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Reproductive Sciences (Thousand Oaks,... Jan 2020Cell-free fetal DNA in the maternal circulation has been associated with the onset of labor at term. Moreover, clinical studies have suggested that cell-free fetal DNA...
Cell-free fetal DNA in the maternal circulation has been associated with the onset of labor at term. Moreover, clinical studies have suggested that cell-free fetal DNA has value to predict pregnancy complications such as spontaneous preterm labor leading to preterm birth. However, a mechanistic link between cell-free fetal DNA and preterm labor and birth has not been established. Herein, using an allogeneic mouse model in which a paternal green fluorescent protein (GFP) can be tracked in the fetuses, we established that cell-free fetal DNA (Egfp) concentrations were higher in late gestation compared to mid-pregnancy and were maintained at increased levels during the onset of labor at term, followed by a rapid decrease after birth. A positive correlation between cell-free fetal DNA concentrations and the number of GFP-positive pups was also observed. The increase in cell-free fetal DNA concentrations prior to labor at term was not linked to a surge in any specific cytokine/chemokine; yet, specific chemokines (i.e., CCL2, CCL7, and CXCL2) increased as gestation progressed and maintained elevated levels in the postpartum period. In addition, cell-free fetal DNA concentrations increased prior to systemic inflammation-induced preterm birth, which was associated with a strong cytokine response in the maternal circulation. However, cell-free fetal DNA concentrations were not increased prior to intra-amniotic inflammation-induced preterm birth, but in this model, a mild inflammatory response was observed in the maternal circulation. Collectively, these findings suggest that an elevation in cell-free fetal DNA concentrations in the maternal circulation precedes the physiological process of labor at term and the pathological process of preterm labor linked with systemic inflammation, but not that associated with intra-amniotic inflammation.
Topics: Animals; Cell-Free Nucleic Acids; Chemokines; Cytokines; Female; Labor, Obstetric; Mice; Obstetric Labor, Premature; Parturition; Pregnancy; Premature Birth; Term Birth
PubMed: 32046392
DOI: 10.1007/s43032-019-00023-6 -
Endocrinology Feb 2019Despite decades of research in the field of human reproduction, the mechanisms responsible for human parturition still remain elusive. The objective of this study was to...
Despite decades of research in the field of human reproduction, the mechanisms responsible for human parturition still remain elusive. The objective of this study was to describe the changes in the exosomal miRNA concentrations circulating in the maternal plasma between mothers delivering term and preterm neonates, across gestation using a longitudinal study design. This descriptive study identifies the miRNA content in exosomes present in maternal plasma of term and preterm birth (PTB) (n = 20 and n = 10 per each gestational period, respectively) across gestation (i.e., first, second, and third trimesters and at the time of delivery). Changes in exosomal miRNA signature in maternal plasma during term and preterm gestation were determined using the NextSeq 500 high-output 75 cycles sequencing platform. A total of 167 and 153 miRNAs were found to significantly change (P < 0.05) as a function of the gestational age across term and PTB pregnancies, respectively. Interestingly, a comparison analysis between the exosomal miRNA profile between term and PTB reveals a total of 173 miRNAs that significantly change (P < 0.05) across gestation. Specific trends of changes (i.e., increase, decrease, and both) as a function of the gestational age were also identified. The bioinformatics analyses establish that the differences in the miRNA profile are targeting signaling pathways associated with TGF-β signaling, p53, and glucocorticoid receptor signaling, respectively. These data suggest that the miRNA content of circulating exosomes in maternal blood might represent a biomolecular "fingerprint" of the progression of pregnancy.
Topics: Case-Control Studies; Exosomes; Female; Gene Expression Profiling; Gestational Age; Humans; Longitudinal Studies; MicroRNAs; Pregnancy; Premature Birth; Term Birth; Young Adult
PubMed: 30358826
DOI: 10.1210/en.2018-00836 -
International Journal of Environmental... May 2021Preterm birth (PTB) and early term birth (ETB) are associated with high risks of perinatal mortality and morbidity. While extreme to very PTBs have been extensively...
