcomes through triggering inflammation and oxidative stress and disrupting endocrine functions. Yet the association between prenatal pesticide exposure and risk of preterm birth remains inconclusive. Objectives: To conduct a systematic review and meta-analysis of human observational studies using the Office of Health Assessment and Translation (OHAT) framework to explore the association of per ten-fold increase of pesticide concentrations in maternal biological samples during pregnancy with risk of preterm birth and length of gestational age at birth. Data source: Five English (PubMed, Embase, Cochrane Library, Web of Science and Scopus) and 3 Chinese databases (China national knowledge infrastructure (CNKI), Wanfang Data, and Chinese Biomedical Literature Database (CBM)) were searched till Jan 18th, 2023. Study eligibility criteria, participants, and interventions: To be included, pesticide exposure should be measured in maternal biological samples during pregnancy and in log-transformed forms. The primary outcome was preterm birth and the secondary outcome was gestational age at birth. Study appraisal, synthesis methods and confidence assessment: Quality of studies was evaluated using OHAT Risk of Bias Tool. Evidence was quantitatively synthesized with Correlated and Hierarchical Effects (CHE) model. The confidence rating in the body of evidence was done using OHAT. Results: A total of 21 studies reported by 18 papers were included, with 7 studies for preterm birth and 19 for gestational age at birth. The meta-analysis found a ten-fold increase of pesticide concentrations was potentially associated with risk of preterm birth (pooled OR = 1.28; 95%CI: 0.93, 1.78) and shortened gestational age at birth (β = −0.10; 95%CI: −0.21, 0.01). Sampling biospecimens in different trimesters was identified as a potential modifier in the association between pesticide exposure and length of gestational age (F = 2.77, P

Background: Preterm birth is one of the most important contributors to neonatal mortality and morbidity. Experiencing stress during pregnancy may increase the risk of adverse birth outcomes, including preterm birth. This association has been observed in previous studies, but differences in measures used limit comparability. Objective: The objective of the study was to investigate the association between two measures of maternal stress during pregnancy, life stress and emotional distress, and gestation duration. Methods: Women recruited in the Danish National Birth Cohort from 1996 to 2002, who provided information on their stress level during pregnancy and expecting a singleton baby, were included in the study. We assessed the associations between the level of life stress and emotional distress in quartiles, both collected at 31 weeks of pregnancy on average, and the rate of giving birth using Cox regression within intervals of the gestational period. Results: A total of 80,991 pregnancies were included. Women reporting moderate or high levels of life stress vs no stress had a higher rate of giving birth earlier within all intervals of gestational age (e.g. high level: 27–33 weeks: hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.04, 1.84; 34–36 weeks: 1.10, 95% CI 0.97, 1.25; 37–38 weeks: 1.21, 95% CI 1.15, 1.28). These associations between life stress and preterm birth were mainly driven by pregnancy worries. For emotional distress, a high level of distress was associated with shorter length of gestation in the preterm (27–33 weeks: 1.38, 95% CI 1.02, 1.86; 34–36 weeks: 1.05, 95% CI 0.91, 1.19) and early term (1.11, 95% CI 1.04, 1.17) intervals. Conclusions: Emotional distress and life stress were shown to be associated with gestational age at birth, with pregnancy‐related stress being the single stressor driving the association. This suggests that reverse causality may, at least in parts, explain the earlier findings of stress as a risk factor for preterm birth. [ABSTRACT FROM AUTHOR]

Health administrative data are oftentimes of limited use in epidemiological study on drug safety in pregnancy, due to lacking information on gestational age at birth (GAB). Although several studies have proposed algorithms to estimate GAB using claims database, failing to incorporate the unique distributional shape of GAB, can introduce bias in estimates and subsequent modeling. Hence, we develop a Bayesian latent class model to predict GAB. The model employs a mixture of Gaussian distributions with linear covariates within each class. This approach allows modeling heterogeneity in the population by identifying latent subgroups and estimating class‐specific regression coefficients. We fit this model in a Bayesian framework conducting posterior computation with Markov Chain Monte Carlo methods. The method is illustrated with a dataset of 10,043 Rhode Island Medicaid mother–child pairs. We found that the three‐class and six‐class mixture specifications maximized prediction accuracy. Based on our results, Medicaid women were partitioned into three classes, featured by extreme preterm or preterm birth, preterm or" early" term birth, and" late" term birth. Obstetrical complications appeared to pose a significant influence on class‐membership. Altogether, compared to traditional linear models our approach shows an advantage in predictive accuracy, because of superior flexibility in modeling a skewed response and population heterogeneity. [ABSTRACT FROM AUTHOR]

