Search

Women with gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB) have excess cardiovascular disease compared with those with uncomplicated births, perhaps related to prepregnancy inflammation, dysmetabolism, or endothelial dysfunction. We included 1238 women in the Coronary Artery Risk Development in Young Adults Study (1985-2011) with 2215 births classified according to outcomes (term, uncomplicated births were the referent). Using repeated measures analysis of variance, we estimated prepregnancy and postpregnancy biomarkers, as well as biomarker change according to pregnancy outcomes, adjusted for confounders. GDM and term HDP groups had higher prepregnancy high-sensitivity C-reactive protein (hsCRP) (+0.37 [95% CI, 0.08-0.65]; +0.29 [95% CI, 0.04-0.55] log mg/L), higher leptin (+0.29 [95% CI, 0.09-0.50]; +0.37 [95% CI, 0.17-0.56] log ng/ml), and lower adiponectin (-0.25 [95% CI, -0.36 to -0.13); -0.11 [95% CI, -0.22 to -0.01] log ng/ml) values than those with uncomplicated births, and these profiles persisted in magnitude postpregnancy. Controlling for body mass index attenuated most profiles, except that lower prepregnancy adiponectin remained associated with GDM. PTB without HDP or GDM was related to lower prepregnancy hsCRP and soluble intercellular adhesion molecule-1 (-0.31 [95% CI, -0.56 to -0.06] log mg/L; -0.05 [95% CI, -0.09 to -0.01] log ng/ml) and a larger leptin increase from before to after pregnancy (+0.20 [95% CI, 0.02-0.37] log ng/ml). Prepregnancy inflammation and metabolic dysfunction contributed to GDM and HDP, perhaps due to higher body mass index. PTB may be related to adverse metabolic changes postpregnancy, although the unexpected endothelial biomarker profile warrants further study., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The complex physiologic process of parturition includes the onset of labor, which requires the orchestrated stimulation of a common pathway involving uterine contractility, cervical ripening, and chorioamniotic membrane activation. However, the labor-specific processes taking place in these tissues have limited use as predictive biomarkers unless they can be probed in non-invasive samples, such as the peripheral blood. Herein, we utilized a transcriptomic dataset to assess labor-specific changes in the peripheral blood of women who delivered at term. We identified a set of genes that were differentially expressed with labor and enriched for immunological processes, and these gene expression changes were strongly correlated with results from prior studies, providing in silico validation of our findings. We then identified significant correlations between labor-specific transcriptomic changes in the maternal circulation and those detected in the chorioamniotic membranes, myometrium, and cervix of women at term, demonstrating that tissue-specific labor signatures are partly mirrored in the peripheral blood. Finally, we demonstrated a significant overlap between the peripheral blood transcriptomic changes in term parturition and those observed in asymptomatic women, prior to the diagnosis of preterm prelabor rupture of the membranes, who ultimately delivered preterm. Collectively, we provide evidence that the normal process of labor at term is characterized by a unique immunological expression signature, which may serve as a useful tool for assessing labor status and for potentially identifying women at risk for preterm birth., (© The Author(s) 2021. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Low-dose adrenocorticotropic hormone stimulation testing (LDST) can be used to diagnose central adrenal insufficiency. However, uncertainty remains over optimal times to draw serum cortisol levels., Objective: To determine optimal times to draw serum cortisol levels for the LDST in neonates., Design: A retrospective chart review of LDSTs performed on neonates from January 1, 2009 to September 30, 2017., Setting: Children's Hospital of Eastern Ontario (CHEO), a tertiary-care outborn pediatric center., Patients: Forty-nine patients were included: 23 (46.9%) born at term, 12 (24.5%) born very preterm to late preterm, and 14 (28.6%) born extremely preterm., Intervention: Cortisol levels were drawn at baseline and 15, 30, and 60 minutes following administration of Cortrosyn 1 mcg/kg (maximum dose 1 mcg)., Main Outcome Measure: Timing of peak cortisol level and marginal value of drawing a second and third cortisol sample at 15, 30, or 60 minutes was determined., Results: Cortisol peaked at 15-, 30-, and 60-minute sampling times for 4%, 27%, and 69% of patients, respectively. The probability that a failed LDST changes to a pass by adding a 15- or 30-minute sample to the superior 60 minute sample is 5.6% (1% to 25.8%) and 11% (3.1% to 32.6%), respectively, for a cortisol pass threshold of 18.1mcg/dL (500 nmol/L)., Conclusions: In contrast to studies of older children, we found that the majority of neonatal LDST cortisol peaks occurred at the 60-minute sampling time with the addition of a 30-minute sample providing substantial benefit. It is questionable if a 15-minute sample provides any benefit, making a case to revise LDST protocols to sample cortisol later for neonates., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Clinical trials of interventions for preventing malaria in pregnancy often use measures of malaria at delivery as their primary outcome. Although the objective of these interventions is to improve birth outcomes, data on associations between different measures of malaria at delivery and adverse birth outcomes are limited., Methods: Data came from 637 Ugandan women enrolled in a randomized controlled trial of intermittent preventive treatment of malaria in pregnancy. Malaria at delivery was detected using peripheral and placental blood microscopy, placental blood loop-mediated isothermal amplification (LAMP), and placental histopathology. Multivariate analyses were used to estimate associations between measures of malaria at delivery and risks of low birth weight (LBW), small for gestational age (SGA), and preterm birth (PTB)., Results: Detection of malaria parasites by microscopy or LAMP was not associated with adverse birth outcomes. Presence of malaria pigment detected by histopathology in ≥30% of high-powered fields was strongly associated with LBW (adjusted risk ratio [aRR] = 3.42, P = .02) and SGA (aRR = 4.24, P < .001) but not PTB (aRR = 0.88, P = .87)., Conclusions: A semiquantitative classification system based on histopathologically detected malaria pigment provided the best surrogate measure of adverse birth outcomes in a high-transmission setting and should be considered for use in malaria in pregnancy intervention studies., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Exosomes are membrane-bound nanovesicles that transport molecular signals between cells. This study determined changes in maternal plasma exosome proteomics contents in term and preterm births. Maternal plasma (MP) samples were collected from group 1: term not in labor (TNIL, n = 13); group 2: term in labor (TL, n = 11); group 3: preterm premature rupture of membranes (pPROM, n = 8); and group 4: preterm birth (PTB, n = 13). Exosomes isolated from plasma by differential density centrifugation followed by size exclusion chromatography were characterized by morphology (electron microscopy), quantity and size (nanoparticle tracking analysis), and markers (western blot). A quantitative, information-independent acquisition [sequential windowed acquisition of all theoretical mass spectra (SWATH-MS)] approach was used to determine the protein profile in exosomes. Ingenuity Pathway Analysis determined pathways associated with the protein profile identified in exosomes. MP exosomes were spherical, had a mean diameter of 120 nm, and were positive for exosomal proteins CD63 and TSG101 irrespective of pregnancy status. No distinct changes in exosome quantities were seen in maternal circulation across the groups. SWATH-MS identified 72 statistically significant proteins across the groups studied. Bioinformatics analysis showed the proteins within the exosomes in TNIL, TL, pPROM, and PTB target pathways mainly associated with inflammatory and metabolic signals. Exosomal data suggest that homeostatic imbalances, specifically inflammatory and endocrine signaling, might disrupt pregnancy maintenance resulting in labor-related changes both at term and preterm. Reflection of physiologic changes in exosomes is suggestive of its usefulness as biomarkers and cellular function indicators., (Copyright © 2019 Endocrine Society.)

