Browsing by Subject "Gestational Age"
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Item Open Access Antenatal haemoglobin A1c and risk of large-for-gestational-age infants in a multi-ethnic cohort of women with gestational diabetes.(Paediatric and perinatal epidemiology, 2012-05) Katon, Jodie; Reiber, Gayle; Williams, Michelle A; Yanez, David; Miller, EdithGestational diabetes mellitus (GDM) is a risk factor for delivering a large-for-gestational-age (LGA) infant. Haemoglobin A1c (A1C) is an indicator of glycaemic control. The objective of this study was to test whether higher A1C quartile at the time of diagnosis of GDM is associated with increased risk of delivering a LGA or macrosomic infant. Women with singleton pregnancies treated for GDM at a large diabetes and pregnancy programme located in Charlotte, North Carolina, were eligible for inclusion in this retrospective cohort study. Clinical information, including A1C at diagnosis, treatment, prior medical and obstetric history, and birth data were abstracted from medical records. LGA was defined as birthweight >90th percentile for gestational age and sex and macrosomia as birthweight >4000 g. Logistic regression was used to analyse the association of A1C at GDM diagnosis with risk of delivering LGA or macrosomic infants. This study included 502 women. Prevalences of LGA and macrosomia were 4% and 6% respectively. After adjustment there was no detectable trend of increased risk for LGA (P for trend = 0.12) or macrosomia (P for trend = 0.20) across increasing quartiles of A1C at GDM diagnosis. A1C at GDM diagnosis may not be linearly associated with LGA or macrosomia, possibly because of the mediating effect of strict glycaemic control in this clinical setting.Item Open Access Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis.(The American journal of clinical nutrition, 2024-01) Monangi, Nagendra K; Xu, Huan; Fan, Yue-Mei; Khanam, Rasheeda; Khan, Waqasuddin; Deb, Saikat; Pervin, Jesmin; Price, Joan T; Kaur, Lovejeet; INTERBIO-21st Study Consortium; Al Mahmud, Abdullah; Thanh, Le Quang; Care, Angharad; Landero, Julio A; Combs, Gerald F; Belling, Elizabeth; Chappell, Joanne; Chen, Jing; Kong, Fansheng; Lacher, Craig; Ahmed, Salahuddin; Chowdhury, Nabidul Haque; Rahman, Sayedur; Kabir, Furqan; Nisar, Imran; Hotwani, Aneeta; Mehmood, Usma; Nizar, Ambreen; Khalid, Javairia; Dhingra, Usha; Dutta, Arup; Ali, Said Mohamed; Aftab, Fahad; Juma, Mohammed Hamad; Rahman, Monjur; Ahmed, Tahmeed; Islam, M Munirul; Vwalika, Bellington; Musonda, Patrick; Ashorn, Ulla; Maleta, Kenneth; Hallman, Mikko; Goodfellow, Laura; Gupta, Juhi K; Alfirevic, Ana; Murphy, Susan K; Rand, Larry; Ryckman, Kelli K; Murray, Jeffrey C; Bahl, Rajiv; Litch, James A; Baruch-Gravett, Courtney; Sopory, Shailaja; Chandra Mouli Natchu, Uma; Kumar, Pavitra V; Kumari, Neha; Thiruvengadam, Ramachandran; Singh, Atul Kumar; Kumar, Pankaj; GARBH-Ini study team; Alfirevic, Zarko; Baqui, Abdullah H; Bhatnagar, Shinjini; Hirst, Jane E; Hoyo, Cathrine; Jehan, Fyezah; Jelliffe-Pawlowski, Laura; Rahman, Anisur; Roth, Daniel E; Sazawal, Sunil; Stringer, Jeffrey SA; Ashorn, Per; Zhang, Ge; Muglia, Louis JBackground
Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB).Objectives
This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations.Methods
Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort.Results
The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 μg/mL and standard deviation of 0.43 μg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 μg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration.Conclusions
Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.Item Open Access Bacteria localization and chorion thinning among preterm premature rupture of membranes.(PLoS One, 2014) Murtha, AP; Fortner, KB; Grotegut, CA; Ransom, CE; Bentley, RC; Feng, L; Lan, L; Heine, RP; Seed, PCOBJECTIVE: Bacterial colonization of the fetal membranes and its role in pathogenesis of membrane rupture is poorly understood. Prior retrospective work revealed chorion layer thinning in preterm premature rupture of membranes (PPROM) subjects. Our objective was to prospectively examine fetal membrane chorion thinning and to correlate to bacterial presence in PPROM, preterm, and term subjects. STUDY DESIGN: Paired membrane samples (membrane rupture and membrane distant) were prospectively collected from: PPROM = 14, preterm labor (PTL = 8), preterm no labor (PTNL = 8), term labor (TL = 10), and term no labor (TNL = 8), subjects. Sections were probed with cytokeratin to identify fetal trophoblast layer of the chorion using immunohistochemistry. Fluorescence