Mother-newborn Pairs Research Articles

BDNF and KISS-1 Levels in Maternal Serum, Umbilical Cord, and Placenta: The Potential Role of Maternal Levels as Effect Biomarker

Brain-derived neurotrophic factor (BDNF) and kisspeptin-1 (KISS-1) regulate placental development and fetal growth. The predictive value of maternal serum BDNF and KISS-1 concentrations for placental and umbilical cord levels has not yet been explored. The influence of prenatal lead (Pb) and cadmium (Cd) exposure and maternal iron status on BDNF and KISS-1 levels is also unclarified and of concern. In a pilot cross-sectional study with 65 mother–newborn pairs, we analyzed maternal and cord serum levels of pro-BDNF, mature BDNF, and KISS-1, BDNF, and KISS-1 gene expression in placenta, Pb and Cd in maternal and umbilical cord blood (erythrocytes), and placenta. We conducted a series of in vitro experiments using human primary trophoblast cells (hTCs) and BeWo cells to verify main findings of the epidemiological analysis. Strong and consistent correlations were observed between maternal serum levels of pro-BDNF, mature BDNF, and KISS-1 and corresponding levels in umbilical serum and placental tissue. Maternal red blood cell Pb levels were inversely correlated with serum and placental KISS-1 levels. Lower expression and release of KISS-1 was also observed in Pb-exposed BeWo cells. In vitro Pb exposure also reduced cellular BDNF levels. Cd-treated BeWo cells showed increased pro-BDNF levels. Low maternal iron status was positively associated with low BDNF levels. Iron-deficient hTCs and BeWo cells showed a consistent decrease in the release of mature BDNF. The correlations between maternal BDNF and KISS-1 levels, placental gene expression, and umbilical cord serum levels, respectively, indicate the strong potential of maternal serum as predictive matrix for BDNF and KISS-1 levels in placentas and fetal sera. Pb exposure and iron status modulate BDNF and KISS-1 levels, but a clear direction of modulations was not evident. The associations need to be confirmed in a larger sample and validated in terms of placental and neurodevelopmental function.

Associations of self-reported sleep duration and sleep quality during pregnancy with newborn telomere length

BackgroundTelomere length (TL) at birth is considered a potential biomarker for lifelong health. Although maternal sleep disturbance has been linked to a series of adverse pregnancy outcomes, evidence on the effect of maternal sleep on newborn TL remains scarce. Therefore, we aim to investigate the association of maternal sleep duration and sleep quality with newborn TL. MethodsA total of 742 mother-newborn pairs were recruited from Wuhan Children’s Hospital between November 2013 and March 2015. Cord blood TL was measured using real-time quantitative polymerase chain reaction. Maternal sleep duration and quality during late pregnancy were obtained via questionnaires. Multivariate linear regression models were used to estimate the effects of maternal sleep duration and sleep quality on newborn TL. ResultsA total of 742 maternal-newborn pairs were included in the analyses. Mothers sleeping ≥10 hours had a 9.30% (95% CI: 2.09%, 15.99%) shorter newborn TL than those sleeping 7-<9 hours. However, the association in mothers with short sleep duration (<7 hours) did not reach statistical significance. Compared to mothers with good sleep quality, those with poor sleep quality had a 9.91% (95% CI: 4.06%, 15.40%) shorter newborn TL. We observed a joint effect of sleep duration and sleep quality on newborn telomere shortening. Women with sleep duration ≥10 hours and poor sleep quality were most likely to have newborns with short TL (percent change:−19.66%, 95% CI: −28.42, −9.84%). ConclusionsLong sleep duration and poor sleep quality during late pregnancy were associated with shorter newborn TL.

Prenatal exposure to per- and polyfluoroalkyl substances and pregnancy outcome in Austria