Preterm birth (PTB) and early term birth (ETB) are associated with high risks of perinatal mortality and morbidity. While extreme to very PTBs have been extensively studied, studies on infants born at later stages of pregnancy, particularly late PTBs and ETBs, are lacking. In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes of PTB and ETB births in Qatar. We examined 15,865 singleton live births using 12-month retrospective registry data from the PEARL-Peristat Study. PTB and ETB incidence rates were 8.8% and 33.7%, respectively. PTB and ETB in-hospital mortality rates were 16.9% and 0.2%, respectively. Advanced maternal age, pre-gestational diabetes mellitus (PGDM), assisted pregnancies, and preterm history independently predicted both PTB and ETB, whereas chromosomal and congenital abnormalities were found to be independent predictors of PTB but not ETB. All groups of PTB and ETB were significantly associated with low birth weight (LBW), large for gestational age (LGA) births, caesarean delivery, and neonatal intensive care unit (NICU)/or death of neonate in labor room (LR)/operation theatre (OT). On the other hand, all or some groups of PTB were significantly associated with small for gestational age (SGA) births, Apgar < 7 at 1 and 5 min and in-hospital mortality. The findings of this study may serve as a basis for taking better clinical decisions with accurate assessment of risk factors, complications, and predictions of PTB and ETB.
Topics: Female; Humans; Incidence; Infant; Infant, Newborn; Pregnancy; Premature Birth; Qatar; Retrospective Studies; Risk Factors; Term Birth
PubMed: 34072575
DOI: 10.3390/ijerph18115865 -
Ultrasound in Obstetrics & Gynecology :... Jul 2021The aim of our study was two-fold. First, to evaluate the association between the change in the angle of progression (AoP) on maternal pushing and labor outcome. Second,...
OBJECTIVES
The aim of our study was two-fold. First, to evaluate the association between the change in the angle of progression (AoP) on maternal pushing and labor outcome. Second, to assess the incidence and clinical significance of the reduction of AoP on maternal pushing.
METHODS
This was a prospective cohort study of nulliparous women with singleton pregnancy at term. AoP was measured at rest and on maximum Valsalva maneuver before the onset of labor, and the difference between AoP on maximum Valsalva and that at rest (ΔAoP) was calculated for each woman. Following delivery and data collection, we assessed the association between ΔAoP and various labor outcomes, including Cesarean section (CS), duration of the first, second and active second stages of labor, Apgar score and admission to the neonatal intensive care unit (NICU). The prevalence of women with reduction of AoP on maximum Valsalva maneuver (AoP-regression group) was calculated and its association with the mode of delivery and duration of different stages of labor was assessed.
RESULTS
Overall, 469 women were included in the analysis. Among these, 273 (58.2%) had spontaneous vaginal birth, 65 (13.9%) had instrumental delivery and 131 (27.9%) underwent CS. Women in the CS group were older, had narrower AoP at rest and on maximum Valsalva, higher rate of epidural administration and lower 1-min and 5-min Apgar scores in comparison with the vaginal-delivery group. ΔAoP was comparable between the two groups. On Pearson's correlation analysis, AoP at rest and on maximum Valsalva maneuver had a significant negative correlation with the duration of the first stage of labor. ΔAoP showed a significant negative correlation with the duration of the active second stage of labor (Pearson's r, -0.125; P = 0.02). Cox regression model analysis showed that ΔAoP was associated independently with the duration of the active second stage (hazard ratio, 1.014 (95% CI, 1.003-1.025); P = 0.012) after adjusting for maternal age and body mass index. AoP reduction on maximum Valsalva was found in 73 (15.6%) women. In comparison with women who showed no change or an increase in AoP on maximum Valsalva, the AoP-regression group did not demonstrate significant difference in maternal characteristics, mode of delivery, rate of epidural analgesia, duration of the different stages of labor or rate of NICU admission.
CONCLUSIONS
In nulliparous women at term before the onset of labor, narrower AoP at rest and on maximum Valsalva, reflecting fetal head engagement, is associated with a higher risk of Cesarean delivery. The increase in AoP from rest to Valsalva, reflecting more efficient maternal pushing, is associated with a shorter active second stage of labor. Fetal head regression on maternal pushing is present in about 16% of women and does not appear to have clinical significance. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Adult; Apgar Score; Cesarean Section; Delivery, Obstetric; Female; Head; Humans; Infant, Newborn; Labor Onset; Labor Presentation; Labor, Obstetric; Pregnancy; Prospective Studies; Rest; Term Birth; Valsalva Maneuver
PubMed: 32730691
DOI: 10.1002/uog.22159 -
PloS One 2022Preterm birth (<37 weeks' gestation) is a risk factor for poor educational outcomes. A dose-response effect of earlier gestational age at birth on poor primary school...