in situ hybridization was performed using broad range 16 s ribosomal RNA probe. Images were evaluated, chorion and choriodecidua were measured, and bacterial fluorescence scored. Chorion thinning and bacterial presence were compared among and between groups using Student's t-test, linear mixed effect model, and Poisson regression model (SAS Cary, NC). RESULTS: In all groups, the fetal chorion cellular layer was thinner at rupture compared to distant site (147.2 vs. 253.7 µm, p<0.0001). Further, chorion thinning was greatest among PPROM subjects compared to all other groups combined, regardless of site sampled [PPROM(114.9) vs. PTL(246.0) vs. PTNL(200.8) vs. TL(217.9) vs. TNL(246.5)]. Bacteria counts were highest among PPROM subjects compared to all other groups regardless of site sampled or histologic infection [PPROM(31) vs. PTL(9) vs. PTNL(7) vs. TL(7) vs. TNL(6)]. Among all subjects at both sites, bacterial counts were inversely correlated with chorion thinning, even excluding histologic chorioamnionitis (p<0.0001 and p = 0.05). CONCLUSIONS: Fetal chorion was uniformly thinner at rupture site compared to distant sites. In PPROM fetal chorion, we demonstrated pronounced global thinning. Although cause or consequence is uncertain, bacterial presence is greatest and inversely correlated with chorion thinning among PPROM subjects.Item Open Access Cognitive and Behavioral Impairments Evoked by Low-Level Exposure to Tobacco Smoke Components: Comparison with Nicotine Alone.(Toxicological sciences : an official journal of the Society of Toxicology, 2016-06) Hall, Brandon J; Cauley, Marty; Burke, Dennis A; Kiany, Abtin; Slotkin, Theodore A; Levin, Edward DActive maternal smoking has adverse effects on neurobehavioral development of the offspring, with nicotine (Nic) providing much of the underlying causative mechanism. To determine whether the lower exposures caused by second-hand smoke are deleterious, we administered tobacco smoke extract (TSE) to pregnant rats starting preconception and continued through the second postnatal week, corresponding to all 3 trimesters of fetal brain development. Dosing was adjusted to produce maternal plasma Nic concentrations encountered with second-hand smoke, an order of magnitude below those seen in active smokers. We then compared TSE effects to those of an equivalent dose of Nic alone, and to a 10-fold higher Nic dose. Gestational exposure to TSE and Nic significantly disrupted cognitive and behavioral function in behavioral tests given during adolescence and adulthood (postnatal weeks 4-40), producing hyperactivity, working memory deficits, and impairments in emotional processing, even at the low exposure levels corresponding to second-hand smoke. Although TSE effects were highly correlated with those of Nic, the effects of TSE were much larger than could be attributed to just the Nic in the mixture. Indeed, TSE effects more closely resembled those of the 10-fold higher Nic levels, but still exceeded their magnitude. In combination with our earlier findings, this study thus completes the chain of causation to prove that second-hand smoke exposure causes neurodevelopmental deficits, originating in disruption of neurodifferentiation, leading to miswiring of neuronal circuits, and as shown here, culminating in behavioral dysfunction. As low level exposure to Nic alone produced neurobehavioral teratology, 'harm reduction' Nic products do not abolish the potential for neurodevelopmental damage.Item Open Access Folic acid supplementation before and during pregnancy in the Newborn Epigenetics STudy (NEST).(BMC public health, 2011-01-21) Hoyo, Cathrine; Murtha, Amy P; Schildkraut, Joellen M; Forman, Michele R; Calingaert, Brian; Demark-Wahnefried, Wendy; Kurtzberg, Joanne; Jirtle, Randy L; Murphy, Susan KBackground
Folic acid (FA) added to foods during fortification is 70-85% bioavailable compared to 50% of folate occurring naturally in foods. Thus, if FA supplements also are taken during pregnancy, both mother and fetus can be exposed to FA exceeding the Institute of Medicine's recommended tolerable upper limit (TUL) of 1,000 micrograms per day (μg/d) for adult pregnant women. The primary objective is to estimate the proportion of women taking folic acid (FA) doses exceeding the TUL before and during pregnancy, and to identify correlates of high FA use.Methods
During 2005-2008, pre-pregnancy and pregnancy-related data on dietary supplementation were obtained by interviewing 539 pregnant women enrolled at two obstetrics-care facilities in Durham County, North Carolina.Results