Context: Overt thyroid disease in pregnancy is a known risk factor for abnormal fetal growth and development. Data on the effects of milder forms of variation in maternal thyroid function on intrauterine growth are less well examined., Objective: We explored these associations using repeated thyroid hormone and ultrasound measurements., Design, Setting, and Participants: Data were obtained from 439 pregnant women without diagnosed thyroid disease who were participants in a case-control study of preterm birth nested within an ongoing prospective birth cohort in Boston, Massachusetts., Main Outcome Measures: Ultrasound and delivery indices of fetal growth were standardized to those measured in a larger population., Results: At median 10, 18, and 26 weeks of gestation, we observed significant inverse associations between free thyroxine (FT4) and birth weight z scores, with the strongest association detected at median 10 weeks, at which time a 10% increase in FT4 was associated with a 0.02 z score decrease (∼8.5 g) in birth weight (β = -0.41 for ln-transformed FT4; 95% confidence interval, -0.64 to -0.18). FT4 was also inversely associated with repeated measurements of estimated fetal weight, head circumference, and abdominal circumference. We observed weaker inverse associations for total T4 and a positive relationship between total triiodothyronine and birth weight z scores. We did not observe any associations for thyroid-stimulating hormone., Conclusion: In pregnant women without overt thyroid disease, subclinical changes in thyroid function parameters may influence fetal growth.

