Talk:Birth - Preterm

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Cite this page: Hill, M.A. (2020, June 7) Embryology Birth - Preterm. Retrieved from


Risk of spontaneous preterm birth and fetal growth associates with fetal SLIT2

PLoS Genet. 2019 Jun 13;15(6):e1008107. doi: 10.1371/journal.pgen.1008107. eCollection 2019 Jun.

Tiensuu H1, Haapalainen AM1, Karjalainen MK1, Pasanen A1, Huusko JM1,2, Marttila R1, Ojaniemi M1, Muglia LJ2, Hallman M1, Rämet M1,3.

Spontaneous preterm birth (SPTB) is the leading cause of neonatal death and morbidity worldwide. Both maternal and fetal genetic factors likely contribute to SPTB. We performed a genome-wide association study (GWAS) on a population of Finnish origin that included 247 infants with SPTB (gestational age [GA] < 36 weeks) and 419 term controls (GA 38-41 weeks). The strongest signal came within the gene encoding slit guidance ligand 2 (SLIT2; rs116461311, minor allele frequency 0.05, p = 1.6×10-6). Pathway analysis revealed the top-ranking pathway was axon guidance, which includes SLIT2. In 172 very preterm-born infants (GA <32 weeks), rs116461311 was clearly overrepresented (odds ratio 4.06, p = 1.55×10-7). SLIT2 variants were associated with SPTB in another European population that comprised 260 very preterm infants and 9,630 controls. To gain functional insight, we used immunohistochemistry to visualize SLIT2 and its receptor ROBO1 in placentas from spontaneous preterm and term births. Both SLIT2 and ROBO1 were located in villous and decidual trophoblasts of embryonic origin. Based on qRT-PCR, the mRNA levels of SLIT2 and ROBO1 were higher in the basal plate of SPTB placentas compared to those from term or elective preterm deliveries. In addition, in spontaneous term and preterm births, placental SLIT2 expression was correlated with variations in fetal growth. Knockdown of ROBO1 in trophoblast-derived HTR8/SVneo cells by siRNA indicated that it regulate expression of several pregnancy-specific beta-1-glycoprotein (PSG) genes and genes involved in inflammation. Our results show that the fetal SLIT2 variant and both SLIT2 and ROBO1 expression in placenta and trophoblast cells may be correlated with susceptibility to SPTB. SLIT2-ROBO1 signaling was linked with regulation of genes involved in inflammation, PSG genes, decidualization and fetal growth. We propose that this receptor-ligand couple is a component of the signaling network that promotes SPTB.

PMID: 31194736 DOI: 10.1371/journal.pgen.1008107

Second Trimester Serum Biomarker Screen for Fetal Aneuploidies as a Predictor of Preterm Delivery: A Population-Based Study

Gynecol Obstet Invest. 2019 Jan 2:1-8. doi: 10.1159/000495614. [Epub ahead of print]

Nunthapiwat S, Sekararithi R, Wanapirak C, Sirichotiyakul S, Tongprasert F, Srisupundit K, Luewan S, Tongsong T. Abstract OBJECTIVE: To determine the association between second-trimester serum Down syndrome screening (alpha-fetoprotein [AFP] free beta-human chorionic gonadotropin [b-hCG] unconjugated estriol [uE3]) and preterm birth and to create predictive models for preterm birth.

METHODS: Secondary analysis on a prospective database of pregnancies undergoing second-trimester screen with complete follow-up. The multiples of medians (MoM) of the biomarkers were compared between the group of term, preterm (< 37 weeks), early preterm (< 34 weeks), and very early preterm (< 32 weeks) delivery. Predictive models were developed based on adjusted MoMs and logistic regression and diagnostic performances in predicting preterm birth were determined.

RESULTS: Of 20,780 pregnancies, 1,554 (7.5), 363 (1.7), and 158 (0.8%) had preterm, early preterm, and very early preterm birth respectively. High levels of AFP and b-hCG but low levels of uE3 were significantly associated with higher rates of preterm, early preterm and very early preterm delivery. The predictive models had diagnostic performance in predicting preterm birth with the areas under the ROC curve of 0.688, 0.534, 0.599, and 0.718 for AFP, b-hCG, uE3, and combined biomarkers respectively.

CONCLUSION: The second trimester Down syndrome screening could also be used as a tool of risk identification of preterm birth in the same test, without extra-effort and extra-cost.

© 2019 S. Karger AG, Basel.

KEYWORDS: Alpha-fetoprotein; Beta-human chorionic gonadotropin; Early preterm delivery; Preterm delivery; Second trimester screening; Unconjugated estriol PMID: 30602167 DOI: 10.1159/000495614


The Cerebrospinal Fluid Inflammatory Response to Preterm Birth

Front Physiol. 2018 Sep 12;9:1299. doi: 10.3389/fphys.2018.01299. eCollection 2018. Boardman JP1,2, Ireland G1, Sullivan G1, Pataky R1, Fleiss B3,4,5, Gressens P3,4,5, Miron V1.