Before pregnancy, 51% of women reported FA supplementation and 66% reported this supplementation during pregnancy. Before pregnancy, 11.9% (95% CI = 9.2%-14.6%) of women reported supplementation with FA doses above the TUL of 1,000 μg/day, and a similar proportion reported this intake prenatally. Before pregnancy, Caucasian women were more likely to take FA doses above the TUL (OR = 2.99; 95% = 1.28-7.00), compared to African American women, while women with chronic conditions were less likely to take FA doses above the TUL (OR = 0.48; 95%CI = 0.21-0.97). Compared to African American women, Caucasian women were also more likely to report FA intake in doses exceeding the TUL during pregnancy (OR = 5.09; 95%CI = 2.07-12.49).Conclusions
Fifty-one percent of women reported some FA intake before and 66% during pregnancy, respectively, and more than one in ten women took FA supplements in doses that exceeded the TUL. Caucasian women were more likely to report high FA intake. A study is ongoing to identify possible genetic and non-genotoxic effects of these high doses.Item Open Access Gestational age modifies the association between exposure to fine particles and fetal death: findings from a nationwide epidemiological study in the contiguous United States.(Environmental health : a global access science source, 2023-09) Tong, Mingkun; Lin, Weiwei; Liu, Hengyi; Gong, Jicheng; Zhang, Junfeng Jim; Xue, TaoBackgrounds
The vulnerability of fetuses differs at different developmental stages, in response to environmental stressors such as fine particulate matter (PM2.5), a ubiquitous air pollutant. Whether gestational age (GA) modifies the association between prenatal fine particulate matter (PM2.5) exposure and fetal death remains unclear.Methods
We selected approximately 47.8 million eligible United States (US) livebirth and fetal death (defined as a termination at a GA of 20-43 weeks) records from 1989 to 2004. For each record, we took the level of prenatal exposure to PM2.5 as the average concentration in the mother's residential county during the entire gestational period, or a specific trimester (i.e., GA-specific exposure), according to well-established estimates of monthly levels across the contiguous US. First, we evaluated the associations between PM2.5 exposure and fetal death at a specific GA (i.e., GA-specific outcome) using five different logit models (unadjusted, covariate-adjusted, propensity-score, double robust, and diagnostic-score models). Double robust model was selected as the main model due to its advantages in causal inference. Then, we conducted meta-analyses to pool the estimated GA-specific associations, and explored how the pooled estimates varied with GA.Results
According to the meta-analysis, all models suggested gestational PM2.5 exposure was associated with fetal death. However, there was slight heterogeneity in the estimated effects, as different models revealed a range of 3.6-10.7% increase in the odds of fetal death per 5-µg/m3 increment of PM2.5. Each 5-µg/m3 increase in PM2.5 exposure during the entire gestation period significantly increased the odds of fetal death, by 8.1% (95% confidence interval [CI]: 5.1-11.2%). In terms of GA-specific outcomes, the odds of fetal death at a GA of 20-27, 28-36, or ≥ 37 weeks increased by 11.0% (5.9-16.4%), 5.2% (0.4-10.1%), and 8.3% (2.5-14.5%), respectively. In terms of GA-specific exposure, the odds of fetal death increased by 6.0% (3.9-8.2%), 4.1% (3.9-8.2%), and 4.3% (0.5-8.2%) with 5-µg/m3 increases in PM2.5 exposure during the first, second, and third trimester, respectively. The association had the largest effect size (odds ratio = 1.098, 95% CI: 1.061-1.137) between PM2.5 exposure during early gestation (i.e., first trimester) and early fetal death (i.e., 20-27 weeks).Conclusions
Prenatal exposure to PM2.5 was significantly associated with an increased risk of fetal death. The association was varied by gestational-age-specific exposures or outcomes, suggesting gestation age as a potential modifier on the effect of PM2.5. The fetus was most vulnerable during the early stage of development to death associated with PM2.5 exposure.Item Open Access Gestational Stage and IFN-λ Signaling Regulate ZIKV Infection In Utero.