Objectives: Intergenerational transmission of trauma occurs when the effects of childhood maltreatment (CM) influence the next generation's development and health; prenatal programming via maternal mood symptoms is a potential pathway. CM is a risk factor for bipolar disorder which is present in 1.8% of pregnant women. Mood symptoms are likely to increase during pregnancy, particularly for those with a history of CM. We examined whether there was evidence for intergenerational transmission of trauma in utero in this population, and whether maternal mood was a transmission pathway. Methods: CM and maternal mood were self‐reported by N = 82 pregnant women in treatment for bipolar disorder. Fetal heart rate variability (FHRV) was measured at 24, 30, and 36 weeks' gestation. Gestational age at birth and birth weight were obtained from medical charts. Results: A cluster analysis yielded two groups, Symptom+ (18.29%) and Euthymic (81.71%), who differed on severe mood symptoms (p < 0.001) but not on medication use. The Symptom+ group had more CM exposures (p < 0.001), a trend of lower FHRV (p = 0.077), and greater birth complications (33.3% vs. 6.07% born preterm p < 0.01). Maternal prenatal mood mediated the association between maternal CM and birth weight in both sexes and at trend level for gestational age at birth in females. Conclusions: This is the first study to identify intergenerational effects of maternal CM prior to postnatal influences in a sample of pregnant women with bipolar disorder. These findings underscore the potential enduring impact of CM for women with severe psychiatric illness and their children. [ABSTRACT FROM AUTHOR]

DNA methylation is highly sensitive to in utero perturbations and has an established role in both embryonic development and regulation of gene expression. The foetal genetic component has been previously shown to contribute significantly to the timing of birth, yet little is known about the identity and behaviour of individual genes. The aim of this study was to test the extent genome-wide DNA methylation levels in umbilical cord blood were associated with gestational age at birth (GA). Findings were validated in an independent sample and evidence for the regulation of gene expression was evaluated for cis gene relationships in specimens with multi-omic data. Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450 K BeadChip, was associated with GA for 2,372 CpG probes (5% FDR) in both the Pregnancy, Race, Environment, Genes (PREG) and Newborn Epigenetic Study (NEST) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. Gene pathways identified are consistent with the hypothesis of pathogen detection and response by the immune system to elicit premature labour as a consequence of unscheduled inflammation.

Objective: To investigate the accuracy of fetal weight estimation made by the last prenatal ultrasound measurement in low birth weight newborns (