Background: Preterm birth is the leading risk factor for perinatal white matter injury, which can lead to motor and neuropsychiatric impairment across the life course. There is an unmet clinical need for therapeutics. White matter injury is associated with an altered inflammatory response in the brain, primarily led by microglia, and subsequent hypomyelination. However, microglia can release both damaging and trophic factors in response to injury, and a comprehensive assessment of these factors in the preterm central nervous system (CNS) has not been carried out. Method: A custom antibody array was used to assess relative levels of 50 inflammation- and myelination-associated proteins in the cerebrospinal fluid (CSF) of preterm infants in comparison to term controls. Results: Fifteen proteins differed between the groups: BDNF, BTC, C5a, FasL, Follistatin, IL-1β, IL-2, IL-4, IL-9, IL-17A, MIP-1α, MMP8, SPP1, TGFβ, and TNFβ (p < 0.05). To investigate the temporal regulation of these proteins after injury, we mined a gene expression dataset of microglia isolated from a mouse model of developmental white matter injury. Microglia in the experimental model showed dynamic temporal expression of genes encoding these proteins, with an initial and sustained pro-inflammatory response followed by a delayed anti-inflammatory response, and a continuous expression of genes predicted to inhibit healthy myelination. Conclusion: Preterm CSF shows a distinct neuroinflammatory profile compared to term controls, suggestive of a complex neural environment with concurrent damaging and reparative signals. We propose that limitation of pro-inflammatory responses, which occur early after perinatal insult, may prevent expression of myelination-suppressive genes and support healthy white matter development.

KEYWORDS: brain injury; cerebrospinal fluid; inflammation; microglia; myelination; preterm birth PMID: 30258368 PMCID: PMC6144928 DOI: 10.3389/fphys.2018.01299

Longitudinal assessment of lung function in extremely prematurely born children

Pediatr Pulmonol. 2018 Jan 9. doi: 10.1002/ppul.23933.

Lo J1, Zivanovic S2,3, Lunt A2,3, Alcazar-Paris M2,3, Andradi G2,3, Thomas M4, Marlow N5, Calvert S6, Peacock J7,8, Greenough A2,3,8.


OBJECTIVES: To assess longitudinally small airway function in children born extremely prematurely and whether there was a correlation between airway function in infancy and at 11-14 years. WORKING HYPOTHESES: There would be tracking of airways obstruction and small airway function would deteriorate during childhood in those born extremely prematurely. STUDY DESIGN: A longitudinal study. PATIENT-SUBJECT SELECTION: Thirty-five children with a mean gestational age of 26 weeks had lung function assessed at 1 year corrected and 11-14 years of age. METHODOLOGY: Lung volumes were measured by helium gas dilution (FRCHe ) and plethysmography (FRCpleth ) and small airway function assessed by calculating the FRCHe :FRCpleth ratio. Airway function was assessed at 1 year corrected by measurement of airway resistance (Raw ) and at 11-14 years by assessment of Raw , forced expiratory flow from 75% of vital capacity (FEF75 ), and forced expiratory volume at one second (FEV1 ). RESULTS: At the first assessment, the children had a mean (SD) FRCHe :FRCpleth of 0.90 (0.13) and at the second, 0.83 (0.12) (P = 0.035). There was a significant 0.54% decrease (95%CI: -1.02%, -0.06%) in FRCHe :FRCpleth for increased age per year after adjusting for birth weight, gestational age, sex, and bronchopulmonary dysplasia (P = 0.027). There were significant correlations between Raw at the first assessment and Raw (P = 0.012), FEF75 (P = 0.034), and FEV1 (P = 0.04) at 11-14 years. CONCLUSIONS: These results demonstrate in those born extremely prematurely there is tracking of airway function during childhood. © 2018 Wiley Periodicals, Inc. KEYWORDS: airway function; extreme prematurity; lung volume; small airway function

PMID: 29316378 DOI: 10.1002/ppul.23933


Comparison of cortical folding measures for evaluation of developing human brain

Neuroimage. 2016 Jan 15;125:780-90. doi: 10.1016/j.neuroimage.2015.11.001. Epub 2015 Nov 6.

Shimony JS1, Smyser CD2, Wideman G3, Alexopoulos D4, Hill J5, Harwell J6, Dierker D7, Van Essen DC8, Inder TE9, Neil JJ10.