(Cell host & microbe, 2017-09) Jagger, Brett W; Miner, Jonathan J; Cao, Bin; Arora, Nitin; Smith, Amber M; Kovacs, Attila; Mysorekar, Indira U; Coyne, Carolyn B; Diamond, Michael SAlthough Zika virus (ZIKV)-induced congenital disease occurs more frequently during early stages of pregnancy, its basis remains undefined. Using established type I interferon (IFN)-deficient mouse models of ZIKV transmission in utero, we found that the placenta and fetus were more susceptible to ZIKV infection at earlier gestational stages. Whereas ZIKV infection at embryonic day 6 (E6) resulted in placental insufficiency and fetal demise, infections at midstage (E9) resulted in reduced cranial dimensions, and infection later in pregnancy (E12) caused no apparent fetal disease. In addition, we found that fetuses lacking type III IFN-λ signaling had increased ZIKV replication in the placenta and fetus when infected at E12, and reciprocally, treatment of pregnant mice with IFN-λ2 reduced ZIKV infection. IFN-λ treatment analogously diminished ZIKV infection in human midgestation fetal- and maternal-derived tissue explants. Our data establish a model of gestational stage dependence of ZIKV pathogenesis and IFN-λ-mediated immunity at the maternal-fetal interface.Item Open Access In-hospital outcomes of premature infants with severe bronchopulmonary dysplasia.(Journal of perinatology : official journal of the California Perinatal Association, 2017-07) Jackson, W; Hornik, CP; Messina, JA; Guglielmo, K; Watwe, A; Delancy, G; Valdez, A; MacArthur, T; Peter-Wohl, S; Smith, PB; Tolia, VN; Laughon, MMOBJECTIVE:To characterize in-hospital outcomes of premature infants diagnosed with severe bronchopulmonary dysplasia (BPD). STUDY DESIGN:Retrospective cohort study including premature infants with severe BPD discharged from 348 Pediatrix Medical Group neonatal intensive care units from 1997 to 2015. RESULTS:There were 10 752 infants with severe BPD, and 549/10 752 (5%) died before discharge. Infants who died were more likely to be male, small for gestational age, have received more medical interventions and more frequently diagnosed with surgical necrotizing enterocolitis, culture-proven sepsis and pulmonary hypertension following 36 weeks of postmenstrual age compared with survivors. Approximately 70% of infants with severe BPD were discharged by 44 weeks of postmenstrual age, and 86% were discharged by 48 weeks of postmenstrual age. CONCLUSIONS:A majority of infants diagnosed with severe BPD were discharged home by 44 weeks of postmenstrual age. These results may inform discussions with families regarding the expected hospital course of infants diagnosed with severe BPD.Item Open Access Maternal Exposure to Per- and Polyfluorinated alkyl substances (PFAS) in Drinking Water and Associations with Birth Outcomes(2020-04-24) Xiong, WanchenPer- and polyfluoroalkyl substances (PFAS), used in firefighting foam and as water and oil-repellants in nonstick cookware, fabrics and other materials, are widely detected in watersheds across the United States, and globally. Epidemiological studies have found that PFAS are associated with adverse health effects, including thyroid disease, cancer, and adverse birth outcomes. In 2017-2018, high levels of PFAS were detected in both the Haw River and Cape Fear River in North Carolina, raising concerns for potential health effects in towns which draw drinking water from these rivers. This research sought to examine associations between exposure to PFAS (using watershed as a proxy for PFAS exposure) and birth outcomes in NC, focusing specifically on birth weight and gestational age at birth. A multiple linear regression model was used to compare outcomes in eleven regions of NC, defined by their drinking water source. After adjusting for potential confounders and stratifying analyses by infant sex, the largest difference in birth weight was observed in the Headwater of the Cape Fear River (serving the population of Eastern Chatham County and Goldston-Gulf District), where male infants were born 0.26 lbs (± 0.13) lighter on average, and were born 4.72 (± 1.93) days earlier, than the reference group (Falls Lake (Raleigh); p<0.1 for birth weight and p<0.05 for gestational age). Similar patterns were observed in populations drawing water from Lake Mackintosh, Jordan Lake, and the Cape Fear River, whereas no statistically significant differences in birth weight or gestational age were observed in the population drawing water from the Haw River (i.e., the Town of Pittsboro). Overall, the research study concluded that there are spatial differences in adverse birth outcomes across NC, which may be due to exposure to contaminants in water such as PFAS; however, future studies are needed to specially examine PFAS exposures at the individual level.Item Open Access Optimizing donor selection for public cord blood banking: influence of maternal, infant, and collection characteristics on cord blood unit quality.(Transfusion, 2014-02) Page, Kristin M; Mendizabal, Adam; Betz-Stablein, Brigid; Wease, Stephen; Shoulars, Kevin; Gentry, Tracy; Prasad, Vinod K; Sun, Jessica; Carter, Shelly; Balber, Andrew E; Kurtzberg, JoanneBackground