Study Question: Is supraphysiologic estradiol (E2) an independent predictor of low birth weight (LBW) in singletons born after fresh IVF-embryo transfer (ET) cycles?, Summary Answer: Our results suggest that E2 > 2500 pg/ml is an independent predictor for LBW in full-term singletons born to normal responder patients undergoing fresh IVF-ET cycles., What Is Known Already: The pathogenesis of LBW in IVF singletons remains unknown. However, recent studies have suggested that the hyperestrogenic milieu generated during ovarian stimulation may create a sub-optimal peri-implantation environment, leading to placental dysfunction, and therefore, LBW., Study Design, Size, Duration: Retrospective cohort study of normal responder patients, <40 years old, undergoing fresh IVF-ET cycles resulting in live singleton births between January 2005 and June 2014., Participants/materials, Setting, Methods: A total of 6419 patients had live births after fresh IVF-ET during the study period, of which 2348 (36.6%) patients were excluded due to multiple gestation, vanishing twins or incomplete records. Perinatal outcomes recorded for all patients included birth weight, gestational age (GA) at delivery, mode of delivery and gender. Term birth, preterm birth (PTB) and LBW incidence proportions were plotted against E2 level on the day of trigger. The term LBW incidence proportion (i.e. singletons born at GA ≥ 37 weeks with birth weight <2500 g) was considered the primary outcome of interest., Main Results and the Role of Chance: A total of 4071 patients with live singleton births were included. The median age, BMI, E2 level and birth weight for the study cohort was 36 (33-39) years, 22.3 (20.4-25.0) kg/m2, 1554 (1112.7-2179) pg/ml and 3289 (2920-3628) g, respectively. The incidence proportion of LBW rose from 6.4% (E2 2001-2500 pg/ml) to 20.7% (E2 3501-4000 pg/ml), without a corresponding rise in the incidence proportion of PTB. The odds of term LBW with E2 > 2500 pg/ml were 6.1-7.9 times higher compared to the referent E2 group. Multivariable logistic regression analysis revealed that E2 was an independent predictor for term LBW, even after adjusting for age, BMI, race, parity, infertility diagnosis, duration of ovarian stimulation, gonadotropin dosage and method of insemination (adjusted odds ratio 10.8, 95% CI 9.2-12.5). Receiver operating characteristic analysis generated an AUC estimate of 0.85 for E2 level as a predictor of LBW., Limitations Reasons for Caution: The current study did not include analyses of hypertensive disorders of pregnancy or placental abnormalities. Furthermore, all patients were normal responders and of normal BMI, possibly limiting the overall generalizability of the study. Finally, as with any retrospective study, prospective data are required to validate the role of E2 in predicting LBW., Wider Implications of the Findings: Our results emphasize the importance of minimizing the supraphysiologic elevations of E2 levels during ovarian stimulation in fresh IVF-ET cycles. This, in turn, can optimize the early peri-implantation environment and mitigate adverse perinatal outcomes such as LBW., Study Funding/competing Interest(s): Dr Paul J. Christos was partially supported by the following grant: Clinical and Translational Science Center at Weill Cornell Medical College (UL1-TR000457-06)., Trial Registration Number: N/A., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