We evaluated 22 measures of cortical folding, 20 derived from local curvature (curvature-based measures) and two based on other features (sulcal depth and gyrification index), for their capacity to distinguish between normal and aberrant cortical development. Cortical surfaces were reconstructed from 12 term-born control and 63 prematurely-born infants. Preterm infants underwent 2-4 MR imaging sessions between 27 and 42weeks postmenstrual age (PMA). Term infants underwent a single MR imaging session during the first postnatal week. Preterm infants were divided into two groups. One group (38 infants) had no/minimal abnormalities on qualitative assessment of conventional MR images. The second group (25 infants) consisted of infants with injury on conventional MRI at term equivalent PMA. For both preterm infant groups, all folding measures increased or decreased monotonically with increasing PMA, but only sulcal depth and gyrification index differentiated preterm infants with brain injury from those without. We also compared scans obtained at term equivalent PMA (36-42weeks) for all three groups. No curvature-based measured distinguished between the groups, whereas sulcal depth distinguished term control from injured preterm infants and gyrification index distinguished all three groups. When incorporating total cerebral volume into the statistical model, sulcal depth no longer distinguished between the groups, though gyrification index distinguished between all three groups and positive shape index distinguished between the term control and uninjured preterm groups. We also analyzed folding measures averaged over brain lobes separately. These results demonstrated similar patterns to those obtained from the whole brain analyses. Overall, though the curvature-based measures changed during this period of rapid cerebral development, they were not sensitive for detecting the differences in folding associated with brain injury and/or preterm birth. In contrast, gyrification index was effective in differentiating these groups. Copyright © 2015 Elsevier Inc. All rights reserved. KEYWORDS: Brain injury; Cortical curvature; Cortical folding; Premature infant

PMID 26550941

Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of Women at Risk of Imminent Preterm Birth: A Systematic Review and Meta-Analysis

PLoS One. 2016 Feb 3;11(2):e0147604. doi: 10.1371/journal.pone.0147604.

Amiya RM1,2, Mlunde LB3, Ota E1, Swa T4, Oladapo OT5, Mori R1.


BACKGROUND: This study synthesizes available evidence on antenatal corticosteroids (ACS) use among special subgroups of women at risk of imminent preterm birth, including those (1) with pregestational and gestational diabetes mellitus, (2) undergoing elective caesarean section (CS) in late preterm (34 to<37 weeks), (3) with chorioamnionitis, and (4) with growth-restricted fetuses. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Library, POPLINE, and World Health Organization Regional Databases was conducted for all comparative studies. Two reviewers independently determined study eligibility, extracted data, and assessed study quality. Pooled mean differences and odds ratios with 95% confidence intervals were estimated from available data, based on fixed- and random-effects models, as appropriate. RESULTS: No eligible studies were identified for ACS use in diabetic pregnant women or those undergoing elective CS at late preterm. Nine studies each on ACS use in women with chorioamnionitis and in women with fetal growth restriction met inclusion criteria; eight studies were separately included in the meta-analyses for the two subpopulations. For ACS administration in women with chorioamnionitis, pooled analyses showed reductions in neonatal mortality (OR: 0.49, 95% CI: 0.34-0.73), respiratory distress syndrome (OR: 0.58, 95% CI: 0.44-0.76), intraventricular haemorrhage (OR: 0.41, 95% CI: 0.24-0.69), and severe intraventricular haemorrhage (OR: 0.40, 95% CI: 0.24-0.69). Maternal and long-term newborn outcomes were not reported. Effects of ACS use were inconclusive for cases with fetal growth restriction. CONCLUSION: Direct evidence on the effectiveness and safety of ACS is lacking for diabetic pregnant women at risk of preterm birth and those undergoing elective late-preterm CS, though this does not necessarily recommend against their use in diabetic women. While evidence remains inconclusive for women with growth-restricted preterm neonates, ACS appears to benefit preterm neonates delivered by women with chorioamnionitis. High-quality studies on maternal and long-term child outcomes in more diverse settings are needed to establish the balance of potential harms versus benefits in using ACS for these understudied subgroups.

PMID 26841022


Outcomes for extremely premature infants

Anesth Analg. 2015 Jun;120(6):1337-51. doi: 10.1213/ANE.0000000000000705.

Glass HC1, Costarino AT, Stayer SA, Brett CM, Cladis F, Davis PJ.


Premature birth is a significant cause of infant and child morbidity and mortality. In the United States, the premature birth rate, which had steadily increased during the 1990s and early 2000s, has decreased annually for 7 years and is now approximately 11.39%. Human viability, defined as gestational age at which the chance of survival is 50%, is currently approximately 23 to 24 weeks in developed countries. Infant girls, on average, have better outcomes than infant boys. A relatively uncomplicated course in the intensive care nursery for an extremely premature infant results in a discharge date close to the prenatal estimated date of confinement. Despite technological advances and efforts of child health experts during the last generation, the extremely premature infant (less than 28 weeks gestation) and extremely low birth weight infant (<1000 g) remain at high risk for death and disability with 30% to 50% mortality and, in survivors, at least 20% to 50% risk of morbidity. The introduction of continuous positive airway pressure, mechanical ventilation, and exogenous surfactant increased survival and spurred the development of neonatal intensive care in the 1970s through the early 1990s. Routine administration of antenatal steroids during premature labor improved neonatal mortality and morbidity in the late 1990s. The recognition that chronic postnatal administration of steroids to infants should be avoided may have improved outcomes in the early 2000s. Evidence from recent trials attempting to define the appropriate target for oxygen saturation in preterm infants suggests arterial oxygen saturation between 91% and 95% (compared with 85%-89%) avoids excess mortality; however, final analyses of data from these trials have not been published, so definitive recommendations are still pending. The development of neonatal neurocritical intensive care units may improve neurocognitive outcomes in this high-risk group. Long-term follow-up to detect and address developmental, learning, behavioral, and social problems is critical for children born at these early gestational ages.The striking similarities in response to extreme prematurity in the lung and brain imply that agents and techniques that benefit one organ are likely to also benefit the other. Finally, because therapy and supportive care continue to change, the outcomes of extremely low birth weight infants are ever evolving. Efforts to minimize injury, preserve growth, and identify interventions focused on antioxidant and anti-inflammatory pathways are now being evaluated. Thus, treating and preventing long-term deficits must be developed in the context of a "moving target."