Per- and polyfluoroalkyl substances (PFAS) are a large group of persistent industrial chemicals that can harm reproductive health. PFAS levels were analysed to determine the current sources of exposure and possible associations between prenatal PFAS exposure and adverse pregnancy outcome. Samples from 136 mother-newborn pairs recruited between 2017 and 2019 were analysed for the presence of 31 target PFAS in maternal serum, umbilical cord serum, and placental tissue by high-performance liquid chromatography coupled to a tandem mass spectrometer. Questionnaires and medical records were used to survey sources of exposure and pregnancy outcome, including small for gestational age (SGA), fetal growth restriction (FGR), preeclampsia (PE), preterm birth, large for gestational age (LGA) and gestational diabetes mellitus (GDM). Data were analysed for individual PFAS and sum4PFAS (sum of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) serum levels) in logistic regression analyses and categorical regression analyses. Compared to data from a previous Viennese study in 2010–12, sum4PFAS levels were generally lower. Sum4PFAS serum levels of three women (2.2%) exceeded 6.9 µg/L, a level that corresponds to the recently established tolerable weekly intake (TWI) of EFSA for nursing mothers aged 35 years; in the 2010/2012 study it was 13.6%. The large contribution of unidentified extractable organofluorine (EOF) fractions to total PFAS exposure is a concern. Study site, mean maternal corpuscular hemoglobin (MCH), use of facial lotion, and owning upholstered furniture were significantly influencing maternal exposure. While no effect of sum4PFAS on pregnancy outcome could be detected, we found highest placental PFDA levels in SGA births. PFHxS levels in umbilical cord and placenta were highest in preterm births. Further studies are needed to elucidate the relationship of prenatal PFAS exposure and pregnancy outcome, in particular to confirm whether and how placental PFDA levels may contribute to an increased risk for SGA.

Effect of fetal malposition, primiparous, and premature rupture of membrane on Neonatal Near miss mediated by grade three meconium-stained amniotic fluids and duration of the active first stage of labor: Mediation analysis.

In many low-income countries, including Ethiopia, neonatal mortality remains a major concern. For every newborn that dies, many more neonates survived (near-miss neonates) the first 28 days after birth from life-threatening conditions. The generation of evidence on neonatal near-miss determinants could be a critical step in reducing neonatal mortality rates. However, studies causal pathway determinants are limited in Ethiopia. This study aimed to investigate the Neonatal Near-miss determinants in public health hospitals in Amhara Regional State, northwest Ethiopia. A cross-sectional study was conducted on 1277 mother-newborn pairs at six hospitals between July 2021 and January 2022. A validated interviewer-administered questionnaire and a review of medical records were used to collect data. Data were entered into Epi-Info version 7.1.2 and exported to STATA version 16 in California, America for analysis. The paths from exposure variables to Neonatal Near-Miss via mediators were examined using multiple logistic regression analysis. The adjusted odds ratio (AOR) and ß-coefficients were calculated and reported with a 95% confidence interval and a p-value of 0.05. The proportion of neonatal near-misses was 28.6% (365/1277) (95% CI: 26-31%). Women who could not read and write (AOR = 1.67,95%CI:1.14-2.47), being primiparous (AOR = 2.48,95% CI:1.63-3.79), pregnancy-induced hypertension (AOR = 2.10,95% CI:1.49-2.95),being referred from other health facilities (AOR = 2.28,95% CI:1.88-3.29), premature rupture of membrane (AOR = 1.47,95% CI:1.09-1.98), and fetal malposition (AOR = 1.89,95% CI:1.14-3.16) were associated with Neonatal Near-miss. Grade III meconium stained amniotic fluid partially mediated the relationship between primiparous (ß = 0.517), fetal malposition (ß = 0.526), pregnant women referred from other health facilities (ß = 0.948) and Neonatal Near-Miss at P-value < 0.01. Duration of the active first stage of labour partially mediated the relationship between primiparous (ß = -0.345), fetal malposition (ß = -0.656), premature rupture of membranes (ß = -0.550) and Neonatal Near-Miss at P- value <0.01.It had also a significant indirect effect (ß = 0.581, P<0.001) on NNM with variables (primiparous, fetal malposition, and premature rupture of membranes). The relationship between fetal malposition, primiparous, referred from other health facilities, premature rupture of membrane, and Neonatal Near miss were partially mediated by grade III meconium stained amniotic fluid and duration of the active first stage of labour. Early diagnosis of these potential danger signs and appropriate intervention could be of supreme importance in reducing NNM.

Do we know how to supplement selenium in pregnancy to provide a proper micronutrient status for mother-newborn pairs?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator

BackgroundIn utero exposure to diabetes has been shown to contribute to preterm birth, though the underlying biological mechanisms are yet to be fully elucidated. Fetal epigenetic variations established in utero may be a possible pathway. This study aimed to investigate whether in utero exposure to diabetes was associated with a change in newborn DNA methylation, and whether the identified CpG sites mediate the association between diabetes and preterm birth in a racially diverse birth cohort population.MethodsThis study included 954 mother–newborn pairs. Methylation levels in the cord blood were determined using the Illumina Infinium MethylationEPIC BeadChip 850 K array platform. In utero exposure to diabetes was defined by the presence of maternal pregestational or gestational diabetes. Preterm birth was defined as gestational age at birth less than 37 weeks. Linear regression analysis was employed to identify differentially methylated CpG sites. Differentially methylated regions were identified using the DMRcate Package.Results126 (13%) newborns were born to mothers with diabetes in pregnancy and 173 (18%) newborns were born preterm, while 41 newborns were born both preterm and to mothers with diabetes in pregnancy. Genomic-wide CpG analysis found that eighteen CpG sites in cord blood were differentially methylated by maternal diabetes status at an FDR threshold of 5%. These significant CpG sites were mapped to 12 known genes, one of which was annotated to gene Major Histocompatibility Complex, Class II, DM Beta (HLA-DMB). Consistently, one of the two identified significant methylated regions overlapped with HLA-DMB. The identified differentially methylated CpG sites mediated the association between diabetes in pregnancy and preterm birth by 61%.ConclusionsIn this US birth cohort, we found that maternal diabetes was associated with altered fetal DNA methylation patterns, which substantially explained the link between diabetes and preterm birth.

Trimester-specific associations of maternal exposure to bisphenols with neonatal thyroid stimulating hormone levels: A birth cohort study

BackgroundGrowing evidence suggests that exposure to bisphenol A (BPA) during pregnancy could interfere with neonatal thyroid function. Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as the substitutes of BPA. However, little is known about the effects of maternal exposure to BPS and BPF on neonatal thyroid function. The current study was aimed to investigate the trimester-specific associations of maternal exposure to BPA, BPS, and BPF with neonatal thyroid stimulating hormone (TSH) levels. MethodsBetween November 2013 and March 2015, a total of 904 mother-newborn pairs were recruited from the Wuhan Healthy Baby Cohort Study, providing maternal urine samples in the first, second, and third trimesters for bisphenol exposure assessment, and neonatal heel prick blood samples for TSH measurement. Multiple informant model and quantile g-computation were used to evaluate the trimester-specific associations of bisphenols individually and mixture with TSH, respectively. ResultsEach doubling concentration increase of maternal urinary BPA in the first trimester was significantly related to a 3.64 % (95% CI: 0.84 %, 6.51 %) increment in neonatal TSH. Each doubling concentration increase of BPS in the first, second and third trimesters were associated with 5.81 % (95 % CI: 2.27 %, 9.46 %), 5.70 % (95 % CI: 1.99 %, 9.55 %), 4.36 % (95 % CI: 0.75 %, 8.11 %) higher neonatal blood TSH, respectively. No significant association between trimester-specific BPF concentration and TSH was observed. The relationships between exposures to BPA/BPS and neonatal TSH were more evident in female infants. Quantile g-computation indicated that maternal co-exposure to bisphenols in the first trimester was significantly associated with neonatal TSH levels in a non-linear fashion. ConclusionMaternal exposure to BPA and BPS were positively associated with neonatal TSH levels. The results indicated the endocrine disrupting effect of prenatal exposure to BPS and BPA, which should be of particular concern.

Prenatal Exposure to Air Pollution and Pre-Labor Rupture of Membranes in a Prospective Cohort Study: The Role of Maternal Hemoglobin and Iron Supplementation.

Exposure to air pollution in prenatal period is associated with prelabor rupture of membranes (PROM). However, the sensitive exposure time windows and the possible biological mechanisms underlying this association remain unclear. We aimed to identify the sensitive time windows of exposure to air pollution for PROM risk. Further, we examined whether maternal hemoglobin levels mediate the association between exposure to air pollution and PROM, as well as investigated the potential effect of iron supplementation on this association. From 2015 to 2021, 6,824 mother-newborn pairs were enrolled in the study from three hospitals in Hefei, China. We obtained air pollutant data [particulate matter (PM) with aerodynamic diameter (), PM with aerodynamic diameter (), sulfur dioxide (), and carbon monoxide (CO)] from the Hefei City Ecology and Environment Bureau. Information on maternal hemoglobin levels, gestational anemia, iron supplementation, and PROM was obtained from medical records. Logistic regression models with distributed lags were used to identify the sensitive time window for the effect of prenatal exposure to air pollutant on PROM. Mediation analysis estimated the mediated effect of maternal hemoglobin in the third trimester, linking prenatal air pollution with PROM. Stratified analysis was used to investigate the potential effect of iron supplementation on PROM risk. We found significant association between prenatal exposure to air pollution and increased PROM risk after adjusting for confounders, and the critical exposure windows of , , and CO were the 21th to 24th weeks of pregnancy. Every increase in and , increase in , and increase in CO was associated with low maternal hemoglobin levels [ (95% confidence interval (CI): , ), (95% CI: , ), (95% CI: , ), and (95% CI: , ), respectively] in the third trimester. The proportion of the association between air pollution and PROM risk mediated by hemoglobin levels was 20.61% [average mediation effect (95% CI): 0.02 (0.01, 0.05); average direct effect (95%): 0.08 (0.02, 0.14)]. The PROM risk associated with exposure to low-medium air pollution could be attenuated by maternal iron supplementation in women with gestational anemia. Prenatal exposure to air pollution, especially in the 21st to 24th weeks of pregnancy, is associated with PROM risk, which is partly mediated by maternal hemoglobin levels. Iron supplementation in anemia pregnancies may have protective effects against PROM risk associated with exposure to low-medium air pollution. https://doi.org/10.1289/EHP11134.