OBJECTIVE: To investigate the accuracy of fetal weight estimation made by the last prenatal ultrasound measurement in low birth weight newborns (<2500 g). STUDY DESIGN: A total of 1082 women were evaluated in this retrospective cohort study. Demographic and clinical information of the mother and newborn and obstetric ultrasonography measurements and findings performed in the last week before birth were recorded. Accuracy of fetal weight estimation and parameters affecting it was investigated. RESULTS: Accurate estimation rates were lower in the term compared to the preterm delivery group; and in the SGA group compared to the AGA group (respectively, p=0.016, p=0.032). Accurate estimation rates (p=0.182) were comparable between the 500-1500 g and 1501-2500 g subgroups. The multiple linear regression analysis showed that gestational age at birth, birth weight, examination during labor, and duration between examination to delivery were statistically significant for the accurate estimation(p=0.001). CONCLUSIONS: Accurate estimation rates were lower in the term compared to the preterm delivery group, and in the SGA group compared to the AGA group. The factors affecting accurate estimation were found to be gestational age at birth, birth weight, examination during labor, and duration between examination to delivery. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate the association between the early pregnancy vaginal microbiome and spontaneous preterm birth (sPTB) and early term birth (sETB) among African American women.MethodsVaginal samples collected in early pregnancy (8-14 weeks’ gestation) from 436 women enrolled in the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Study underwent 16S rRNA gene sequencing of the V3-V4 region, taxonomic classification, and community state type (CST) assignment. We compared vaginal CST and abundance of taxa for women whose pregnancy ended in sPTB (N = 44) or sETB (N= 84) to those who delivered full term (N = 231).ResultsNearly half of the women had a vaginal microbiome classified as CST IV (Diverse CST), while one-third had CST III (L. iners dominated) and just 16% had CST I, II, or V (non-iners Lactobacillus dominated). Compared to vaginal CST I, II, or V (non-iners Lactobacillus dominated), both CST III (L. iners dominated) and CST IV (Diverse) were associated with sPTB with an adjusted odds ratio (95% confidence interval) of 4.1 (1.1, infinity) and 7.7 (2.2, infinity), respectively, in multivariate logistic regression. In contrast, no vaginal CST was associated with sETB. The linear decomposition model (LDM) based on amplicon sequence variant (ASV) relative abundance found a significant overall effect of the vaginal microbiome on sPTB (p=0.034) but not sETB (p=0.320), whereas the LDM based on presence/absence of ASV found no overall effect on sPTB (p=0.328) but a significant effect on sETB (p=0.030). In testing for ASV-specific effects, the LDM found that no ASV was significantly associated with sPTB considering either relative abundance or presence/absence data after controlling for multiple comparisons (FDR 10%), although in marginal analysis the relative abundance of Gardnerella vaginalis (p=0.011), non-iners Lactobacillus (p=0.016), and Mobiluncus curtisii (p=0.035) and the presence of Atopobium vaginae (p=0.049), BVAB2 (p=0.024), Dialister microaerophilis (p=0.011), and Prevotella amnii (p=0.044) were associated with sPTB. The LDM identified the higher abundance of 7 ASVs and the presence of 13 ASVs, all commonly residents of the gut, as associated with sETB at FDR < 10%.ConclusionsIn this cohort of African American women, an early pregnancy vaginal CST III or IV was associated with an increased risk of sPTB but not sETB. The relative abundance and presence of distinct taxa within the early pregnancy vaginal microbiome was associated with either sPTB or sETB.

Objective: To evaluate the association between the early pregnancy vaginal microbiome and spontaneous preterm birth (sPTB) and early term birth (sETB) among African American women. Methods: Vaginal samples collected in early pregnancy (8-14 weeks' gestation) from 436 women enrolled in the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Study underwent 16S rRNA gene sequencing of the V3-V4 region, taxonomic classification, and community state type (CST) assignment. We compared vaginal CST and abundance of taxa for women whose pregnancy ended in sPTB (N = 44) or sETB (N= 84) to those who delivered full term (N = 231). Results: Nearly half of the women had a vaginal microbiome classified as CST IV (Diverse CST), while one-third had CST III (L. iners dominated) and just 16% had CST I, II, or V (non-iners Lactobacillus dominated). Compared to vaginal CST I, II, or V (non-iners Lactobacillus dominated), both CST III (L. iners dominated) and CST IV (Diverse) were associated with sPTB with an adjusted odds ratio (95% confidence interval) of 4.1 (1.1, infinity) and 7.7 (2.2, infinity), respectively, in multivariate logistic regression. In contrast, no vaginal CST was associated with sETB. The linear decomposition model (LDM) based on amplicon sequence variant (ASV) relative abundance found a significant overall effect of the vaginal microbiome on sPTB (p=0.034) but not sETB (p=0.320), whereas the LDM based on presence/absence of ASV found no overall effect on sPTB (p=0.328) but a significant effect on sETB (p=0.030). In testing for ASV-specific effects, the LDM found that no ASV was significantly associated with sPTB considering either relative abundance or presence/absence data after controlling for multiple comparisons (FDR 10%), although in marginal analysis the relative abundance of Gardnerella vaginalis (p=0.011), non-iners Lactobacillus (p=0.016), and Mobiluncus curtisii (p=0.035) and the presence of Atopobium vaginae (p=0.049), BVAB2 (p=0.024), Dialister microaerophilis (p=0.011), and Prevotella amnii (p=0.044) were associated with sPTB. The LDM identified the higher abundance of 7 ASVs and the presence of 13 ASVs, all commonly residents of the gut, as associated with sETB at FDR < 10%. Conclusions: In this cohort of African American women, an early pregnancy vaginal CST III or IV was associated with an increased risk of sPTB but not sETB. The relative abundance and presence of distinct taxa within the early pregnancy vaginal microbiome was associated with either sPTB or sETB. [ABSTRACT FROM AUTHOR]