PMID 25988638

Cortical structural abnormalities in very preterm children at 7years of age

Neuroimage. 2015 Apr 1;109:469-79. doi: 10.1016/j.neuroimage.2015.01.005. Epub 2015 Jan 20.

Zhang Y1, Inder TE2, Neil JJ3, Dierker DL4, Alexopoulos D5, Anderson PJ6, Van Essen DC7.


We analyzed long-lasting alterations in brain morphometry associated with preterm birth using volumetric and surface-based analyses applied to children at age 7years. Comparison of 24 children born very preterm (VPT) to 24 healthy term-born children revealed reductions in total cortical gray matter volume, white matter volume, cortical surface area and gyrification index. Regional cortical shape abnormalities in VPT children included the following: shallower anterior superior temporal sulci, smaller relative surface area in the inferior sensori-motor cortex and posterior superior temporal cortex, larger relative surface area and a cingulate sulcus that was shorter or more interrupted in medial frontoparietal cortex. These findings indicate a complex pattern of regional vulnerabilities in brain development that may contribute to the diverse and long-lasting neurobehavioral consequences that can occur after very premature birth. Copyright © 2015 Elsevier Inc. All rights reserved. KEYWORDS: Cortical surface; Folding; MRI; Relative surface area; Structural abnormality; Very preterm; Volume

PMID 25614973


A Comparison of the Short-term Morbidity and Mortality Between Late Preterm and Term Newborns

Ann Acad Med Singapore. 2014 Jul;43(7):346-54.

Tan JH1, Poon WB, Lian WB, Ho SK.


INTRODUCTION: Late preterm babies are defined as those born between 34 to 36 completed weeks. There has been a recent increased awareness that this group of babies has a higher incidence of morbidity as compared to term babies. The aim of this study was to evaluate the short-term morbidities occurring in this group of babies managed in the neonatal unit at Singapore General Hospital (SGH). MATERIALS AND METHODS: A retrospective study was done of babies managed in the neonatal unit at SGH from January 2005 to December 2008. Maternal, perinatal and neonatal data were obtained from the departmental database. The outcomes of late preterm infants were compared with term infants. RESULTS: A total of 6826 babies were admitted. Ten percent (681 out of 6826) of babies were late preterm babies, making up 63% (681 out of 1081) of all preterm babies. Late preterm babies had significantly greater need for resuscitation at birth. They also had statistically significant increased risks of developing hyaline membrane disease (2.5% vs 0.1%), transient tachypnoea of the newborn (TTN) (8.1% vs 1.7%), pneumonia (7.0% vs 2.8%), patent ductus arteriosus (PDA) (4.3% vs 1.1%), hypotension (0.7% vs 0%), apnoea (3.7% vs 0%), gastrointestinal (GI) bleeding (1.5% vs 0.3%), polycythaemia (2.2% vs 1.0%), anaemia (3.4% vs 1.2%), thrombocytopenia (3.2% vs 0.6%), hypoglycaemia (6.6% vs 1.7%), neonatal jaundice requiring phototherapy (41.1% vs 12.2%) and sepsis (1.7% vs 0.6%). CONCLUSION: Late preterm infants are indeed a vulnerable group of infants with significant morbidities that need to be addressed and treated. Despite their relatively large size and being almost term, the understanding that late preterm infants are not similar to term infants is important to both obstetricians and neonatologists. PMID 25142470

Placental Transfusion Strategies in Very Preterm Neonates: A Systematic Review and Meta-analysis

Obstet Gynecol. 2014 Jun 4. [Epub ahead of print]

Backes CH1, Rivera BK, Haque U, Bridge JA, Smith CV, Hutchon DJ, Mercer JS.


