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"Gestational age at birth"
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Vaginal Microbiome Composition in Early Pregnancy and Risk of Spontaneous Preterm and Early Term Birth Among African American Women
by
Satten, Glen A.
,
Hill, Cherie C.
,
Corwin, Elizabeth J.
in
Actinobacteria
,
African Americans
,
Birth
2021
To evaluate the association between the early pregnancy vaginal microbiome and spontaneous preterm birth (sPTB) and early term birth (sETB) among African American women.
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).
Nearly half of the women had a vaginal microbiome classified as CST IV (Diverse CST), while one-third had CST III (
dominated) and just 16% had CST I, II, or V (non-iners
dominated). Compared to vaginal CST I, II, or V (non-iners
dominated), both CST III (
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
(p=0.011), non-iners
(p=0.016), and
(p=0.035) and the presence of
(p=0.049), BVAB2 (p=0.024),
(p=0.011), and
(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%.
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.
Journal Article
Stress and anxiety during pregnancy and length of gestation: a federated study using data from five Canadian and European birth cohorts
by
Fortier, Isabel
,
Nader, Johanna
,
Harris, Jennifer R.
in
Adult
,
Anxiety
,
Anxiety - epidemiology
2024
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.
Journal Article
Distinct maternal DNA methylation associations with gestational age at early and late-mid term pregnancy in a low- and middle-income country: evaluation of biological, genetic, and psychosocial contributors
by
Premji, Shahirose Sadrudin
,
Kobor, Michael S.
,
Konwar, Chaini
in
Adult
,
Cell cycle
,
Childbirth & labor
2025
Mothers undergo physiological and molecular changes over the course of gestation. These modifications “get under the skin” and may be reflected in the maternal epigenome through processes such as DNA methylation. Such an epigenetic mark may offer insights into maternal responses to prenatal influences and biological cues from the developing fetus, thereby functioning as an indirect indicator of the conditions the fetus experiences in utero. We measured whole blood DNA methylation using the MethylationEPIC BeadChip Infinium microarray v1.0 in 22 pregnant women from Pakistan, a low- and middle-income country (LMIC), at two timepoints during their term pregnancies (early: 10–19 weeks and late-mid: 22–29 weeks). We used DNA methylation profiles to predict immune cell proportions and tested differences in these proportions and DNA methylation patterns between the two timepoints. Further, we evaluated DNA methylation associations with gestational age at each timepoint and examined the contribution of genetic, psychosocial, and biological factors. Our analyses documented changes in immune cell proportions and DNA methylation profiles over the course of gestation, albeit in a small percentage of the measured DNA methylome. We also observed timepoint-specific DNA methylation associations with gestational age, predominantly at early pregnancy, with predicted interleukin-6 level and socioeconomic status contributing to a few of these associations. On comparing to three external cohorts from different sociocultural contexts, we also noted these signatures to be unique to LMIC settings. Overall, these changes measured in term pregnancies may be used to assess both fluctuations in pregnancy and birth outcomes, particular in women from LMIC settings.
Journal Article
Consistent cord blood DNA methylation signatures of gestational age between South Asian and white European cohorts
by
Cawte, Nathan
,
Deng, Wei Q.
,
Morrison, Katherine M.
in
Accelerated gestational age
,
Adult
,
Asian People - genetics
2024
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.
Journal Article
Mapping the critical gestational age at birth that alters brain development in preterm-born infants using multi-modal MRI
by
Skranes, Jon
,
Oishi, Kumiko
,
Akazawa, Kentaro
in
Attention deficit hyperactivity disorder
,
Automation
,
Brain
2017
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.
•Diffusion tensor and T2-mapping MRI was measured from preterm and term-born infants.•Change point analysis detects critical gestational age at birth (GAB) in 126 brain regions.•Change-points maps revealed spatiotemporal order of structural development.•GAB-dependent MRI change reflected brain prematurity and postnatal development.