Background: Maternal retinol-binding protein 4 (RBP4) and lipids may relate to preeclampsia and preterm birth risk but longitudinal data are lacking. This study examines these biomarkers longitudinally during pregnancy in relation to preeclampsia and preterm birth risk., Methods: Maternal serum samples from the Calcium for Preeclampsia Prevention (CPEP) trial were analyzed at baseline: average 15 gestational weeks; mid-pregnancy: average 27 weeks; and at >34 weeks. We measured RBP4, total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides and lipoprotein (a) (Lp(a)). Cross-sectional logistic regression analyses estimated the odds ratio (OR) and 95% confidence intervals (CI) for preterm preeclampsia (n = 63), term preeclampsia (n = 104), and preterm delivery (n = 160) associated with RBP4 and lipids at baseline and mid-pregnancy compared with controls (n = 136). Longitudinal trajectories across pregnancy were assessed using mixed linear models with fixed effects. Adjusted models included clinical and demographic factors., Results: RBP4 concentrations at baseline and mid-pregnancy were associated with a 4- to 8-fold increase in preterm preeclampsia risk but were not associated with term preeclampsia. RBP4 measured mid-pregnancy was also associated with preterm birth (OR = 6.67, 95% CI: 1.65, 26.84). Higher triglyceride concentrations in mid-pregnancy were associated with a 2- to 4-fold increased risk for both preeclampsia and preterm birth. Longitudinal models demonstrate that both preterm preeclampsia and preterm birth cases had elevated RBP4 throughout gestation., Conclusions: Elevated RBP4 is detectable early in pregnancy and its strong relation with preterm preeclampsia merits further investigation and confirmation to evaluate its potential use as a predictor, particularly among high-risk women., (© Published by Oxford University Press on behalf of American Journal of Hypertension Ltd 2017. This work is written by (a) US Government employees(s) and is in the public domain in the US.)

Background: Thyroid disease during pregnancy is associated with multiple adverse maternal and fetal outcomes. In particular, multiple observational studies have demonstrated an association between the presence of thyroid antibodies in euthyroid women in the first trimester of miscarriage and an increased rate of spontaneous miscarriage and preterm delivery. The present study is a prospective intervention trial of the effect of levothyroxine on the rate of miscarriage and preterm delivery in euthyroid thyroid-antibody positive women in the first trimester of pregnancy., Methods: A total of 8530 women in the first trimester of pregnancy in Southern Italy were screened for TSH and thyroid antibodies. Group A consisted of 198 euthyroid thyroid antibody positive women treated with levothyroxine, group B consisted of 195 untreated euthyroid thyroid antibody positive women, and group C consisted of 197 untreated thyroid antibody negative women., Results: The rate of miscarriage did not differ between the 3 groups (11.6%, 14.9%, and 8.1 %, P = .11). The rate of preterm delivery between the 3 groups was 6.9%, 10.8%, and 2.8% and was statistically significant (P = .01). The rate of preterm delivery was significantly different between groups B and C (P = .02) but was not significantly different between groups A and B (P = .27)., Conclusions: In conclusion, the present study found that levothyroxine intervention had no impact on the rate of miscarriage and preterm delivery in euthyroid thyroid antibody positive women.

Study Objectives: Poor sleep promotes inflammation. In turn, inflammation is a causal mechanism in term as well as preterm parturition. In the United States, a persistent racial disparity in preterm birth exists, with African Americans showing ∼1.5 times greater risk. This study examined associations among sleep quality, serum proinflammatory cytokines, and length of gestation in a racially diverse sample of 138 pregnant women., Design: Observational., Measurements: Women completed the Pittsburgh Sleep Quality Index (PSQI) and other psychosocial and behavioral measures during midpregnancy. Serum levels of interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor (TNF)-α were determined by high-sensitivity assays. Birth outcomes were determined via medical record review., Results: Among African American women (n = 79), shorter gestation was predicted by poorer overall sleep (rs = -0.35, P = 0.002) as well the following PSQI subscales: subjective sleep quality (rs = -0.34, P = 0.002), sleep latency (rs = -0.27, P = 0.02), and sleep efficiency (rs = -0.27, P = 0.02). African American women with poor sleep quality (PSQI > 5) had 10.2 times the odds of preterm birth compared to those with good sleep quality. In contrast, among European American women (n = 53), gestational length was not significantly predicted by sleep quality (Ps > 0.12). Bootstrapping analyses showed that, among African Americans, IL-8 significantly mediated the association between sleep quality and length of gestation (indirect effect estimate -0.029; 95% confidence interval -0.06, -0.002)., Conclusions: The data provide novel evidence that African American women exhibit greater inflammation in response to sleep disturbance than European American women and these effects correspond with length of gestation. Racial differences in susceptibility to sleep induced immune dysregulation may contribute to marked racial disparities in preterm birth., (© 2015 Associated Professional Sleep Societies, LLC.)