Preterm birth (<37 weeks' gestation) is a risk factor for poor educational outcomes. A dose-response effect of earlier gestational age at birth on poor primary school attainment has been observed, but evidence for secondary school attainment is limited and focused predominantly on the very preterm (<32 weeks) population. We examined the association between gestational age at birth and academic attainment at the end of primary and secondary schooling in England. Data for children born in England from 2000-2001 were drawn from the population-based UK Millennium Cohort Study. Information about the child's birth, sociodemographic factors and health was collected from parents. Attainment on national tests at the end of primary (age 11) and secondary school (age 16) was derived from linked education records. Data on attainment in primary school was available for 6,950 pupils and that of secondary school was available for 7,131 pupils. Adjusted relative risks (aRRs) for these outcomes were estimated at each stage separately using modified Poisson regression. At the end of primary school, 17.7% of children had not achieved the expected level in both English and Mathematics and this proportion increased with increasing prematurity. Compared to full term (39-41 weeks) children, the strongest associations were among children born moderately (32-33 weeks; aRR = 2.13 (95% CI 1.44-3.13)) and very preterm (aRR = 2.06 (95% CI 1.46-2.92)). Children born late preterm (34-36 weeks) and early term (37-38 weeks) were also at higher risk with aRR = 1.18 (95% CI 0.94-1.49) and aRR = 1.21 (95% CI 1.05-1.38), respectively. At the end of secondary school, 45.2% had not passed at least five General Certificate of Secondary Education examinations including English and Mathematics. Following adjustment, only children born very preterm were at significantly higher risk (aRR = 1.26 (95% CI 1.03-1.54)). All children born before full term are at risk of poorer attainment during primary school compared with term-born children, but only children born very preterm remain at risk at the end of secondary schooling. Children born very preterm may require additional educational support throughout compulsory schooling.
Topics: Adolescent; Child; Cohort Studies; England; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Pregnancy; Premature Birth; Schools; Term Birth
PubMed: 35976808
DOI: 10.1371/journal.pone.0271952 -
Ginekologia Polska 2017Evaluate the time dependent expression of genes in preterm neonates and verify the influence of ontogenic maturation and the environmental factors on the gene expression...
OBJECTIVES
Evaluate the time dependent expression of genes in preterm neonates and verify the influence of ontogenic maturation and the environmental factors on the gene expression after birth.
MATERIAL AND METHODS
The study was carried out on 20 full-term newborns and 62 preterm newborns (mean birth weight = 1002 [g] (SD: 247), mean gestational age = 27.2 weeks (SD: 1.9)). Blood samples were drawn from all the study participants at birth and at the 36th week postmenstrual age from the preterm group to assess whole genome expression in umbilical cord blood and in peripheral blood leukocytes, respectively. (SurePrint G3 Human Gene Expression v3, 8x60K Microarrays (Agilent)).
RESULTS
A substantial number of genes was found to be expressed differentially at the time of birth and at 36 PMA in comparison to the term babies with more genes being down-regulated than up-regulated. However, the fold change in the majority of cases was < 2.0. Extremely preterm and very preterm infants were characterized by significantly down-regulated cytokine and chemokine related pathways. The number of down-regulated genes decreased and number of up-regulated genes increased at 36 PMA vs. cord blood. There were no specific gene expression pathway profiles found within the groups of different gestational ages.
CONCLUSIONS
Preterm delivery is associated with a different gene expression profile in comparison to term delivery. The gene expression profile changes with the maturity of a newborn measured by the gestational age.
Topics: Female; Gene Expression Profiling; Genome, Human; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Male; Pregnancy; Prospective Studies; Term Birth
PubMed: 28930370
DOI: 10.5603/GP.a2017.0080 -
The Cochrane Database of Systematic... Feb 2018Pregnant women with pre-existing diabetes (Type 1 or Type 2) have increased rates of adverse maternal and neonatal outcomes. Current clinical guidelines support elective... (Review)
Review
BACKGROUND
Pregnant women with pre-existing diabetes (Type 1 or Type 2) have increased rates of adverse maternal and neonatal outcomes. Current clinical guidelines support elective birth, at or near term, because of increased perinatal mortality during the third trimester of pregnancy.This review replaces a review previously published in 2001 that included "diabetic pregnant women", which has now been split into two reviews. This current review focuses on pregnant women with pre-existing diabetes (Type 1 or Type 2) and a sister review focuses on women with gestational diabetes.