Reliability and validity of the Japanese version of the Infant Breastfeeding Assessment Tool

ObjectiveTo translate the Infant Breastfeeding Assessment Tool (IBFAT) into Japanese and confirm the reliability and validity of the Japanese version of IBFAT. DesignThe methodological study examining the reliability and validity of the Japanese version of the IBFAT. SettingA maternity hospital in Tokyo. ParticipantsTen mother-newborn pairs were recruited for the reliability analysis. 101 mother-newborn pairs were recruited for the validity analysis. Measurements and findingsReliability was verified by video recording and direct observation. The observers are one researcher, and 11 evaluators consisting of midwives and nurses. Amongst the 11 evaluators, six evaluators directly observed breastfeeding behaviours and five evaluators observed breastfeeding behaviours through video viewing. Regarding the inter-rater agreement, the intraclass correlation (ICC) between the researcher and six direct evaluators was 0.985 (95% confidence interval [CI]: 0.941–0.996) and that amongst five video viewing evaluators was 0.827 (95% CI: 0.647–0.945). In the intra-rater agreement, the lowest ICC amongst all those investigating IBFAT scores was 0.810 (95% CI: 0.433–0.948). In concurrent validity, the correlation coefficients between the IBFAT and Breastfeeding behaviour Assessment (BBA) scores on the first day after birth and the fourth or fifth day after birth (at discharge) were 0.66 (p < 0.001) and 0.40 (p < 0.001), respectively. In predictive validity, the medians and interquartile ranges (IQRs) of IBFAT scores at discharge were 11.0 (IQR: 11.0–12.0) and 11.0 (IQR: 11.0–12.0) for the breast and mixed milk groups at one-month check-up, respectively. While both median values were the same, the Mann-Whitney U test showed a significant difference. Key conclusionsThe Japanese version of the IBFAT is valid and reliable for measuring feeding behaviour amongst newborns in the first week of life. Implications for practiceThe Japanese version of the IBFAT can be available both in a clinical setting and in research to help support breastfeeding.

Sex differences in the intergenerational link between maternal and neonatal whole blood DNA methylation: a genome-wide analysis in 2 birth cohorts

BackgroundThe mother–child inheritance of DNA methylation (DNAm) variations could contribute to the inheritance of disease susceptibility across generations. However, no study has investigated patterns of mother–child associations in DNAm at the genome-wide scale. It remains unknown whether there are sex differences in mother–child DNAm associations.ResultsUsing genome-wide DNAm profiling data (721,331 DNAm sites, including 704,552 on autosomes and 16,779 on the X chromosome) of 396 mother–newborn pairs (54.5% male) from the Boston Birth Cohort, we found significant sex differences in mother–newborn correlations in genome-wide DNAm patterns (Spearman’s rho = 0.91–0.98; p = 4.0 × 10–8), with female newborns having stronger correlations. Sex differences in correlations were attenuated but remained significant after excluding X-chromosomal DNAm sites (Spearman’s rho = 0.91–0.98; p = 0.035). Moreover, 89,267 DNAm sites (12.4% of all analyzed, including 88,051 [12.5% of analyzed] autosomal and 1,216 [7.2% of analyzed] X-chromosomal sites) showed significant mother–newborn associations in methylation levels, and the top autosomal DNAm sites had high heritability than the genome-wide background (e.g., the top 100 autosomal DNAm sites had a medium h2 of 0.92). Additionally, significant interactions between newborn sex and methylation levels were observed for 11 X-chromosomal and 4 autosomal DNAm sites that were mapped to genes that have been associated with sex-specific disease/traits or early development (e.g., EFHC2, NXY, ADCYAP1R1, and BMP4). Finally, 18,769 DNAm sites (14,482 [77.2%] on the X chromosome) showed mother–newborn differences in methylation levels that were significantly associated with newborn sex, and the top autosomal DNAm sites had relatively small heritability (e.g., the top 100 autosomal DNAm sites had a medium h2 of 0.23). These DNAm sites were mapped to 2,532 autosomal genes and 978 X-chromosomal genes with significant enrichment in pathways involved in neurodegenerative and psychological diseases, development, neurophysiological process, immune response, and sex-specific cancers. Replication analysis in the Isle of Wight birth cohort yielded consistent results.ConclusionIn two independent birth cohorts, we demonstrated strong mother–newborn correlations in whole blood DNAm on both autosomes and ChrX, and such correlations vary substantially by sex. Future studies are needed to examine to what extent our findings contribute to developmental origins of pediatric and adult diseases with well-observed sex differences.

