Browsing by Subject "Preterm birth"

Now showing 1 - 10 of 14
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    Association of Adverse Pregnancy Outcomes With Hypertension 2 to 7 Years Postpartum
    (Wiley Open Access, 2019-10-01) Haas, David M.; Parker, Corette B.; Marsh, Derek J.; Grobman, William A.; Ehrenthal, Deborah B.; Greenland, Philip; Merz, C. Noel Bairey; Pemberton, Victoria L.; Silver, Robert M.; Barnes, Shannon; McNeil, Rebecca B.; Cleary, Kirsten; Reddy, Uma M.; Chung, Judith H.; Parry, Samuel; Theilen, Lauren H.; Blumenthal, Elizabeth A.; Levine, Lisa D.; Mercer, Brian M.; Simhan, Hyagriv; Polito, LuAnn; Wapner, Ronald J.; Catov, Janet; Chen, Ida; Saade, George R. Saade; NHLBI nuMoM2b Heart Health Study; Medicine, School of Medicine
    Background Identifying pregnancy-associated risk factors before the development of major cardiovascular disease events could provide opportunities for prevention. The objective of this study was to determine the association between outcomes in first pregnancies and subsequent cardiovascular health. Methods and Results The Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be Heart Health Study is a prospective observational cohort that followed 4484 women 2 to 7 years (mean 3.2 years) after their first pregnancy. Adverse pregnancy outcomes (defined as hypertensive disorders of pregnancy, small-for-gestational-age birth, preterm birth, and stillbirth) were identified prospectively in 1017 of the women (22.7%) during this pregnancy. The primary outcome was incident hypertension (HTN). Women without adverse pregnancy outcomes served as controls. Risk ratios (RR) and 95% CIs were adjusted for age, smoking, body mass index, insurance type, and race/ethnicity at enrollment during pregnancy. The overall incidence of HTN was 5.4% (95% CI 4.7% to 6.1%). Women with adverse pregnancy outcomes had higher adjusted risk of HTN at follow-up compared with controls (RR 2.4, 95% CI 1.8-3.1). The association held for individual adverse pregnancy outcomes: any hypertensive disorders of pregnancy (RR 2.7, 95% CI 2.0-3.6), preeclampsia (RR 2.8, 95% CI 2.0-4.0), and preterm birth (RR 2.7, 95% CI 1.9-3.8). Women who had an indicated preterm birth and hypertensive disorders of pregnancy had the highest risk of HTN (RR 4.3, 95% CI 2.7-6.7). Conclusions Several pregnancy complications in the first pregnancy are associated with development of HTN 2 to 7 years later. Preventive care for women should include a detailed pregnancy history to aid in counseling about HTN risk.
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    Corrigendum to The impact of risk factors on aspirin's efficacy for the prevention of preterm birth. American Journal of Obstetrics & Gynecology MFM. Volume 5, Issue 10, October 2023, 101095
    (Elsevier, 2024) Nuss, Emily E.; Hoffman, Matthew K.; Goudar, Shivaprasad S.; Kavi, Avinash; Metgud, Mrityunjay; Somannavar, Manjunath; Okitawutshu, Jean; Lokangaka, Adrien; Tshefu, Antoinette; Bauserman, Melissa; Tembo, Abigail Mwapule; Chomba, Elwyn; Carlo, Waldemar A.; Figueroa, Lester; Krebs, Nancy F.; Jessani, Saleem; Saleem, Sarah; Goldenberg, Robert L.; Kurhe, Kunal; Das, Prabir; Hibberd, Patricia L.; Achieng, Emmah; Nyongesa, Paul; Esamai, Fabian; Liechty, Edward A.; Bucher, Sherri; Goco, Norman; Hemingway-Foday, Jennifer; Moore, Janet; McClure, Elizabeth M.; Silver, Robert M.; Derman, Richard J.; Patel, Archana; Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas Study Group; Pediatrics, School of Medicine
    The authors regret that the originally published manuscript erroneously excluded a contributing author Archana Patel MD, PhD. The authors would like to apologise for any inconvenience caused.