Abstract Background Epidemiological evidence suggests that arsenic (As) exposure during pregnancy may reduce infant birth weight. One significant source of As exposure is diet; thus, As may indirectly affect infant growth by mediating the effect of maternal diet on birth weight (BW). This study evaluated the potential mediating effect of As in the relationship between maternal diet and BW, gestational age (GA), and gestational weight gain (GWG). Method The study used a prospective birth cohort in Bangladesh that captured the dietary habits of 1057 pregnant women through validated semi-quantitative food frequency questionnaires. We applied a causal mediation model with counterfactual approach and performed analyses with and without adjustment for total energy intake. Other potential confounders captured by self-report questionnaire were exposure to secondhand tobacco smoke, betel nut chewing, maternal age, education level, household income level, physical activity level during pregnancy, and daily hours spent cooking over open fire. Result No association was found between maternal toenail As and BW. Higher absolute and energy-adjusted protein, fat and fiber intakes were associated with higher toenail As and lower GA and GWG, while higher absolute and energy-adjusted carbohydrate intake was associated with lower toenail As and greater GA and GWG. Mediation analysis showed significant natural indirect effects by toenail As in the relationships between absolute fat, carbohydrate and fiber intake with GA. Specifically, 3% (95% CI: 1–6%) of the association between carbohydrate intake and GA was mediated by change in toenail As, 6% (95% CI: 1–9%) for absolute fat intake and 10% (95% CI: 4–13%) for absolute fiber intake. After adjusting for total energy, no significant mediating effect was observed, suggesting the mediating effect might be due to measurement error or that absolute amount of As exposure rather than the amount in relationship to total energy intake was a more important factor to consider when understanding the negative implication of As on fetal growth. Conclusion The mediating effect of As in the relationship between maternal diet and birth outcome was small and might be due to measurement error.

Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

DNA methylation is highly sensitive to in utero perturbations and has an established role in both embryonic development and regulation of gene expression. The foetal genetic component has been previously shown to contribute significantly to the timing of birth, yet little is known about the identity and behaviour of individual genes. The aim of this study was to test the extent genome-wide DNA methylation levels in umbilical cord blood were associated with gestational age at birth (GA). Findings were validated in an independent sample and evidence for the regulation of gene expression was evaluated for cis gene relationships in specimens with multi-omic data. Genome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450 K BeadChip, was associated with GA for 2,372 CpG probes (5% FDR) in both the Pregnancy, Race, Environment, Genes (PREG) and Newborn Epigenetic Study (NEST) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. Gene pathways identified are consistent with the hypothesis of pathogen detection and response by the immune system to elicit premature labour as a consequence of unscheduled inflammation. [ABSTRACT FROM AUTHOR]

Copyright of Acta Medica Croatica is the property of Croatian Academy of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Maternal periodontitis has been suggested as an important risk factor for preterm low birth weight. The aim of the present observational study was to assess whether full-mouth therapy of periodontitis in pregnant women reduces the risk of preterm low birth weight. Method and Materials: From April 2006 to April 2007, 302 pregnant women who were at less than 22 weeks of gestation were invited to attend a periodontal examination. Consent for periodontal screening was given by 62 mothers; 54 of them met criteria. Consent for periodontal treatment was provided by 12 patients (group 1), whereas 14 patients declined therapy (group 2). No periodontal therapy was indicated in 28 patients (group 3). Nonsurgical treatment was performed in group 1 as full-mouth disinfection between 22 and 30 weeks of gestation. Periodontal reevaluation was performed 4 to 6 weeks later. As primary outcome, the gestational age at the end of pregnancy was assessed in all groups. Secondary outcomes were birth weight and growth restriction. Results: Periodontitis treatment improved periodontal measures (P ≤ .001) in this rather small collective. However, there were no statistically significant differences between treatment group 1 and group 2 in the gestational age, birth weight, or growth restrictions. There were also no statistically significant differences compared to group 3. Conclusions: In consideration to the limited number of patients, full-mouth therapy in pregnant women can improve periodontitis but does not significantly alter the gestational age at birth or birth weight. Therefore, new studies are needed in this field especially with respect to the genetic disposition of mothers to chronic or aggressive periodontal inflammation response. [ABSTRACT FROM AUTHOR]