First Comparative Evaluation of Short-Chain Fatty Acids and Vitamin-K-Dependent Proteins Levels in Mother-Newborn Pairs at Birth.

The interplay between vitamin K (vitK) (as carboxylation cofactor, partially produced by the gut microbiota) and short-chain fatty acids (SCFAs), the end-product of fiber fermentation in the gut, has never been assessed in mother-newborn pairs, although newborns are considered vitK deficient and with sterile gut. We collected venous blood from 45 healthy mothers with uncomplicated term pregnancies and umbilical cord blood from their newborns at birth. The concentrations of total SCFAs and hepatic/extra-hepatic vitK-dependent proteins (VKDPs), as proxies of vitK status were assayed: undercarboxylated and total matrix Gla protein (ucMGP and tMGP), undercarboxylated osteocalcin (ucOC), undercarboxylated Gla-rich protein (ucGRP), and protein induced by vitK absence II (PIVKA-II). We found significantly higher ucOC (18.6-fold), ucMGP (9.2-fold), and PIVKA-II (5.6-fold) levels in newborns, while tMGP (5.1-fold) and SCFAs (2.4-fold) were higher in mothers, and ucGRP was insignificantly modified. In mother-newborn pairs, only ucGRP (r = 0.746, p < 0.01) and SCFAs (r = 0.428, p = 0.01) levels were correlated. Conclusions: We report for the first time the presence of SCFAs in humans at birth, probably transferred through the placenta to the fetus. The increased circulating undercarboxylated VKDPSs in newborns revealed a higher vitamin K deficiency at the extrahepatic level compared to liver VKDPs.

Maternal 25(OH)D attenuates the relationship between ambient air pollution during pregnancy and fetal hyperinsulinism

Inflammatory responses have been demonstrated to link air pollution with insulin resistance and type 2 diabetes in adults. However, few studies have focused on the relationship between prenatal air pollution and fetal β-cell function and the mediating effect of systematic inflammation remains elusive. Whether the anti-inflammatory effect of vitamin D could attenuate the β-cell dysfunction in early life warrants further investigations. We aimed to determine whether maternal blood 25(OH)D attenuates the associations of ambient air pollution during pregnancy with fetal hyperinsulinism mediated by maternal inflammatory response. A total of 8250 mother-newborn pairs were included between 2015 and 2021 in the Maternal & Infants Health in Hefei study. Weekly mean air pollution exposure to fine particles (PM2.5 and PM10), SO2, and CO was estimated across pregnancy. Maternal serum samples in the third trimester were used to measure the high-sensitivity c-reactive protein (hs-CRP) and 25(OH)D. Cord blood samples at delivery were collected for the measurement of C-peptide. Fetal hyperinsulinism was based on cord C-peptide >90th centile. An increased fetal hyperinsulinism risk was associated with per 10 μg/m3 increase in PM2.5 [odds ratios (OR): 1.45 (95% confidence interval (CI):1.32, 1.59)], per 10 μg/m3 increase in PM10 [OR = 1.49 (95% CI:1.37, 1.63)], per 5 μg/m3 increase in SO2 [OR = 1.91 (95% CI: 1.70, 2.15)], and per 0.1 mg/m3 increase in CO [OR = 1.48 (95% CI:1.37, 1.61)] across pregnancy. Mediation analysis showed a 16.3% contribution of maternal hsCRP to the relationship between air pollution throughout pregnancy and fetal hyperinsulinism. Air pollution-associated higher levels of hsCRP and risk of fetal hyperinsulinism could be attenuated by higher maternal 25(OH)D levels. Prenatal ambient air pollution exposures were associated with an increased fetal hyperinsulinism risk mediated by maternal serum hsCRP. Higher antenatal 25(OH)D levels could attenuate air pollution-induced inflammatory responses and hyperinsulinism risk.