Journal Article
Uterine distention as a factor in birth timing: retrospective nationwide cohort study in Sweden
by
Adams Waldorf, Kristina M
,
Zhang, Ge
,
Jacobsson, Bo
in
Clinical Medicine
,
Cohort analysis
,
Cytokines
2018
ObjectivesTo determine whether uterine distention is associated with human pregnancy duration in a non-invasive observational setting.DesignRetrospective cohort study modelling uterine distention by interaction between maternal height and uterine load.SettingThe study is based on the 1990–2013 population data from all delivery units in Sweden.ParticipantsUncomplicated 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 measuresStatistical interaction between maternal height and uterine load categories (twin vs singleton pregnancies, and LGA vs SGA singleton pregnancies), where the outcome is pregnancy duration.ResultsIn 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).ConclusionsAcross 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.
Journal Article
A meta‐analysis showing the effect of surgical site wound infections and associated risk factors in neonatal surgeries
by
Abdelrahim, Mohamed EA
,
Abdelgawad, Mohamed A.
,
Parambi, Della G.T.
in
Antibiotic Prophylaxis
,
Antibiotics
,
Bias
2022
A meta‐analysis was performed to assess the effect of surgical site wound infections and risk factors in neonates undergoing surgery. A systematic literature search up to January 2022 incorporated 17 trials involving 645 neonates who underwent surgery at the beginning of the trial; 198 of them had surgical site wound infections, and 447 were control for neonates. The statistical tools like the dichotomous or continuous method used within a random or fixed‐influence model to establish the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to evaluate the risk factors and influence of surgical site wound infections in neonates undergoing surgery. Surgical site wound infections had significantly higher mortality with OR value 2.03 at 95% CI 1.40–2.95 with P‐value <0.001, the longer length of hospital stay (MD, 31.88; 95% CI, 18.17–45.59, P < 0.001), and lower birthweight of neonates (MD, −0.30; 95% CI, −0.53 to −0.07, P = 0.01) compared with neonates with no surgical site wound infections undergoing surgery. However, no remarkable change was observed with surgical site wound infections in the gestational age at birth of neonates (MD, −0.70; 95% CI, −1.46 to 0.05, P = 0.07), and the preoperative antibiotic prophylaxis (OR, 1.28; 95% CI, 0.57–2.87, P = 0.55) compared with no surgical site wound infections for neonates undergoing surgery. Surgical site wound infections had significantly higher mortality, a longer length of hospital stay, and lower birthweight of neonates. However, they had no statistically significant difference in the gestational age at birth of neonates and the preoperative antibiotic prophylaxis compared with no surgical site wound infections for neonates undergoing surgery. Furthermore, evidence is needed to confirm the outcomes.
Journal Article
Correlations of Aflatoxin Exposure from Cooking Oil and Dietary Foods During Pregnancy with Birth Weight and Gestational Age at Birth in Guangxi, China
2024
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.
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.
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.
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.
Journal Article
Association between gestational age at birth, antenatal corticosteroids, and outcomes at 5 years: multiple courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5)
by
Armson, Anthony
,
Gafni, Amiram
,
Amankwah, Kofi
in
Adult
,
Betamethasone - administration & dosage
,
Betamethasone - adverse effects
2014
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.
Trial registration
This study has been registered at (identifier
NCT00187382
)
Journal Article
Gestational age at birth in pregnancies with antenatal corticosteroid administration in relation to risk factors: a retrospective cohort study
by
Abele, Harald
,
Graf, Joachim
,
Pauluschke-Fröhlich, Jan
in
Abortion
,
extreme immaturity
,
Gestational age
2024
The 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 < 260 days) and extreme immaturity (gestational age < 196 days) in relation to several diagnoses (PPROM, placental bleeding, premature labor, preeclampsia, oligohydramnios, amniotic infection syndrome (AIS), cervical insufficiency) and risk factors (age > 35, history of preterm delivery, multifetal gestation, gestational diabetes, hypertension, nicotine abuse).
The 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).
In total,
= 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).
There is a need for further research in order to be able to apply therapeutic measures more accurately in relation to risk factors and diagnoses.
Journal Article