Infection-induced inflammation, frequently associated with increased production of proinflammatory cytokines, is considered a significant contributor to preterm birth. A G protein-coupled cannabinoid receptor 2 (CB2), encoded by Cnr2, is expressed in various immune cells and was shown to modulate immune responses. We show here that Cnr2, but not Cnr1, deficient mice are resistant to lipopolysaccharide (LPS)-driven preterm birth and suppression of serum progesterone levels. After LPS challenge, Cnr2(-/-) mice exhibited increased serum levels of IL-10 with decreased IL-6 levels. These changes were associated with reduced LPS-induced Ptgs2 expression at the maternal-conceptus interface on day 16 of pregnancy. LPS stimulation of Cnr2(-/-) dendritic cells in vitro resulted in increased IL-10 with reduced IL-6 production and correlated with increased cAMP accumulation. Collectively, our results suggest that increased IL-10 production occurring via augmented cAMP accumulation represents a potential mechanism for the resistance of Cnr2(-/-) mice to LPS-induced preterm birth. These results may have clinical relevance, because currently, there are limited options to prevent preterm birth.

We considered that accumulation of nonesterified (free) fatty acids (NEFAs) in the first trimester of pregnancy would mark women at excess risk of spontaneous preterm birth (sPTB) and examined the interplay between NEFAs, lipids, and other markers to explore pathways to sPTB. In a case-control study nested in the Pregnancy Exposures and Preeclampsia Prevention Study (Pittsburgh, Pennsylvania, 1997-2001), we assayed NEFA levels in nonfasting serum collected at a mean gestational week of 9.4 (range, 4-20 weeks) in 115 women with sPTB (<37 weeks) and 222 women with births occurring at ≥37 weeks. C-reactive protein, total cholesterol, low-density lipoprotein and high-density lipoprotein (HDL) cholesterol, triglycerides, and uric acid were also measured. Polytomous logistic regression models were used to evaluate tertiles of NEFA levels and sPTB at <34 weeks and 34-36 weeks; factor analysis was used to characterize patterns of biomarkers. Women with NEFA levels in the highest tertile versus the lowest were 2.02 (95% confidence interval: 1.13, 3.48) times more likely to have sPTB, after adjustment for covariates. Risk of sPTB before 34 weeks was particularly high among women with high NEFA levels (odds ratio = 3.73, 95% confidence interval: 1.33, 10.44). Six biomarker patterns were identified, and 2 were associated with sPTB: 1) increasing NEFA and HDL cholesterol levels and 2) family history of gestational hypertension. NEFA levels early in pregnancy were independently associated with sPTB, particularly before 34 weeks. We also detected a novel risk pattern suggesting that NEFAs together with HDL cholesterol may be related to sPTB.

Context: Shortly after birth, pituitary gonadotropin secretion transiently activates in both sexes, and this surge is more robust in preterm (PT) than in full-term (FT) infants. In boys, the gonadotropin surge is associated with testicular activity and is considered an important part of normal reproductive development. In contrast, gonadal activation and its consequences in infant girls are poorly understood., Objective: Our objective was to evaluate the association of postnatal ovarian activity with simultaneous changes in estrogen target tissues in FT and PT girls., Patients and Methods: We measured urinary estradiol (E₂) levels in 29 FT and 34 PT girls using a mass spectrometric method from 1 week (D7) to 6 months of age (M1-M6). To assess the contribution of ovarian E₂ on urinary E₂ levels, the levels in girls were compared with the levels of boys of similar cohorts (29 FT and 33 PT boys). E₂ levels were compared with simultaneous changes in estrogenic target tissues including mammary glands in both sexes and uterus and vulvar epithelium in girls., Results: Median urinary E₂ levels increased after D7 in girls, but not in boys. Mammary gland diameter was larger in girls than in boys from M4 in FT (P < .001) and M2 in PT infants (P < .0001). In PT girls, E₂ levels increased at term and were then higher than those in FT girls (P < .0001). Urinary E₂ levels in PT girls were positively associated with mammary gland and uterine growth., Conclusions: These findings indicate that gonadal steroidogenesis activates during the postnatal gonadotropin surge in girls. In addition, the resulting elevated E₂ levels affect target tissues, suggesting that postnatal pituitary-ovarian activation plays a role in normal female reproductive development.