Mediating effect of endocrine hormones on association between per- and polyfluoroalkyl substances exposure and birth size: Findings from sheyang mini birth cohort study

BackgroundPrenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to affect fetus growth, but current results were inconsistent and their mechanism remained unclear. ObjectivesWe aimed to evaluate the associations of prenatal exposure to single and/or multiple PFAS with birth size and to elucidate whether thyroid hormones and reproductive hormones mediate these associations. MethodsA total of 1087 mother-newborn pairs from Sheyang Mini Birth Cohort Study were included in the present cross-sectional analysis. 12 PFAS, 5 thyroid hormones and 2 reproductive hormones were measured in cord serum. Multiple linear regression models and Bayesian kernel machine regression (BKMR) models were used to examine the associations of PFAS with either birth size or endocrine hormones. One-at-a-time pairwise mediating effect analysis was applied to estimate the mediating effect of single hormone in the association between individual chemical and birth size. High-dimensional mediation approach including elastic net regularization and Bayesian shrinkage estimation were further performed to reduce exposure dimension and figure out the global mediation effects of joint endocrine hormones. ResultsPerfluorononanoic acid (PFNA) exposure was positively associated to weight for length z score [WLZ, per log10-unit: regression coefficient (β) = 0.26, 95% confidence intervals (CI): 0.04, 0.47] and ponderal index (PI, β = 0.56, 95% CI: 0.09, 1.02), and PFAS mixture results fit by BKMR model showed consistent consequences. High-dimensional mediating analyses revealed that thyroid stimulating hormone (TSH) explained 6.7% of the positive association between PFAS mixtures exposure and PI [Total effect (TE) = 1.499 (0.565, 2.405); Indirect effect (IE) = 0.105 (0.015, 0.231)]. Besides, 7.3% of the PI variance was indirectly explained by 7 endocrine hormones jointly [TE = 0.810 (0.802, 0.819); IE = 0.040 (0.038, 0.041)]. ConclusionsPrenatal PFAS mixtures exposure, especially PFNA, was positively associated to birth size. Such associations were partly mediated by cord serum TSH.

The influence of pre-gestational nutritional status on mother-newborn pair outcomes

Introduction: Abnormal pregestational and gestational maternal nutritional status is an undeniable health problem which can result in gestational changes and interfere in fetal and maternal health conditions. Objective: To analyze the influence of pre-pregnancy nutritional status on mother-newborn pair outcomes. Methods: This is an observational, analytical, and cross-sectional study carried out in a public Maternity Hospital in Joinville, SC, Brazil. A total of 1,670 puerperal women were interviewed and classified according to BMI. The outcomes evaluated were: cesarean delivery, Gestational Diabetes Mellitus, Pregnancy-induced Hypertension, small for Gestational age newborns, large for gestational age newborns, premature birth, low weight at birth and admission to the neonatal intensive care unit. Results: Low-weight pregnant women had a higher risk of cesarian delivery. Overweight and obese patients had a greater chance of GDM, with the odds ranging from 1.5 to 7.2 times, and PIH with the odds ranging from 1.7 to 4.6 times. Conclusion: Low-weight pregnant women have a higher chance of cesarian delivery. Meanwhile, overweight and all classes of obesity in pregnancy progressively increase the risk of GDM and PIH.

Machine Learning-based Classifiers for the Prediction of Low Birth Weight.

Low birth weight (LBW) is a global concern associated with fetal and neonatal mortality as well as adverse consequences such as intellectual disability, impaired cognitive development, and chronic diseases in adulthood. Numerous factors contribute to LBW and vary based on the region. The main objectives of this study were to compare four machine learning classifiers in the prediction of LBW and to determine the most important factors related to this phenomenon in Hamadan, Iran. We carried out a retrospective cross-sectional study on a dataset collected from Fatemieh Hospital in 2017 that included 741 mother-newborn pairs and 13 potential factors. Decision tree, random forest, artificial neural network, support vector machine, and logistic regression (LR) methods were used to predict LBW, with five evaluation criteria utilized to compare performance. Our findings revealed a 7% prevalence of LBW. The average accuracy of all models was 87% or higher. The LR method provided a sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and accuracy of 74%, 89%, 7.04%, 29%, and 88%, respectively. Using LR, gestational age, number of abortions, gravida, consanguinity, maternal age at delivery, and neonatal sex were determined to be the six most important variables associated with LBW. Our findings underscore the importance of facilitating timely diagnosis of causes of abortion, providing genetic counseling to consanguineous couples, and strengthening care before and during pregnancy (particularly for young mothers) to reduce LBW.