OBJECTIVE:: To investigate the effects of interventions promoting placental transfusion at delivery (delayed cord clamping or umbilical cord milking) compared with early cord clamping on outcomes among premature neonates of less than 32 weeks of gestation. DATA SOURCES:: A systematic search was conducted of PubMed, Embase, and databases (January 1965 to December 2013) for articles relating to placental transfusion strategies in very preterm neonates. METHODS OF STUDY SELECTION:: Literature searches returned 369 articles with 82 considered in full. We only included data from studies with an average gestational age of less than 32 weeks of gestation enrolled in randomized trials of enhanced placental-fetal transfusion interventions (delayed cord clamping or umbilical cord milking) compared with early cord clamping. TABULATION, INTEGRATION, AND RESULTS:: We identified 12 eligible studies describing a total of 531 neonates with an average gestation of 28 weeks. Benefits of greater placental transfusion were decreased mortality (eight studies, risk ratio 0.42, 95% confidence interval [CI] 0.19-0.95, 3.4% compared with 9.3%, P=.04), lower incidence of blood transfusions (six studies, risk ratio 0.75, 95% CI 0.63-0.92, 49.3% compared with 66%, P<.01), and lower incidence of intraventricular hemorrhage (nine studies, risk ratio 0.62, 95% CI 0.43-0.91, 16.7% compared with 27.3%, P=.01). There was a weighted mean difference of -1.14 blood transfusions (six studies, 95% CI -2.01-0.27, P<.01) and a 3.24-mmHg increase in blood pressure at 4 hours of life (four studies, 95% CI 1.76-4.72, P<.01). No differences were observed between the groups across all available safety measures (5-minute Apgar scores, admission temperature, incidence of delivery room intubation, peak serum bilirubin levels). CONCLUSIONS:: Results of this meta-analysis suggest that enhanced placental transfusion (delayed umbilical cord clamping or umbilical cord milking) at birth provides better neonatal outcomes than does early cord clamping, most notably reductions in overall mortality, lower risk of intraventricular hemorrhage, and decreased blood transfusion incidence. The optimal umbilical cord clamping practice among neonates requiring immediate resuscitation remains uncertain.

PMID 24901269


Evaluation of a quantitative fetal fibronectin test for spontaneous preterm birth in symptomatic women

Am J Obstet Gynecol. 2013 Feb;208(2):122.e1-6. doi: 10.1016/j.ajog.2012.10.890. Epub 2012 Nov 16.

Abbott DS1, Radford SK, Seed PT, Tribe RM, Shennan AH.


OBJECTIVE: The purpose of this study was to determine whether quantification of cervicovaginal fluid fetal fibronectin (fFN) improves diagnostic accuracy of spontaneous preterm birth (sPTB) in symptomatic women. STUDY DESIGN: A prospective blinded predefined secondary analysis of a larger study of cervicovaginal fluid fFN concentration (nanograms per milliliter) in women symptomatic of preterm labor (n =300 women; 22-35 weeks' gestation) with a Hologic 10Q system (Hologic, Marlborough, MA). Clinicians were blinded to the result until after the delivery, but the qualitative Hologic TLI(IQ) fFN result was made available. RESULTS: The positive predictive value for sPTB (<34 weeks' gestation) increased from 19%, 32%, 61%, and 75% with increasing thresholds (10, 50, 200, and 500 ng/mL, respectively). Compared with <10 ng/mL fFN, the relative risk of delivery was 5.6 (95% confidence interval [CI], 1.05-29.57), 7.9 (95% CI, 1.38-45.0), 22.8 (95% CI, 3.84-135.5), and 51.3 (95% CI, 12.49-211.2; P < .01). CONCLUSION: Quantitative fFN provides thresholds (10 and 200 ng/mL) in addition to the qualitative method (50 ng/mL) to discriminate the risk of sPTB in symptomatic women. Copyright © 2013 Mosby, Inc. All rights reserved.

PMID 23164760

Fetal and Maternal Genes' Influence on Gestational Age in a Quantitative Genetic Analysis of 244,000 Swedish Births

Am J Epidemiol. 2013 Apr 7. [Epub ahead of print]

York TP, Eaves LJ, Lichtenstein P, Neale MC, Svensson A, Latendresse S, Långström N, Strauss JF 3rd.


Although there is increasing evidence that genetic factors influence gestational age, it is unclear to what extent this is due to fetal and/or maternal genes. In this study, we apply a novel analytical model to estimate genetic and environmental contributions to pregnancy history records obtained from 165,952 Swedish families consisting of offspring of twins, full siblings, and half-siblings (1987-2008). Results indicated that fetal genetic factors explained 13.1% (95% confidence interval (CI): 6.8, 19.4) of the variation in gestational age at delivery, while maternal genetic factors accounted for 20.6% (95% CI: 18.1, 23.2). The largest contribution to differences in the timing of birth were environmental factors, of which 10.1% (95% CI: 7.0, 13.2) was due to factors shared by births of the same mother, and 56.2% (95% CI: 53.0, 59.4) was pregnancy specific. Similar models fit to the same data dichotomized at clinically meaningful thresholds (e.g., preterm birth) resulted in less stable parameter estimates, but the collective results supported a model of homogeneous genetic and environmental effects across the range of gestational age. Since environmental factors explained most differences in the timing of birth, genetic studies may benefit from understanding the specific effect of fetal and maternal genes in the context of these yet-unidentified factors.