ObjectiveThe aim was to test a model of the influence of maternal prenatal psychosocial stress on birth outcomes after controlling for biomedical risk.Study designIn a prospective study a sociodemographically homogeneous sample of 90 women was assessed during the third trimester with standard, reliable questionnaires that measured episodic and chronic stress, strain (response to stress), and pregnancy-related anxiety. Birth outcomes included infant birth weight, gestational age at birth, and intrapartum complications. Parity and biomedical (antepartum) risk was also coded. Bivariate and multivariate analyses were performed after controlling for the effects of biomedical risk factors.ResultsIndependent of biomedical risk, each unit increase of prenatal life event stress (from a possible sample range of 14.7 units) was associated with a 55.03 gm decrease in infant birth weight and with a significant increase in the likelihood of low birth weight (odds ratio 1.32), and each unit increase of prenatal pregnancy anxiety (from a possible sample range of 5 units) was associated with a 3-day decrease in gestational age at birth.ConclusionIndependent of biomedical risk, maternal prenatal stress factors are significantly associated with infant birth weight and with gestational age at birth.

Background: Epidemiological evidence suggests that arsenic (As) exposure during pregnancy may reduce infant birth weight. One significant source of As exposure is diet; thus, As may indirectly affect infant growth by mediating the effect of maternal diet on birth weight (BW). This study evaluated the potential mediating effect of As in the relationship between maternal diet and BW, gestational age (GA), and gestational weight gain (GWG).Method: The study used a prospective birth cohort in Bangladesh that captured the dietary habits of 1057 pregnant women through validated semi-quantitative food frequency questionnaires. We applied a causal mediation model with counterfactual approach and performed analyses with and without adjustment for total energy intake. Other potential confounders captured by self-report questionnaire were exposure to secondhand tobacco smoke, betel nut chewing, maternal age, education level, household income level, physical activity level during pregnancy, and daily hours spent cooking over open fire.Result: No association was found between maternal toenail As and BW. Higher absolute and energy-adjusted protein, fat and fiber intakes were associated with higher toenail As and lower GA and GWG, while higher absolute and energy-adjusted carbohydrate intake was associated with lower toenail As and greater GA and GWG. Mediation analysis showed significant natural indirect effects by toenail As in the relationships between absolute fat, carbohydrate and fiber intake with GA. Specifically, 3% (95% CI: 1-6%) of the association between carbohydrate intake and GA was mediated by change in toenail As, 6% (95% CI: 1-9%) for absolute fat intake and 10% (95% CI: 4-13%) for absolute fiber intake. After adjusting for total energy, no significant mediating effect was observed, suggesting the mediating effect might be due to measurement error or that absolute amount of As exposure rather than the amount in relationship to total energy intake was a more important factor to consider when understanding the negative implication of As on fetal growth.Conclusion: The mediating effect of As in the relationship between maternal diet and birth outcome was small and might be due to measurement error. [ABSTRACT FROM AUTHOR]

Background Our aim was to determine whether the postnatal age or postmenstrual age is a more appropriate criterion for evaluating foetal haemoglobin concentrations. Methods Blood samples ( n = 1095) were obtained from 394 infants and were divided into two groups based on gestational age at birth: <37 weeks ( n = 491) and ≥37 weeks ( n = 604). (1) Foetal haemoglobin concentrations divided by one month at age after birth were compared between the groups. (2) Foetal haemoglobin concentrations divided into ≤9 months from last menstruation and one month thereafter were compared between the groups. Results In samples from infants ≥37 weeks' gestational age at birth, the median foetal haemoglobin concentrations were 69.5%, 21.4% and 3.6% at 0-1 month, 2-3 months and ≥5 months after birth, respectively. The median foetal haemoglobin concentrations in infants <37 weeks' gestational age at birth were 75.5%, 62.7% and 5.1% at 0-1 month, 2-3 months and ≥5 months after birth, respectively. The median foetal haemoglobin concentrations in infants <37 weeks' gestational age at birth were significantly higher than that in infants ≥37 weeks' gestational age at birth at all postnatal age points. (2) There was no significant difference between the groups at all age points after nine months of postmenstrual age: 72.5 and 75.3% at 9-10 months, 25.1 and 26.6% at 11-12 months and 5.5 and 4.6% at >13 months after last menstruation in infants ≥37 and <37 weeks' gestational age at birth, respectively. Conclusions Evaluation of foetal haemoglobin concentrations at postmenstrual age is unaffected by gestational age at birth. [ABSTRACT FROM AUTHOR]