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    Dietary Fat and Fatty Acid Intake in Nulliparous Women: Associations with Preterm Birth and Distinctions by Maternal BMI
    (Oxford University Press, 2021-05-08) Robinson, Daniel T.; Van Horn, Linda; Balmert, Lauren; Silver, Robert M.; Parry, Samuel; Haas, David M.; Wing, Deborah A.; Grobman, William A.; Obstetrics and Gynecology, School of Medicine
    Background: Evidence documenting whether diet quality, particularly dietary fatty acids, is associated with preterm birth (PTB) is limited. Objective: The aim was to measure associations between dietary fatty acid intake prior to pregnancy, specifically n-3 (ɷ-3) PUFAs and odds of PTB in US women and determine if associations differed by prepregnancy BMI. Methods: We designed a secondary analysis of dietary intake in nulliparous women enrolled in a longitudinal cohort (NCT01322529). Participants completed an FFQ, modified to assess detailed PUFA intake, during the 3 mo preceding pregnancy. Inclusion in this analytic cohort required total energy intake within 2 SDs of the group mean. Prepregnancy BMI was categorized as underweight, normal, overweight, or obese. The primary exposure was estimated intake of EPA and DHA (combined EPA+DHA), in the context of a recommended intake of 250 mg. The primary outcome was PTB (<37 wk). Adjusted regression models controlled for maternal factors relevant to PTB and evaluated associations with PUFAs. Interaction terms estimated effect modification of BMI. A false discovery rate (FDR) correction accounted for multiple comparisons. Results: Median daily intake of combined EPA+DHA in 7365 women was 70 mg (IQR: 32, 145 mg). A significant interaction term indicated the effects of EPA+DHA on odds of PTB were different for different BMI categories (P < 0.01). Specifically, higher intake of combined EPA+DHA was nominally associated with reduced odds of PTB in women with underweight (OR: 0.67; 95% CI: 0.46-0.98) and normal BMI (OR: 0.87; 95% CI: 0.78-0.96), yet was associated with increased odds of overweight BMI (OR: 1.21; 95% CI: 1.02-1.44). Associations remained significant after FDR correction. Conclusions: Based on a cohort of US women designed to identify predictors of adverse pregnancy outcomes, dietary intake of combined EPA+DHA was considerably lower than recommended. Associations between intake of these recommended n-3 fatty acids and risk of PTB differ by maternal BMI.
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    Do maternal demographics and prenatal history impact the efficacy of betamethasone therapy for threatened preterm labor?
    (BMC, 2021-06-24) Kinney, Mary T.; Quinney, Sara K.; Trussell, Hayley K.; Silva, Larissa L.; Ibrahim, Sherrine A.; Haas, David M.; Obstetrics and Gynecology, School of Medicine
    Background: Betamethasone (BMZ) is used to accelerate fetal lung maturation in women with threatened preterm birth, but its efficacy is variable and limited by the lack of patient individualization in its dosing and administration. To determine sources of variability and potential opportunities for individualization of therapy, the objective of this study was to evaluate maternal factors associated with development of neonatal respiratory distress syndrome (RDS) in a cohort of women who received betamethasone. Methods: This study prospectively enrolled women, gestational ages 23-34 weeks, who received betamethasone for threatened preterm birth. Maternal demographics, prenatal history, and neonatal outcomes were abstracted from hospital records. RDS was the primary outcome. Associations between RDS diagnosis and maternal demographics, prenatal history, and betamethasone dosing were evaluated in a case-control analysis and multivariable regression adjusted for gestational age at delivery. Secondary analyses limited the cohort to women who delivered within 1 or 2 weeks of betamethasone dosing. Results: Of 209 deliveries, 90 (43 %) resulted in neonatal RDS. Within the overall cohort and controlling for gestational age at birth, RDS was only associated with cesarean births compared to vaginal births (adjusted OR 1.17 [1.06-1.29]). Route of delivery was also the only significant factor related to RDS in the 83 neonates delivered within 7 days of BMZ dosing. However, among 101 deliveries within 14 days of betamethasone dosing and controlling for gestational age at birth, women who experienced preterm premature rupture of membranes (PPROM) had lower RDS rates than those without PPROM (57.9 % vs. 80.2 %, adjusted OR 0.81 [0.67-0.99]). Maternal age, BMI, race, and ethnicity were not associated with RDS in the regression models. Conclusions: Of maternal characteristics analyzed, only delivery by cesarean was associated with neonatal RDS after antenatal betamethasone use.