PMID 23568591

Elevated Soluble Triggering Receptor Expressed on Myeloid Cells (sTREM)-1 Levels in Maternal Serum during Term and Preterm Labor

PLoS One. 2013;8(2):e56050. doi: 10.1371/journal.pone.0056050. Epub 2013 Feb 28.

Tency I, Verstraelen H, Saerens B, Verhasselt B, Vaneechoutte M, Degomme O, Verhelst R, Temmerman M. Source Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.


BACKGROUND: Infection and inflammation are important mechanisms leading to preterm birth. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) belongs to a family of cell surface receptors that seems to play an important role in fine-tuning the immune response. It has been demonstrated that sTREM-1 is involved in bacterial infection as well as in non-infectious inflammatory conditions. Few studies have investigated serum sTREM-1 expression during preterm labor. Therefore, the purpose of this study was to assess sTREM-1 concentrations in maternal serum during term and preterm labor. METHODS: This case control study included 176 singleton pregnancies in the following groups: patients in (1) preterm labor, delivered before 34 weeks () (n = 52); (2) , not in labor, matched for gestational age (GA) with the PTB group (n = 52); (3) (n = 40) and (4) (n = 32). sTREM-1 concentrations were determined by enzyme-linked immunoassay. RESULTS: sTREM-1 was detected in all serum samples. Median sTREM-1 concentrations were significantly higher in women with vs. (367 pg/ml, interquartile range (IQR) 304-483 vs. 273 pg/ml, IQR 208-334; P<0.001) and in women vs. (300 pg/ml, IQR 239-353 vs. 228 pg/ml, IQR 174-285; P<0.001). Women with had significantly higher levels of sTREM-1 compared to women (P = 0.004). Multiple regression analysis, with groups recoded as three key covariates (labor, preterm and rupture of the membranes), showed significantly higher sTREM-1 concentrations for labor (+30%, P<0.001) and preterm (+15%, P = 0.005) after adjusting for educational level, history of PTB and sample age. CONCLUSIONS: sTREM-1 concentrations in maternal serum were elevated during spontaneous term and preterm labor and sTREM-1 levels were significantly higher in preterm labor.

PMID 23468854

Adolescent pregnancy outcomes in the province of ontario: a cohort study

J Obstet Gynaecol Can. 2013 Mar;35(3):234-45.

Fleming N, Ng N, Osborne C, Biederman S, Yasseen AS 3rd, Dy J, Rennicks White R, Walker M. Source Department of Obstetrics and Gynecology and Newborn Care, Faculty of Medicine, University of Ottawa, Ottawa ON, Department of Surgery, The Children's Hospital of Eastern Ontario, The University of Ottawa, Ottawa ON.


Objective: Few Canadian studies have examined the association between adolescent pregnancy and adverse pregnancy outcomes. The objective of this cohort study was to characterize the association between adolescent pregnancy and specific adverse maternal, obstetrical, and neonatal outcomes, as well as maternal health behaviours. Methods: We conducted a retrospective population-based cohort study of all singleton births in Ontario between January 2006 and December 2010, using the Better Outcomes Registry and Network database. Outcomes for pregnant women < 20 years of age (adolescent) were compared with those of women 20 to 35 years old (adult). Results: This study included 551 079 singleton birth records, 23 992 (4.35%) of which derived from adolescent pregnancies. Adolescents had a higher rate of smoking and substance use than adult women and were within the lowest education and family income quintiles. Adolescents had a significantly lower risk of gestational hypertension (adjusted relative risk [aRR] 0.73) and gestational diabetes (aRR 0.34), placental abruption (aRR 0.80), and placenta previa (aRR 0.36), but their risk of preterm premature rupture of membranes was significantly higher (RR 1.16). Adolescents had a significantly higher proportion of spontaneous vaginal delivery (aRR 1.76), significantly lower rates of use of epidural analgesia (aRR 0.93), of Caesarean section (aRR 0.57), and of assisted vaginal delivery (aRR 0.76), but a significantly higher risk of emergency CS (aRR 1.31). Neonates with an adolescent mother had significantly higher risks of admission to NICU (aRR 1.08) and very preterm birth (aRR 1.16). There was no significant difference between the two groups in rates of small for gestational age babies, low birth weight, preterm birth, and fetal death. Adolescents had significantly lower rates of prenatal class attendance, prenatal visits in the first trimester, and breastfeeding. Conclusion: This large Canadian cohort study confirms that, compared with adults, adolescents have improved outcomes such as lower rates of gestational hypertension, gestational diabetes, antepartum hemorrhage, and operative deliveries. However, adolescents also have higher sociodemographic risk factors and seek prenatal care later than adults. These risk factors in combination with young age, lead to other important maternal, obstetrical, and neonatal adverse outcomes. These findings highlight the importance of multidisciplinary prenatal management in the adolescent population to address their high-risk needs, to ensure healthy pregnancies, and to reduce adverse perinatal outcomes.