Large numbers of polymorphonuclear leukocytes in the amnion and chorion define histological chorioamnionitis (HCA), a condition linked to spontaneous preterm delivery (PTD). Less is known about placental patterns of mononuclear leukocyte (MNL) density and PTD. In this prospective study (1998-2004), women were sampled from 52 clinics in 5 Michigan communities and enrolled at 16-27 weeks' gestation. HCA and MNL distributions in delivered placentas were evaluated microscopically in a subcohort (290 preterm, 823 term). Midpregnancy biomarkers from maternal blood (i.e., C-reactive protein (CRP), corticotropin-releasing hormone, and cytokines) were compared among term and PTD subjects grouped by presence/absence of HCA and high MNL density. A density of more than 10 MNLs per high-power field in the chorion of the membrane roll, referred to as MNL-CMR, was associated with medically indicated PTD (odds ratio = 2.2, 95% confidence interval: 1.3, 3.6) and spontaneous PTD (odds ratio = 2.5, 95% confidence interval: 1.7, 3.7). Associations persisted after removal of women with HCA-positive placentas, abruption, hypertensive disorders, or obesity. HCA-associated PTD showed higher CRP and cytokine levels. MNL-CMR-associated PTD showed higher CRP and corticotropin-releasing hormone levels. These data suggest that an MNL infiltrate in the chorion of the membrane roll marks PTD pathways that are distinct from HCA and not entirely explained by pregnancy complications.

Context: Associations between small size at birth and abnormal cardiovascular parameters in later life have been reported. It is, however, unknown whether the effect of a small size at birth on cardiovascular risk factors in later life is due to a small size for gestational age or due to prematurity. Due to advances in neonatal care, survival of preterm infants has significantly improved, and nowadays an increasing number of these children reach adulthood. It is, therefore, of increasing importance to assess the long-term effect of prematurity on determinants for cardiovascular disease., Objective: The aim of the study was to assess the long-term effects of gestational age and particularly preterm birth on lipid levels and fat mass in early adulthood., Design and Patients: A cross-sectional study was conducted with 455 healthy subjects, aged 18 to 24 yr; 167 preterm subjects were compared with 288 full-term subjects., Outcome Measure: Total fat mass, trunk fat mass, and limb fat mass were determined by dual-energy x-ray absorptiometry. Furthermore, fasting lipid levels (total cholesterol, low-density lipoprotein, triglyceride, apolipoprotein B, lipoprotein a, high-density lipoprotein, and apolipoprotein A-I) were measured., Results: Preterm subjects had a significantly higher percentage of total fat mass, trunk fat mass, and limb fat mass than subjects born term. Furthermore, preterm subjects had significantly lower serum lipoprotein a levels and higher apolipoprotein A-I levels than term subjects. Multiple linear regression analyses to assess the association between gestational age and fat mass and lipid levels showed similar results., Conclusion: In our cohort of 455 young adults, preterm birth was associated with more total fat mass, trunk fat, and limb fat mass but a relatively favorable lipid profile.

While elevated levels of proinflammatory cytokines are clearly associated with preterm birth, the relation between cytokines and fetal growth is unclear. The authors examined associations between umbilical cord serum cytokine concentrations and risk of small-for-gestational-age (SGA) and preterm birth. This cross-sectional analysis was nested within a National Institute of Child Health and Human Development-University of Alabama population-based cohort study of high-risk prenatal care patients in Jefferson County, Alabama. Patients were enrolled between 1985 and 1988. For 370 singletons, umbilical cord serum concentrations of interferon gamma (IFN-gamma), tumor necrosis factor alpha, and interleukins 12p70, 4, and 10 were determined. Associations between each cytokine and SGA and preterm delivery were evaluated using log binomial regression. Increasing log concentration of tumor necrosis factor alpha was associated with an increased risk of preterm birth (risk ratio (RR) = 2.00, 95% confidence interval (CI): 1.31, 3.06). IFN-gamma was associated with a decreased risk of SGA birth (RR = 0.78, 95% CI: 0.61, 1.01). After stratification for preterm birth status, the association between IFN-gamma concentration and SGA birth was pronounced among preterm babies (RR = 0.56, 95% CI: 0.31, 1.01). The observations regarding IFN-gamma, which is involved in the activation of adaptive immune responses and regulation of trophoblast function, suggest that IFN-gamma levels at birth may be related to fetal growth restriction.