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    Epigenetic biomarker for preeclampsia-associated preterm birth and potential preventative medicine
    (Oxford University Press, 2024-11-06) Nilsson, Eric E.; Winchester, Paul; Proctor, Cathy; Beck, Daniel; Skinner, Michael K.; Pediatrics, School of Medicine
    Preterm birth (PTB) has dramatically increased within the population (i.e. >10%) and preeclampsia is a significant sub-category of PTB. Currently, there are no practical clinical parameters or biomarkers which predict preeclampsia induced PTB. The current study investigates the potential use of epigenetic (DNA methylation) alterations as a maternal preeclampsia biomarker. Non-preeclampsia term births were compared to preeclampsia PTBs to identify DNA methylation differences (i.e. potential epigenetic biomarker). Maternal buccal cell cheek swabs were used as a marker cell for systemic epigenetic alterations in the individuals, which are primarily due to environmentally induced early life or previous generations impacts, and minimally impacted or associated with the disease etiology or gestation variables. A total of 389 differential DNA methylation regions (DMRs) were identified and associated with the presence of preeclampsia. The DMRs were genome-wide and were predominantly low CpG density (<2 CpG/100 bp). In comparison with a previous PTB buccal cell epigenetic biomarker there was a 15% (60 DMR) overlap, indicating that the majority of the DMRs are unique for preeclampsia. Few previously identified preeclampsia genes have been identified, however, the DMRs had gene associations in the P13 K-Akt signaling pathway and metabolic gene family, such as phospholipid signaling pathway. Preliminary validation of the DMR use as a potential maternal biomarker used a cross-validation analysis on the samples and provided 78% accuracy. Although prospective expanded clinical trials in first trimester pregnancies and clinical comparisons are required, the current study provides the potential proof of concept a preeclampsia epigenetic biomarker may exist. The availability of a preeclampsia PTB maternal susceptibility biomarker may facilitate clinical management and allow preventative medicine approaches to identify and treat the preeclampsia condition prior to its occurrence.
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    Genetic polymorphisms associated with adverse pregnancy outcomes in nulliparas
    (Springer Nature, 2024-05-07) Khan, Raiyan R.; Guerrero, Rafael F.; Wapner, Ronald J.; Hahn, Matthew W.; Raja, Anita; Salleb‑Aouissi, Ansaf; Grobman, William A.; Simhan, Hyagriv; Silver, Robert M.; Chung, Judith H.; Reddy, Uma M.; Radivojac, Predrag; Pe’er, Itsik; Haas, David M.; Obstetrics and Gynecology, School of Medicine
    Adverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well.
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    Intestinal barrier disruption with Plasmodium falciparum infection in pregnancy and risk of preterm birth: a cohort study
    (Elsevier, 2023) Wright, Julie K.; Weckman, Andrea M.; Ngai, Michelle; Stefanova, Veselina; Zhong, Kathleen; McDonald, Chloe R.; Elphinstone, Robyn E.; Conroy, Andrea L.; Coburn, Bryan A.; Madanitsa, Mwayi; Taylor, Steve M.; ter Kuile, Feiko O.; Kain, Kevin C.; Pediatrics, School of Medicine
    Background: Malaria in early pregnancy is a risk factor for preterm birth and is associated with sustained inflammation and dysregulated angiogenesis across gestation. This study investigated whether malaria is associated with increased gut leak and whether this contributes to systemic inflammation, altered angiogenesis, and preterm birth. Methods: We quantified plasma concentrations of gut leak markers, soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) from 1339 HIV-negative pregnant Malawians at <24 weeks gestational age. We assessed the relationship of sCD14 and LBP concentrations with markers of inflammation, angiogenesis, and L-arginine bioavailability and compared them between participants with and without malaria, and with and without preterm birth. Findings: Plasma concentrations of sCD14 and LBP were significantly higher in participants with malaria and were associated with parasite burden (p <0.0001, both analyses and analytes). The odds ratio for preterm birth associated with one log sCD14 was 2.67 (1.33 to 5.35, p = 0.006) and 1.63 (1.07-2.47, p = 0.023) for LBP. Both gut leak analytes were positively associated with increases in proinflammatory cytokines CRP, sTNFR2, IL18-BP, CHI3L1 and Angptl3 (p <0.05, all analytes) and sCD14 was significantly associated with angiogenic proteins Angpt-2, sENG and the sFLT:PlGF ratio (p <0.05, all analytes). sCD14 was negatively associated with L-arginine bioavailability (p <0.001). Interpretation: Malaria in early pregnancy is associated with intestinal barrier dysfunction, which is linked to an increased risk of preterm birth.