PMID 23470111


Singleton preterm birth: risk factors and association with assisted reproductive technology

Matern Child Health J. 2012 May;16(4):807-13. doi: 10.1007/s10995-011-0787-8.

Tepper NK, Farr SL, Cohen BB, Nannini A, Zhang Z, Anderson JE, Jamieson DJ, Macaluso M. Source National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.


The objectives of this study were to determine risk factors for early (less than 34 weeks gestation) and late (34-36 weeks gestation) preterm singleton birth, by assisted reproductive technology (ART) status. We linked data from Massachusetts birth records and ART records representing singleton live births from 1997 through 2004. Using multinomial regression models, we assessed risk factors for early and late preterm birth by ART status. From 1997 to 2004 in Massachusetts, among non-ART births, risk factors for early and late preterm birth were similar and included women <15 and ≥ 35 years of age, those of non-white race or Hispanic ethnicity, those with ≤ 12 years of education, those with chronic diabetes, those with gestational diabetes, those with gestational hypertension, those who smoked during pregnancy, those who used fertility medications, and those who had not had a previous live birth. Among ART births, risk factors for early and late preterm birth differed and odds of early preterm birth were increased among women with ≤ 12 years of education while odds of late preterm birth were increased among women with gestational diabetes. Odds of both early and late preterm birth were increased among women of non-white race or Hispanic ethnicity and among women with gestational hypertension. Among non-ART births, increased risk for preterm birth was more strongly related to socioeconomic factors than among ART births. Medical conditions were associated with an increased risk for preterm birth regardless of women's ART status. Efforts to prevent preterm births should focus on reducing modifiable risk factors.

PMID 21516300

Prepregnancy maternal body mass index and preterm delivery

Am J Obstet Gynecol. 2012 Sep;207(3):212.e1-7. doi: 10.1016/j.ajog.2012.06.002. Epub 2012 Jun 11.

Khatibi A, Brantsaeter AL, Sengpiel V, Kacerovsky M, Magnus P, Morken NH, Myhre R, Gunnes N, Jacobsson B. Source Department of Obstetrics and Gynecology, Sahlgrenska University Hospital/East, Gothenburg, Sweden.


OBJECTIVE: The purpose of this study was to determine the influence of maternal prepregnancy body mass index on preterm delivery (PTD), controlling for health and lifestyle variables. STUDY DESIGN: Prospective data were from 83,544 pregnancies in the Norwegian Mother and Child Cohort Study. PTD was divided into early PTD (22 + 0 to 31 + 6 weeks' gestation) and late PTD (32 + 0 to 36 + 6 weeks' gestation). RESULTS: The overall prevalence of PTD was 5.1%. Increased body mass index was associated with an increased risk of PTD; adjusted odds ratio (aOR) ranged from 1.11 (95% confidence interval [CI], 1.03-1.20) for preobesity to 2.00 (95% CI, 1.48-2.71) for grade-III obesity in the group that included all PTD subgroups. Grade-III obese women had an increased risk of both early and late PTD: aOR, 3.24 (95% CI, 1.71-6.14) and 1.81 (95% CI, 1.29-2.54), respectively. CONCLUSION: Prepregnancy maternal overweight increases the risk of both early and late PTD. Copyright © 2012 Mosby, Inc. All rights reserved.

PMID 22835494

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Academic Achievement Varies With Gestational Age Among Children Born at Term

Pediatrics. 2012 Jul 2. [Epub ahead of print]

Noble KG, Fifer WP, Rauh VA, Nomura Y, Andrews HF. Source Departments of Pediatrics.


OBJECTIVE: The goal of this study was to examine the degree to which children born within the "normal term" range of 37 to 41 weeks' gestation vary in terms of school achievement. METHODS: This study analyzed data from 128 050 singleton births born between 37 and 41 weeks' gestation in a large US city. Data were extracted from city birth records to assess a number of obstetric, social, and economic variables, at both the individual and community levels. Birth data were then matched with public school records of standardized city-wide third-grade reading and math tests. Specifically, we assessed (1) whether children born within the normal term range of 37 to 41 weeks' gestation show differences in reading and/or math ability 8 years later as a function of gestational age, and (2) the degree to which a wide range of individual- and community-level social and biological factors mediate this effect. RESULTS: Analyses revealed that gestational age within the normal term range was significantly and positively related to reading and math scores in third grade, with achievement scores for children born at 37 and 38 weeks significantly lower than those for children born at 39, 40, or 41 weeks. This effect was independent of birth weight, as well as a number of other obstetric, social, and economic factors. CONCLUSIONS: Earlier normal term birth may be a characteristic considered by researchers, clinicians, and parents to help identify children who may be at risk for poorer school performance.