Background: The role of maternal anaemia in preterm birth remains poorly defined, and the association between anaemia and preterm birth clinical subtypes remain unclear. We examined if maternal anaemia exposure both within and across trimesters during gestation is associated with preterm birth., Methods: This was a secondary analysis of data from a population-based prospective cohort study in 13 counties of East China (1993-96). All singleton live births delivered at 20-44 weeks to women with at least one haemoglobin measure during pregnancy were included (n = 160 700). Risk of preterm birth (<37 weeks) was examined by clinical subtypes, namely, preterm premature rupture of membranes (PROM), spontaneous preterm labour and medically indicated preterm birth. Haemoglobin changes across trimesters were assessed as proxy of haemo-dilution and haemo-concentration. Multivariable Cox proportional hazards regression models were fitted., Results: Preterm birth rates of preterm birth were 4.1% for anaemic and 5% for non-anaemic women (P < 0.05). Compared with haemoglobin of 11 g/dl (reference), values

Objective: To determine the influence of gestational age and fetal growth restriction on the cord blood adipokine profile, IGF1, and ghrelin levels, and their relationship with glucose metabolism., Study Design: One hundred and ninety newborns (99 preterm and 91 full term) were studied and, according to their anthropometry at birth, classified as small (SGA) or adequate for gestational age (AGA)., Methods: Venous cord blood serum levels of IGF1, IGF binding protein 3 (IGFBP-3), adiponectin, resistin, leptin, soluble leptin receptor (sOB-R), tumoral necrosis factor-alpha, interleukin 6 (IL-6), total ghrelin, and acylated ghrelin were determined and compared between preterm and full-term, as well as between SGA and AGA, newborns. Correlations with newborn weight, gestational age, and homeostatic model assessment (HOMA) index, as an index of insulin resistance, were determined., Results: Preterm newborns had higher HOMA, sOB-R, resistin, and IL-6 and lower IGF1, IGFBP-3, leptin, and adiponectin levels than full-term newborns. SGA had lower IGF1, IGFBP-3, leptin, IL-6, and adiponectin and higher sOB-R and total ghrelin than AGA newborns. Adiponectin and HOMA showed independent positive and negative correlations with gestational age respectively, but not with neonatal weight. Birth weight was correlated positively with IGF1 and leptin levels and negatively with total ghrelin ones., Conclusions: Our findings suggest that the lack of proper acquisition of adipose tissue by the fetus either due to prematurity or to fetal growth restriction is associated with changes in the cord blood adipokine profile that may contribute to the impairment of glucose metabolism.

Context: Clinical prediction of preterm delivery is largely ineffective, and the mechanism mediating progesterone (P) withdrawal and estrogen activation at the onset of human labor is unclear., Objectives: Our objectives were to determine associations of rates of change of circulating maternal CRH in midpregnancy with preterm delivery, CRH with estriol (E3) concentrations in late pregnancy, and predelivery changes in the ratios of E3, estradiol (E2), and P., Design and Setting: A cohort of 500 pregnant women was followed from first antenatal visits to delivery during the period 2000-2004 at John Hunter Hospital, New South Wales, Australia, a tertiary care obstetric hospital., Patients: Unselected subjects were recruited (including women with multiple gestations) and serial blood samples obtained., Main Outcome Measures: CRH daily percentage change in term and preterm singletons at 26 wk, ratios E3/E2, P/E3, and P/E2 and the association between E3 and CRH concentrations in the last month of pregnancy (with spontaneous labor onset) were assessed., Results: CRH percentage daily change was significantly higher in preterm than term singletons at 26 wk (medians 3.09 and 2.73; P = 0.003). In late pregnancy, CRH and E3 concentrations were significantly positively associated (P = 0.003). E3/E2 increased, P/E3 decreased, and P/E2 was unchanged in the month before delivery (medians: E3/E2, 7.04 and 10.59, P < 0.001; P/E3, 1.55 and 0.98, P < 0.001; P/E2, 11.78 and 10.79, P = 0.07)., Conclusions: The very rapid rise of CRH in late pregnancy is associated with an E3 surge and critically altered P/E3 and E3/E2 ratios that create an estrogenic environment at the onset of labor. Our evidence provides a rationale for the use of CRH in predicting preterm birth and informs approaches to delaying labor using P supplementation.