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    Maternal vitamin D status, fetal growth patterns, and adverse pregnancy outcomes in a multisite prospective pregnancy cohort
    (Elsevier, 2025) Beck, Celeste; Blue, Nathan R.; Silver, Robert M.; Na, Muzi; Grobman, William A.; Steller, Jonathan; Parry, Samuel; Scifres, Christina; Gernand, Alison D.; Obstetrics and Gynecology, School of Medicine
    Background: Few studies have examined maternal vitamin D status and fetal growth patterns across gestation. Furthermore, time points in pregnancy at which maternal vitamin D status is most critical for optimal fetal growth and pregnancy outcomes are uncertain. Objectives: Our objective was to examine whether first and second trimester maternal vitamin D status are associated with fetal growth patterns and pregnancy outcomes. Methods: We conducted a secondary analysis using data and samples from a multisite prospective cohort study of nulliparous pregnant females in the United States. We measured serum 25-hydroxyvitamin D (25(OH)D) for 351 participants at 6-13 and 16-21 weeks of gestation. Fetal growth was measured by ultrasound at 16-21 and 22-29 weeks of gestation, and neonatal anthropometric measures at birth. We constructed fetal growth curves using length, weight, and head circumference z-scores, and calculated risk of preterm birth (<37 wk) and small for gestational age (SGA). We examined outcomes across 25(OH)D concentrations assessed continuously, using Institute of Medicine (IOM) cutoffs (<50 compared with ≥50 nmol/L), and using exploratory cutoffs (<40, 40-59.9, 60-79.9, ≥80 nmol/L). Results: Vitamin D insufficiency (25(OH)D <50 nmol/L) was prevalent in 20% of participants in the first trimester. Each 10 nmol/L increase in first trimester 25(OH)D was associated with a 0.05 [95% confidence interval (CI): 0.01, 0.10] increase in length-for-age z-score but was not associated with weight or head circumference. There were no differences in risk of preterm birth or SGA using IOM cutoffs; participants with first trimester 25(OH)D <40 compared with ≥80 nmol/L had 4.35 (95% CI: 1.14, 16.55) times risk of preterm birth. Second trimester 25(OH)D was not associated with fetal growth patterns or with pregnancy outcomes. Conclusions: First trimester 25(OH)D is positively associated with linear growth. Low first trimester 25(OH)D (<40 nmol/L) is associated with a higher risk of preterm birth. Second trimester 25(OH)D is not associated with fetal growth or pregnancy outcomes assessed.