Associations of green and blue space exposure in pregnancy with epigenetic gestational age acceleration

ABSTRACT Early life is seen as a particularly sensitive period for environmental exposures. Natural space exposure during pregnancy has been associated with offspring health. Epigenetic gestational age acceleration, a discrepancy between clinical and DNA methylation-based gestational age, may underlie these associations. In 1359 mother-newborn pairs from the population-based Generation R Study, we examined the associations of natural space exposure, defined as surrounding greenness, distance to major green and blue (water) space, and size of the blue space during pregnancy with offspring epigenetic gestational age acceleration. Natural space exposure was based on participants’ geocoded addresses, and epigenetic gestational age acceleration was calculated from cord blood DNA methylation using Bohlin’s and Knight’s epigenetic clocks. Sensitivity analyses were conducted in a subgroup of newborns with optimal pregnancy dating, based on last menstrual period. Surrounding greenness, measured in normalized difference vegetation index values, was intermediate (median 0.4, IQR 0.2), and 84% and 56% of the participants had a major green or blue space near their home address, respectively. We did not observe associations of natural space availability during pregnancy with offspring epigenetic gestational age acceleration. This could imply that epigenetic gestational age acceleration in cord blood does not underlie the effects of residential natural space availability in pregnancy on offspring health. Future studies could investigate whether residential natural space availability during pregnancy is associated with offspring differential DNA methylation at other CpGs than those included in the epigenetic gestational clocks.

Association between rare earth element exposure during pregnancy and newborn telomere length.

Telomere length (TL) is considered a marker of biological aging and lifetime health, and some epidemiological studies report that the environmental exposures may influence TL at birth. We aimed to investigate the associations between prenatal rare earth elements (REE) exposure and newborn TL. A total of 587 mother-newborn pairs were recruited during 2013 to 2015 in Wuhan, China. Maternal urinary concentrations of REE collected during three trimesters were measured by inductively coupled plasma mass spectrometry. Quantitative real-time polymerase chain reaction was used to measure relative cord blood TL. The trimester-specific associations between prenatal REE exposure and cord blood TL were evaluated using multiple informant models. Weighted quantile sum regression was used to estimate the mixture effect of urinary REE on cord blood TL. After adjustment for potential confounders, per doubling of urinary REE (Dy, Yb, Pr, Nd, and Tm) concentrations (μg/g creatinine) during the second trimester was respectively associated with 1.94% (95% CI 0.19%, 3.72%), 2.10% (95% CI 0.31%, 3.92%), 2.11% (95% CI 0.35%, 3.89%), 2.08% (95% CI 0.01%, 4.20%), and 1.38% (95% CI 0.09%, 2.70%) increase in cord blood TL. Furthermore, exposure to the mixture of REE during the second trimester was also significantly associated with increased cord blood TL (percent change 1.20%, 95% CI 0.30%, 2.11%). However, these associations were not statistically significant in the first and third trimesters. This study provides new evidence on the potential effect of prenatal REE exposure on the initial (newborn) setting of offspring's telomere biology. Further epidemiological studies are warranted to confirm our findings.

The association between ambient particulate matter exposure and the telomere–mitochondrial axis of aging in newborns