Preterm birth adversely affects postnatal brain development. In order to investigate the critical gestational age at birth (GAB) that alters the developmental trajectory of gray and white matter structures in the brain, we investigated diffusion tensor and quantitative T2 mapping data in 43 term-born and 43 preterm-born infants. A novel multivariate linear model-the change point model, was applied to detect change points in fractional anisotropy, mean diffusivity, and T2 relaxation time. Change points captured the "critical" GAB value associated with a change in the linear relation between GAB and MRI measures. The analysis was performed in 126 regions across the whole brain using an atlas-based image quantification approach to investigate the spatial pattern of the critical GAB. Our results demonstrate that the critical GABs are region- and modality-specific, generally following a central-to-peripheral and bottom-to-top order of structural development. This study may offer unique insights into the postnatal neurological development associated with differential degrees of preterm birth. [ABSTRACT FROM AUTHOR]

Background The relationship between gestational age at birth (GA) and alcohol use measures in early adulthood was examined in a large U.K. community-based birth cohort (Avon Longitudinal Study of Parents and Children). Methods A series of linear and logistic regression models were used to test for main effects of a continuous measure of GA on a range of alcohol use measures, and moderation of these associations by sex. In addition, mediation analyses assessed the extent to which significant associations between GA and alcohol use operated indirectly, through influences of the parental environment and/or childhood measures of emotional and behavioral health (EBH). Results Earlier GA significantly predicted never drinking by age 18, but was not associated with other measures of alcohol use behavior among young adult drinkers (i.e., Self-Rating of the Effects of Alcohol, Alcohol Use Disorders Identification Test, or DSM- IV- TR Criteria for Alcohol Dependence). The association between earlier GA and never drinking by age 18 was moderated by sex, such that females born early were less likely to have ever had a drink by age 18. In the full sample, childhood measures of EBH were found to mediate the association between earlier GA and never drinking by age 18. This association was not mediated by parenting factors. Conclusions Earlier GA is associated with never drinking alcohol in early adulthood, in females. Emotional and behavioral difficulties experienced in early childhood may mediate the relationship between earlier GA and never drinking by age 18. [ABSTRACT FROM AUTHOR]

Background While it is well established that very preterm birth (gestational age at birth < 32 weeks) is related to increased attention problems, there is still considerable uncertainty of the effects of moderate or late preterm birth or smallness for gestational age (SGA) on attention regulation. Aims To investigate the impact of gestational age at birth and SGA, birth on child attention problems. Study design Prospective longitudinal cohort study. Subjects A total of 1435 children sampled from the Bavarian Longitudinal Study (BLS). Outcome measures Main outcome variables were parent-reported attention problems and examiner-reported attention skills at 6 and 8 years. Predictors were linked to attention outcomes using hierarchical regression analyses. Results Gestational age at birth ranged from 25 weeks to 41 weeks. We found a quadratic effect of gestational age on attention problems ( β 6 years = 0.161, 95% CI = 0.085; 0.236; β 8 years = 0.211, 95% CI = 0.135; 0.287), and attention skills at 6 and 8 years ( β 6 years = − 0.178, 95% CI = − 0.252; − 0.104; β 8 years = − 0.169, 95% CI = − 0.243; − 0.094). Elective caesarean birth did not predict child attention. In adjusted models, SGA was an additional risk factor for attention problems ( β = 0.080, 95% CI = 0.026; 0.134), and attention skills ( β = − 0.091, 95% CI = − 0.143; − 0.039) at 6 years but not at 8 years after adjusting for child sex and family SES. Conclusion Adverse effects on attention are disproportionately higher at early gestations. In contrast, the impact of SGA status was found to be similar at all gestational ages but disappeared by 8 years. [ABSTRACT FROM AUTHOR]