OBJECTIVES
To assess the effect of planned birth (either by induction of labour or caesarean birth) at or near term gestation (37 to 40 weeks' gestation) compared with an expectant approach, for improving health outcomes for pregnant women with pre-existing diabetes and their infants. The primary outcomes relate to maternal and perinatal mortality and morbidity.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (15 August 2017), and reference lists of retrieved studies.
SELECTION CRITERIA
We planned to include randomised trials (including those using a cluster-randomised design) and non-randomised trials (e.g. quasi-randomised trials using alternate allocation) which compared planned birth, at or near term, with an expectant approach for pregnant women with pre-existing diabetes.
DATA COLLECTION AND ANALYSIS
Two of the review authors independently assessed study eligibility. In future updates of this review, at least two of the review authors will extract data and assess the risk of bias in included studies. We will also assess the quality of the evidence using the GRADE approach.
MAIN RESULTS
We identified no eligible published trials for inclusion in this review.We did identify one randomised trial which examined whether expectant management reduced the incidence of caesarean birth in uncomplicated pregnancies of women with gestational diabetes (requiring insulin) and with pre-existing diabetes. However, published data from this trial does not differentiate between pre-existing and gestational diabetes, and therefore we excluded this trial.
AUTHORS' CONCLUSIONS
In the absence of evidence, we are unable to reach any conclusions about the health outcomes associated with planned birth, at or near term, compared with an expectant approach for pregnant women with pre-existing diabetes.This review demonstrates the urgent need for high-quality trials evaluating the effectiveness of planned birth at or near term gestation for pregnant women with pre-existing (Type 1 or Type 2) diabetes compared with an expectant approach.
Topics: Cesarean Section; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Labor, Induced; Pregnancy; Pregnancy in Diabetics; Term Birth
PubMed: 29423911
DOI: 10.1002/14651858.CD012948 -
Environmental Health Perspectives Oct 2021Exposure to heat during pregnancy has been associated with reduced fetal growth. Less is known about associations with cold and the potential for critical time windows...
Low and High Ambient Temperatures during Pregnancy and Birth Weight among 624,940 Singleton Term Births in Israel (2010-2014): An Investigation of Potential Windows of Susceptibility.
BACKGROUND
Exposure to heat during pregnancy has been associated with reduced fetal growth. Less is known about associations with cold and the potential for critical time windows of exposure.
OBJECTIVES
We aimed to evaluate, in a national retrospective cohort, critical windows of susceptibility during pregnancy to extreme temperatures (low and high) and fetal growth, among 624,940 singleton term births in Israel during the period 2010-2014.
METHODS
Temperature exposures were estimated using a spatially refined gridded climate data set with a 1-h and resolution. Percentiles of temperature were categorized by climatic zone for the entire pregnancy and by trimesters and weeks. Generalized additive models with the distributed lag nonlinear model framework were used to estimate unadjusted and adjusted associations between percentiles and categories of temperature and fetal growth markers: term [births after 36 weeks of gestational age (GA)] mean birth weight and term low birth weight (tLBW, term infants with birth weight below ).
RESULTS
After adjustment, extreme temperatures (percentiles) during the entire pregnancy were associated with a lower mean birth weight { vs. 41st-50th percentile: [95% confidence interval (CI): , )]; vs. 41st-50th percentile: ; 95% CI: , }. Similar inverse U-shaped patterns were observed for all trimesters, with stronger associations for heat than for cold and for exposures during the third trimester. For heat, results suggest critical windows between 3-9 and 19-34 GA-weeks, with the strongest association estimated at 3 GA-weeks (temperature vs. 41st-50th percentiles: ; 95% CI: , ). For cold, there was a consistent trend of null associations early in pregnancy and stronger inverse associations over time, with the strongest association at 36 GA-week ( vs. 41st-50th percentiles: ; 95% CI: , ). For tLBW, U-shape patterns were estimated for the entire pregnancy and third trimester exposures, as well as nonsignificant associations with heat for 29-36 GA-weeks. Generally, the patterns of associations with temperatures during the entire pregnancy were consistent when stratified by urbanicity and geocoding hierarchy, when estimated for daily minimum and maximum temperatures, when exposures were classified based on temperature distributions in 49 natural regions, and when estimated for all live births.