Banked unrelated donor umbilical cord blood (CB) has improved access to hematopoietic stem cell transplantation for patients without a suitably matched donor. In a resource-limited environment, ensuring that the public inventory is enriched with high-quality cord blood units (CBUs) addressing the needs of a diverse group of patients is a priority. Identification of donor characteristics correlating with higher CBU quality could guide operational strategies to increase the yield of banked high-quality CBUs.Study design and methods
Characteristics of 5267 CBUs donated to the Carolinas Cord Blood Bank, a public bank participating in the National Cord Blood Inventory, were retrospectively analyzed. Eligible CBUs, collected by trained personnel, were processed using standard procedures. Routine quality and potency metrics (postprocessing total nucleated cell count [post-TNCC], CD34+, colony-forming units [CFUs]) were correlated with maternal, infant, and collection characteristics.Results
High-quality CBUs were defined as those with higher post-TNCC (>1.25 × 10(9)) with CD34+ and CFUs in the upper quartile. Factors associated with higher CD34+ or CFU content included a shorter interval from collection to processing (<10 hr), younger gestational age (34-37 weeks; CD34+ and CFUs), Caucasian race, higher birthweight (>3500 g), and larger collection volumes (>80 mL).Conclusions
We describe characteristics identifying high-quality CBUs, which can be used to inform strategies for CBU collection for public banks. Efforts should be made to prioritize collections from larger babies born before 38 weeks of gestation. CBUs should be rapidly transported to the processing laboratory. The lower quality of CBUs from non-Caucasian donors highlights the challenges of building a racially diverse public CB inventory.Item Open Access Ratios of head circumference to ventricular size vary over time and predict eventual need for CSF diversion in intraventricular hemorrhage of prematurity.(Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2024-03) Venkatraman, Vishal; Harward, Stephen C; Bhasin, Srijan; Calderon, Kylie; Atkins, Sage L; Liu, Beiyu; Lee, Hui-Jie; Chow, Shein-Chung; Fuchs, Herbert E; Thompson, Eric MPurpose
Intraventricular hemorrhage (IVH) of prematurity can lead to hydrocephalus, sometimes necessitating permanent cerebrospinal fluid (CSF) diversion. We sought to characterize the relationship between head circumference (HC) and ventricular size in IVH over time to evaluate the clinical utility of serial HC measurements as a metric in determining the need for CSF diversion.Methods
We included preterm infants with IVH born between January 2000 and May 2020. Three measures of ventricular size were obtained: ventricular index (VI), Evan's ratio (ER), and frontal occipital head ratio (FOHR). The Pearson correlations (r) between the initial (at birth) paired measurements of HC and ventricular size were reported. Multivariable longitudinal regression models were fit to examine the HC:ventricle size ratio, adjusting for the age of the infant, IVH grade (I/II vs. III/IV), need for CSF diversion, and sex.Results
A total of 639 patients with an average gestational age of 27.5 weeks were included. IVH grade I/II and grade III/IV patients had a positive correlation between initial HC and VI (r = 0.47, p < 0.001 and r = 0.48, p < 0.001, respectively). In our longitudinal models, patients with a low-grade IVH (I/II) had an HC:VI ratio 0.52 higher than those with a high-grade IVH (p-value < 0.001). Patients with low-grade IVH had an HC:ER ratio 12.94 higher than those with high-grade IVH (p-value < 0.001). Patients with low-grade IVH had a HC:FOHR ratio 12.91 higher than those with high-grade IVH (p-value < 0.001). Infants who did not require CSF diversion had an HC:VI ratio 0.47 higher than those who eventually did (p < 0.001). Infants without CSF diversion had an HC:ER ratio 16.53 higher than those who received CSF diversion (p < 0.001). Infants without CSF diversion had an HC:FOHR ratio 15.45 higher than those who received CSF diversion (95% CI (11.34, 19.56), p < 0.001).Conclusions
There is a significant difference in the ratio of HC:VI, HC:ER, and HC:FOHR size between patients with high-grade IVH and low-grade IVH. Likewise, there is a significant difference in HC:VI, HC:ER, and HC:FOHR between those who did and did not have CSF diversion. The routine assessments of both head circumference and ventricle size by ultrasound are important clinical tools in infants with IVH of prematurity.