This review describes how improvements in biometric-genetic studies of twin kinships, half-sibships, and cousinships have now demonstrated a sizeable fetal genetic and maternal genetic contribution to the spontaneous onset of labor. This is an important development because previous literature for the most part reports only an influence of the maternal genome. Current estimates of the percent of variation that is attributable to fetal genetic factors range from 11–35%; the range for the maternal genetic contribution is 13–20%. These same studies demonstrate an even larger influence of environmental sources over and above the influence of genetic sources and previously identified environmental risk factors. With these estimates in hand, a major goal for research on pregnancy duration is to identify specific allelic variation and environmental risk to account for this estimated genetic and environmental variation. A review of the current literature can serve as a guide for future research efforts. [Copyright &y& Elsevier]

Background: The Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) showed no benefit in the reduction of major neonatal mortality/morbidity or neurodevelopment at 2 and 5 years of age. Using the data from the randomized controlled trial and its follow-up, the aim of this study was to evaluate the association between gestational ages at birth in children exposed to single versus multiple courses of antenatal corticosteroid (ACS) therapy in utero and outcomes at 5 years of age. Method: A total of 1719 children, with the breakdown into groupings of <30, 30-36, and ≥ 37 weeks gestation at birth, contributed to the primary outcome: death or survival with a disability in one of the following domains: neuromotor, neurosensory, and neurobehavioral/emotional disability and were included in this analysis. Results: Gestational age at birth was strongly associated with the primary outcome, p < 0.001. Overall, the interaction between ACS groups and gestational age at birth was not significant, p = 0.064. Specifically, in the 2 preterm categories, there was no difference in the primary outcome between single vs. multiple ACS therapy. However, for infants born ≥37 weeks gestation, there was a statistically significant increase in the risk of the primary outcome in multiple ACS therapy, 48/213 (22.5%) compared to 38/249 (15.3%) in the single ACS therapy; OR = 1.69 [95% CI: 1.04, 2.77]; p = 0.037. Conclusion: Preterm birth (<37 weeks gestation) remained the primary factor contributing to an adverse outcome regardless of the number of courses of ACS therapy. Children born ≥ 37 weeks and exposed to multiple ACS therapy may have an increased risk of neurodevelopmental/neurosensory impairment by 5 years of age. To optimize outcomes for infants/children, efforts in reducing the incidence of preterm birth should remain the primary focus in perinatal research. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Pregnant adolescents have high rates of poor birth outcomes, but the causes are unclear. We present a prospective, longitudinal study of pregnant adolescents assessing associations between maternal psychobiological stress indices and offspring gestational age at birth and birthweight. Method: Healthy nulliparous pregnant adolescents were recruited (n=205) and followed during pregnancy. Ambulatory assessments over 24h of perceived psychological stress (collected every 30min) and salivary cortisol (6 samples) and a summary questionnaire, the Perceived Stress Scale, were collected at three time points (13–16, 24–27, and 34–37 gestational weeks). Corticotropin-releasing hormone, C-reactive protein, and interleukin 6 were assayed from blood taken at the latter 2 sessions. A final sample of 119 participants was selected for analyses. Results: The ambulatory assessment of perceived psychological stress was positively correlated with the Perceived Stress Scale (r =.20, p =.03) but neither was associated with any of the biological assays (all ps>.20). Based on backward selection regression models that included all stress variables and relevant covariates, the ambulatory assessments of perceived psychological stress and cortisol — though not the Perceived Stress Scale — were negatively associated with gestational age at birth (F(4, 107)=3.38, p =.01) while cortisol was negatively related to birthweight (F(5, 107)=14.83, p <.0001). Conclusions: Targeted interventions to reduce psychological and biological indicators of heightened stress during pregnancy may have positive public health benefits for the offspring given the associations of shortened gestation and lower birthweight with risk for poor mental and physical health outcomes. [Copyright &y& Elsevier]

Abstract: There is mounting evidence that stress during pregnancy can have detrimental effects on gestation and birth. Existing studies indicate that prenatal stress may increase levels of circulating inflammatory markers that are associated with prematurity and pregnancy complications, suggesting that stress-related changes in the cytokine milieu may increase the risk of poor pregnancy outcome. Previous studies, however, have not clearly connected stress during pregnancy to changes in inflammatory mediators and, in turn, to clinically-relevant outcomes such as premature delivery. The present study sought to directly connect prenatal stress and changes in inflammatory markers to preterm delivery and gestational age at birth (GAB). A sample of 173 women was recruited during the first trimester of pregnancy and followed through delivery. Overall stress, pregnancy-specific distress, and inflammatory markers were assessed early and later in pregnancy, and the predictive value of these measures for preterm birth and GAB was determined. There were significant differences in pregnancy-specific distress, IL-6, and TNF-α between women who delivered prematurely versus those who delivered at term, and elevated levels of pregnancy-specific distress, IL-6, and TNF-α were predictive of shortened GAB overall. Importantly, in many cases, the effects of overall stress and pregnancy-specific distress on GAB were mediated by levels of circulating inflammatory markers. Collectively, these data provide strong evidence that prenatal stress experiences can affect the timing of parturition via alterations in circulating inflammatory mediators, and underscore the need for ongoing research aimed at further understanding the mechanisms and effects of prenatal stress on maternal and infant health. [Copyright &y& Elsevier]