Context: Preterm birth is followed by a decrease in circulatory levels of IGF-I and IGF binding protein (IGFBP)-3, proteins with important neurogenic and angiogenic properties., Objective: Our objective was to evaluate the effects of iv administration of fresh-frozen plasma (FFP) from adult donors on circulatory levels of IGF-I and IGFBP-3 in extremely preterm infants., Design, Setting, and Patients: A prospective cohort study was performed in 20 extremely preterm infants [mean (SD) gestational age 25.3 (1.3) wk] with clinical requirement of FFP during the first postnatal week. Sampling was performed before initiation of transfusion, directly after, and at 6, 12, 24, and 48 h after completed FFP transfusion., Main Outcome Measures: Concentrations of IGF-I and IGFBP-3 before and after transfusion of FFP were determined., Results: FFP with a mean (SD) volume of 11 ml/kg (3.1) was administered at a median postnatal age of 2 d (range 1-7). Mean (SD) IGF-I and IGFBP-3 concentrations in administered FFP were 130 (39) and 2840 microg/liter (615), respectively. Immediately after FFP transfusion, mean (SD) concentrations of IGF-I increased by 133% from 11 (6.4) to 25 microg/liter (9.3) (P < 0.001) and IGFBP-3 by 61% from 815 (451) to 1311 microg/liter (508) (P < 0.001). Concentrations of IGF-I and IGFBP-3 remained higher at 6 (P < 0.001, P = 0.009) and 12 h (P = 0.017, P = 0.018), respectively, as compared with concentrations before FFP transfusion. Typical half-life of administrated IGF-I was 3.4 h for a 1-kg infant., Conclusion: Transfusion of FFP to extremely preterm infants during the first postnatal week elevates levels of IGF-I and IGFBP-3.

Systemic maternal infections have been associated with preterm delivery. The authors examined the association of C-reactive protein (CRP), a marker of inflammation, with preterm delivery. This nested case-control study was conducted within Project Viva in Massachusetts between 1999 and 2002. Subjects were 117 women who delivered preterm (< 37 weeks' gestation) and 117 controls (term deliveries) matched on age, race/ethnicity, and smoking status. High-sensitivity CRP assays were performed on early-pregnancy (5.3-19.3 weeks' gestation) plasma samples. Odds ratios and 95% confidence intervals were estimated by using conditional logistic regression adjusted for matching factors, gestational age at blood collection, and prepregnancy body mass index. Median concentration of CRP was 3.2 mg/liter in cases versus 2.4 mg/liter in controls. No significant association was found between quartiles of CRP and preterm delivery. However, CRP levels exceeding the threshold defined in the literature were associated with increased risk of preterm delivery (odds ratio = 2.55, 95% confidence interval: 1.05, 6.02 for CRP > or = 8 mg/liter). The association was stronger among cases who experienced spontaneous delivery (odds ratio = 4.64, 95% confidence interval: 0.94, 22.96) versus indicated delivery (odds ratio = 1.42, 95% confidence interval: 0.44, 4.61). These findings suggest that very high CRP levels in early pregnancy are associated with preterm delivery.

The pesticide p,p'-dichlorodiphenyltrichloroethane (DDT) and its persistent metabolite p,p'-dichlorodiphenyldichloroethylene (DDE) are associated with negative reproductive outcomes in animals. In humans, however, the findings are inconsistent. Using data from the Child Health and Development Studies, a longitudinal study of 20,754 pregnancies among San Francisco Bay Area women from 1959 to 1967, the authors examined the effects of maternal serum DDT and DDE concentrations on preterm birth, small-for-gestational-age birth, birth weight, and gestational age in 420 male subjects. Data were analyzed using multivariate logistic regression for preterm and small-for-gestational-age birth and linear regression for birth weight and gestational age. Median serum concentrations of DDE were 43 mug/liter (interquartile range: 32-57; range: 7-153) and of DDT were 11 mug/liter (interquartile range: 8-16; range: 3-72), several times higher than current US concentrations. The adjusted odds ratio for preterm birth was 1.28 (95% confidence interval (CI): 0.73, 2.23) for DDE and 0.94 (95% CI: 0.50, 1.78) for DDT. For small-for-gestational-age birth, the adjusted odds ratio was 0.75 (95% CI: 0.44, 1.26) for DDE and 0.69 (95% CI: 0.73, 1.27) for DDT; none of the study results achieved statistical significance. Given the persistence of DDT in the environment and its continuing role in malaria control, studies using more robust data should continue to assess this relation.