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    Palmitate and group B Streptococcus synergistically and differentially induce IL-1β from human gestational membranes
    (Frontiers Media, 2024-05-23) Gaddy, Jennifer A.; Moore, Rebecca E.; Lochner, Jonathan S.; Rogers, Lisa M.; Noble, Kristen N.; Giri, Ayush; Aronoff, David M.; Cliffel, David; Eastman, Alison J.; Medicine, School of Medicine
    Introduction: Rupture of the gestational membranes often precedes major pregnancy complications, including preterm labor and preterm birth. One major cause of inflammation in the gestational membranes, chorioamnionitis (CAM) is often a result of bacterial infection. The commensal bacterium Streptococcus agalactiae, or Group B Streptococcus (GBS) is a leading infectious cause of CAM. Obesity is on the rise worldwide and roughly 1 in 4 pregnancy complications is related to obesity, and individuals with obesity are also more likely to be colonized by GBS. The gestational membranes are comprised of several distinct cell layers which are, from outermost to innermost: maternally-derived decidual stromal cells (DSCs), fetal cytotrophoblasts (CTBs), fetal mesenchymal cells, and fetal amnion epithelial cells (AECs). In addition, the gestational membranes have several immune cell populations; macrophages are the most common phagocyte. Here we characterize the effects of palmitate, the most common long-chain saturated fatty acid, on the inflammatory response of each layer of the gestational membranes when infected with GBS, using human cell lines and primary human tissue. Results: Palmitate itself slightly but significantly augments GBS proliferation. Palmitate and GBS co-stimulation synergized to induce many inflammatory proteins and cytokines, particularly IL-1β and matrix metalloproteinase 9 from DSCs, CTBs, and macrophages, but not from AECs. Many of these findings are recapitulated when treating cells with palmitate and a TLR2 or TLR4 agonist, suggesting broad applicability of palmitate-pathogen synergy. Co-culture of macrophages with DSCs or CTBs, upon co-stimulation with GBS and palmitate, resulted in increased inflammatory responses, contrary to previous work in the absence of palmitate. In whole gestational membrane biopsies, the amnion layer appeared to dampen immune responses from the DSC and CTB layers (the choriodecidua) to GBS and palmitate co-stimulation. Addition of the monounsaturated fatty acid oleate, the most abundant monounsaturated fatty acid in circulation, dampened the proinflammatory effect of palmitate. Discussion: These studies reveal a complex interplay between the immunological response of the distinct layers of the gestational membrane to GBS infection and that such responses can be altered by exposure to long-chain saturated fatty acids. These data provide insight into how metabolic syndromes such as obesity might contribute to an increased risk for GBS disease during pregnancy.
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    Postnatal Depressive Symptoms Among Mothers and Fathers of Infants Born Preterm: Prevalence and Impacts on Children's Early Cognitive Function
    (Wolters Kluwer, 2016-01) Cheng, Erika R.; Kotelchuck, Milton; Gerstein, Emily D.; Taveras, Elsie M.; Poehlmann-Tynan, Julie; Department of Pediatrics, IU School of Medicine
    OBJECTIVE: Preterm birth is associated with lower cognitive functioning. One potential pathway is postnatal parental depression. The authors assessed depressive symptoms in mothers and fathers after preterm birth, and identified the impacts of both prematurity and parental depressive symptoms on children's early cognitive function. METHOD: Data were from the nationally representative Early Childhood Longitudinal Study, Birth Cohort (n = 5350). Depressive symptoms at 9 months were assessed by the Center for Epidemiologic Studies Depression Scale (CESD) and children's cognitive function at 24 months by the Bayley Short Form, Research Edition. Weighted generalized estimating equation models examined the extent to which preterm birth, and mothers' and fathers' postnatal depressive symptoms impacted children's cognitive function at 24 months, and whether the association between preterm birth and 24-month cognitive function was mediated by parental depressive symptoms. RESULTS: At 9 months, fathers of very preterm (<32 weeks gestation) and moderate/late preterm (32-37 weeks gestation) infants had higher CESD scores than fathers of term-born (≥37 weeks gestation) infants (p value = .02); preterm birth was not associated with maternal depressive symptoms. In multivariable analyses, preterm birth was associated with lower cognitive function at 24 months; this association was unaffected by adjustment for parental depressive symptoms. Fathers', but not mothers', postnatal depressive symptoms predicted lower cognitive function in the fully adjusted model (β = -0.11, 95% confidence interval, -0.18 to -0.03). CONCLUSION: Fathers of preterm infants have more postnatal depressive symptomology than fathers of term-born infants. Fathers' depressive symptoms also negatively impact children's early cognitive function. The national findings support early identification and treatment of fathers of preterm infants with depressive symptoms.