The present study aimed to explore the effectiveness of the combined use of thyroid-stimulating hormone (TSH) and free thyroxine [(FT4); TSH+FT4] levels and gestational age at birth to predict neonatal hypothyroidism and to identify the risk factors associated with the disease. The clinical data of 686 neonates with suspected hypothyroidism (TSH >10 mIU/l) who were admitted to The First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. From these, 70 neonates with confirmed hypothyroidism were assigned to the patient group and another 70 neonates with normal thyroid function to the normal (control) group. Sex, gestational age at birth, Apgar score, birth weight, body length, head circumference and heart rate data were collected. TSH and FT4 levels were measured by electrochemiluminescence immunoassay, and the predictive value of combined use of TSH+FT4 and gestational age at birth on neonatal hypothyroidism was analyzed. The prespecified secondary outcomes were the risk factors for neonatal hypothyroidism determined using univariate and logistic regression analyses. TSH levels were significantly higher, whereas FT4 levels were lower in the patient group at 3 days of age compared with the control group (P<0.05). After 8-week treatment with thyroxine, these levels were not significantly different between the patient and control groups (P<0.05). The combined use of TSH+FT4 levels and gestational age at birth to predict neonatal hypothyroidism demonstrated a significantly improved sensitivity, specificity, accuracy, positive predictive value and negative predictive value (92.86, 97.26, 96.76, 81.25 and 99.07%, respectively) compared with the use of only TSH+FT4 levels (P<0.05). Logistic regression analysis revealed a low gestational age at birth, maternal thyroid dysfunction and low birth weight were risk factors for neonatal hypothyroidism (P<0.05). The combined use of TSH+FT4 levels and gestational age at birth resulted in an improved prediction of neonatal hypothyroidism and contributed to early therapeutic intervention. Thus, special intervention is necessary for pregnant women with thyroid dysfunction to reduce the incidence of neonatal hypothyroidism. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether uterine distention is associated with human pregnancy duration in a non-invasive observational setting., Design: Retrospective cohort study modelling uterine distention by interaction between maternal height and uterine load., Setting: The study is based on the 1990-2013 population data from all delivery units in Sweden., Participants: Uncomplicated first pregnancies of healthy Nordic-born mothers with spontaneous onset of labour. Pregnancies were classified as twin (n=2846) or singleton (n=527 868). Singleton pregnancies were further classified as carrying a large for gestational age fetus (LGA, n=24 286) or small for gestational age fetus (SGA, n=33 780)., Outcome Measures: Statistical interaction between maternal height and uterine load categories (twin vs singleton pregnancies, and LGA vs SGA singleton pregnancies), where the outcome is pregnancy duration., Results: In all models, statistically significant interaction was found. Mothers carrying twins had 2.9 times larger positive linear effect of maternal height on gestational age than mothers carrying singletons (interaction p=5e-14). Similarly, the effect of maternal height was strongly modulated by the fetal growth rate in singleton pregnancies: the effect size of maternal height on gestational age in LGA pregnancies was 2.1 times larger than that in SGA pregnancies (interaction p<1e-11). Preterm birth OR was 1.4 when the mother was short, and 2.8 when the fetus was extremely large for its gestational age; however, when both risk factors were present together, the OR for preterm birth was larger than expected, 10.2 (interaction p<0.0005)., Conclusions: Across all classes, maternal height was significantly associated with child's gestational age at birth. Interestingly, in short-statured women with large uterine load (twins, LGA), spontaneous delivery occurred much earlier than expected. The interaction between maternal height, uterine load size and gestational age at birth strongly suggests the effect of uterine distention imposed by fetal growth on birth timing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.)