DISCUSSION
Findings from our study of term live births in Israel (2010-2014) suggest that exposure to extreme temperatures, especially heat, during specific time windows may result in reduced fetal growth. https://doi.org/10.1289/EHP8117.
Topics: Birth Weight; Female; Hot Temperature; Humans; Israel; Pregnancy; Retrospective Studies; Temperature; Term Birth
PubMed: 34643443
DOI: 10.1289/EHP8117 -
The Journal of Maternal-fetal &... Dec 2024To assess pre-term birth, low birth-weight and growth restriction according to maternal thyroid screening results and subsequent treatment.
OBJECTIVE
To assess pre-term birth, low birth-weight and growth restriction according to maternal thyroid screening results and subsequent treatment.
METHODS
This is a nonintervention nested case-control study derived from 10,052 asymptomatic women previously screened during the first trimester marker with anti-thyroid peroxidase antibodies, serum thyroid stimulating hormone, and free thyroxine. Screening results had been classified as positive with one or more markers outside the normal range and referred to an endocrinologist. Cases were 512 women with positive results and information on recommended treatment: 204 thyroxine, propylthiouracil or surgery, and 308 no treatment or only iodine. Controls were a sequential sample of 1292 women with negative results. All cases and controls had information on gestation at delivery or birth-weight. Outcome measures were pre-term birth (<37 weeks), low birth-weight (<2.5 kg) and, for singletons, small for gestational age (SGA; <10th percentile).
RESULTS
Among singleton pregnancies, there was a higher prevalence of both pre-term birth (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.21-2.36, < .002) and low birth-weight (RR 1.72, 95% CI 1.13-2.62, < .02) in cases compared with controls. An increase in low birth-weight was also present in term pregnancies, but not significant (RR 1.80, 95% CI 0.78-4.14, = .16), and there was no difference in SGA prevalence (1.24, 95% CI 0.93-1.65, = .14). Among cases there was no significant difference in these rates according to treatment even after logistic regression, allowing for the individual screening marker levels and maternal weight.
CONCLUSIONS
Women with positive thyroid screening results are at increased risk of pre-term birth regardless of thyroid dysfunction or subsequent treatment. An association with low birth-weight is probably secondary to early delivery.
Topics: Pregnancy; Female; Humans; Thyroid Gland; Thyroxine; Case-Control Studies; Term Birth; Prenatal Diagnosis
PubMed: 38191240
DOI: 10.1080/14767058.2023.2300416 -
Advances in Nutrition (Bethesda, Md.) May 2019The role of both qualitative and quantitative early nutrient intakes on later health has been suggested for decades and supported by observational studies on humans,... (Review)
Review
The role of both qualitative and quantitative early nutrient intakes on later health has been suggested for decades and supported by observational studies on humans, mainly preterm and low-birth-weight infants, and animal models. However, to date, no comprehensive review has been conducted to evaluate the full impact of nutritional variables on healthy full-term infants. This umbrella review considers meta-analyses and systematic reviews on the health effects of different nutritional exposures or interventions in the first 2 y of life of healthy full-term infants in developed countries. The systematic reviews and meta-analyses published by March 2018 in MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews were included. The following outcomes were considered: growth and obesity, cardiovascular disease, neurodevelopment, allergy and autoimmunity, infections, and malignancy. Breastfeeding and complementary feeding were considered separately and analyzed by means of their differences in delivering heterogeneous food-related variables. The resulting data on the long-term effect of early nutritional differences in healthy full-term infants were found to be inconclusive. Only breastfeeding has a beneficial effect, which is nevertheless slight and limited to just a few outcome measures, whereas the type and duration required to be effective are still unclear. As regards the complementary feeding period, no clear effects of different dietary interventions emerge in terms of health outcomes. Available evidence on the health effects of differences in early nutrition in healthy full-term infants still remains largely inconclusive.
Topics: Child, Preschool; Developed Countries; Eating; Female; Humans; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Male; Meta-Analysis as Topic; Nutrients; Systematic Reviews as Topic; Term Birth; Time Factors
PubMed: 30843039
DOI: 10.1093/advances/nmy106