BackgroundParticulate matter (PM) is associated with aging markers at birth, including telomeres and mitochondria. It is unclear whether markers of the core-axis of aging, i.e. tumor suppressor p53 (p53) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), are associated with prenatal air pollution and whether there are underlying mechanisms. Methods556 mother-newborn pairs from the ENVIRONAGE birth cohort were recruited at the East Limburg Hospital in Genk (Belgium). In placenta and cord blood, telomere length (TL) and mitochondrial DNA content (mtDNAc) were measured using quantitative real-time polymerase chain reaction (qPCR). In cord plasma, p53 and PGC-1α protein levels were measured using ELISA. Daily ambient PM2.5 concentrations during gestation were calculated using a spatial temporal interpolation model. Distributed lag models (DLMs) were applied to assess the association between prenatal PM2.5 exposure and each molecular marker. Mediation analysis was performed to test for underlying mechanisms. ResultsA 5 µg/m3 increment in PM2.5 exposure was associated with −11.23 % (95 % CI: −17.36 % to −4.65 %, p = 0.0012) and −7.34 % (95 % CI: −11.56 % to −2.92 %, p = 0.0014) lower placental TL during the entire pregnancy and second trimester respectively, and with −12.96 % (95 % CI: −18.84 % to −6.64 %, p < 0.001) lower placental mtDNAc during the third trimester. Furthermore, PM2.5 exposure was associated with a 12.42 % (95 % CI: −1.07 % to 27.74 %, p = 0.059) higher cord plasma p53 protein level and a −3.69 % (95 % CI: −6.97 % to −0.31 %, p = 0.033) lower cord plasma PGC-1α protein level during the third trimester. Placental TL mediated 65 % of the negative and 17 % of the positive association between PM2.5 and placental mtDNAc and cord plasma p53 protein levels, respectively. ConclusionAmbient PM2.5 exposure during pregnancy is associated with markers of the core-axis of aging, with TL as a mediating factor. This study strengthens the hypothesis of the air pollution induced core-axis of aging, and may unravel a possible underlying mediating mechanism in an early-life epidemiological context.

In Utero Exposure to Air Pollutants and Mitochondrial Heteroplasmy in Neonates.

Mitochondria are sensitive to oxidative stress, which can be caused by traffic-related air pollution. Placental mitochondrial DNA (mtDNA) mutations have been previously linked with air pollution. However, the relationship between prenatal air pollution and cord-blood mtDNA mutations has been poorly understood. Therefore, we hypothesized that prenatal particulate matter (PM2.5) and NO2 exposures are associated with cord-blood mtDNA heteroplasmy. As part of the ENVIRONAGE cohort, 200 mother-newborn pairs were recruited. Cord-blood mitochondrial single-nucleotide polymorphisms were identified by whole mitochondrial genome sequencing, and heteroplasmy levels were evaluated based on the variant allele frequency (VAF). Outdoor PM2.5 and NO2 concentrations were determined by a high-resolution spatial-temporal interpolation method based on the maternal residential address. Distributed lag linear models were used to determine sensitive time windows for the association between NO2 exposure and cord-blood mtDNA heteroplasmy. A 5 μg/m3 increment in NO2 was linked with MT-D-Loop16311T>C heteroplasmy from gestational weeks 17-25. MT-CYTB14766C>T was negatively associated with NO2 exposure in mid pregnancy, from weeks 14-17, and positively associated in late pregnancy, from weeks 31-36. No significant associations were observed with prenatal PM2.5 exposure. This is the first study to show that prenatal NO2 exposure is associated with cord-blood mitochondrial mutations and suggests two critical windows of exposure in mid-to-late pregnancy.

DETECCIÓN CLONAL DE CEPAS PARENTALES DE Streptococcus agalactiae Lehmann y Neumann POR AMPLIFICACIÓN ALEATORIA DE ADN POLIMÓRFICO

Streptococcus agalactiae (GBS) causes invasive infections in newborns, being the most frequent the maternal transmission. Epidemiological studies use molecular techniques that assess genetic diversity, including random amplification of polymorphic DNA (RAPD) that is found to be accessible, sensitive and uses arbitrary primers to amplify polymorphic segments of DNA by PCR. The objective was to determine the clonal relationship between GBS strains recovered from mothers and their respective newborns. Four pairs of GBS isolates obtained from vaginal-rectal swabs of mothers and blood cultures of their newborns were studied with RAPD. Primers OPS11, OPB17 and OPB18 were used to select one with the ability to discriminate between non-genetically related strains. The Hunter-Gaston formula that establishes the discrimination index (D) was used; when D&gt;0.90, it is considered that the isolates belong to different clones. The amplification profiles for the eight isolates, using each primer independently, allowed to calculate a D=1 for OPS11, and D=0.84 for OPB17 and OPB18. Therefore, OPS11 was selected for the study of the clonal relationship of the isolates, and similar amplification profiles were found by RAPD for each mother-newborn pair of GBS isolates. Different amplification profiles were observed between pairs of mother-newborn strains, which reveals the discrimination between unrelated strains, confirmed by pulsating field electrophoresis (PFGE). These results indicated vertical transmission for each studied case and robustness of the OPS11 primer. Appropriate conditions of the RAPD trial were found, which is useful for epidemiological studies. Key words: Streptococcus agalactiae, neonatal disease, molecular epidemiology, RAPD technique, vertical transmission