PMID 22753563

Preterm Birth and Psychiatric Disorders in Young Adult Life

Arch Gen Psychiatry. 2012 Jun 1:610-617. doi: 10.1001/archgenpsychiatry.2011.1374. [Epub ahead of print]

Nosarti C, Reichenberg A, Murray RM, Cnattingius S, Lambe MP, Yin L, Maccabe J, Rifkin L, Hultman CM.


CONTEXT Preterm birth, intrauterine growth restriction, and delivery-related hypoxia have been associated with schizophrenia. It is unclear whether these associations pertain to other adult-onset psychiatric disorders and whether these perinatal events are independent. OBJECTIVE To investigate the relationships among gestational age, nonoptimal fetal growth, Apgar score, and various psychiatric disorders in young adult life. DESIGN Historical population-based cohort study. SETTING Identification of adult-onset psychiatric admissions using data from the National Board of Health and Welfare, Stockholm, Sweden. PARTICIPANTS All live-born individuals registered in the nationwide Swedish Medical Birth Register between 1973 and 1985 and living in Sweden at age 16 years by December 2002 (n = 1 301 522). MAIN OUTCOME MEASURES Psychiatric hospitalization with nonaffective psychosis, bipolar affective disorder, depressive disorder, eating disorder, drug dependency, or alcohol dependency, diagnosed according to the International Classification of Diseases codes for 8 through 10. Cox proportional hazards regression models were used to estimate hazard ratios and 95% CIs. RESULTS Preterm birth was significantly associated with increased risk of psychiatric hospitalization in adulthood (defined as ≥16 years of age) in a monotonic manner across a range of psychiatric disorders. Compared with term births (37-41 weeks), those born at 32 to 36 weeks' gestation were 1.6 (95% CI, 1.1-2.3) times more likely to have nonaffective psychosis, 1.3 (95% CI, 1.1-1.7) times more likely to have depressive disorder, and 2.7 (95% CI, 1.6-4.5) times more likely to have bipolar affective disorder. Those born at less than 32 weeks' gestation were 2.5 (95% CI, 1.0-6.0) times more likely to have nonaffective psychosis, 2.9 (95% CI, 1.8-4.6) times more likely to have depressive disorder, and 7.4 (95% CI, 2.7-20.6) times more likely to have bipolar affective disorder. CONCLUSIONS The vulnerability for hospitalization with a range of psychiatric diagnoses may increase with younger gestational age. Similar associations were not observed for nonoptimal fetal growth and low Apgar score.

PMID 22660967

Antenatal magnesium sulfate and neuroprotection

Curr Opin Pediatr. 2012 Apr;24(2):154-9.

Doyle LW. Source Murdoch Childrens Research Institute, The Royal Women's Hospital, University of Melbourne, Melbourne, Victoria, Australia.


PURPOSE OF REVIEW: Antenatal magnesium sulfate may reduce the excessive rates of cerebral palsy in survivors of very preterm birth. RECENT FINDINGS: There are five randomized controlled trials of magnesium sulfate therapy given to the mother prior to very preterm birth which have reported neurological outcomes for the child, in four of which the primary aim of the trial was neuroprotection for the fetus. From meta-analysis of these randomized trials, the rate of cerebral palsy was reduced by magnesium sulfate [relative risk (RR) = 0.69; 95% confidence interval (CI) = 0.54-0.87; five trials; 6145 infants). Magnesium sulfate also lowered the rate of substantial motor dysfunction in early childhood (RR = 0.61; 95% CI = 0.44-0.85; four trials; 5980 infants). In addition, where the main aim of the trial was neuroprotection of the fetus, the rates of the combined outcomes of death or cerebral palsy (RR = 0.86; 95% CI = 0.74-0.98; four trials; 4446 infants) and death or substantial motor dysfunction (RR = 0.85; 95% CI = 0.73-0.98; three trials; 4387 infants) were significantly lower with magnesium. SUMMARY: On the basis of these findings several countries have now released clinical practice guidelines recommending antenatal magnesium sulfate prior to very preterm birth.

PMID 22227787

Chloride Balance in Preterm Infants during the First Week of Life

Int J Pediatr. 2012;2012:931597. Epub 2012 Mar 8.

Iacobelli S, Kermorvant-Duchemin E, Bonsante F, Lapillonne A, Gouyon JB. Source Neonatology and NICU, GHSR, CHR, BP 350, 97448 Saint Pierre Cedex, Réunion, France.


Objective. To describe the chloride balance in infants born 25-32-week gestation, analyze the association of chloride changes with hydroelectrolytic status and their relationship with perinatal conditions, morbidities, and neurological outcome. Methods. For 7 days after birth, sodium and chloride balance, plasma potassium, phosphate, and total carbon dioxide (tCO(2)) were prospectively determined and strong ion difference (SID) calculated. Three multivariate regression analyses were performed to identify factors associated with high plasma chloride concentration, low SID, and low tCO(2). Results. 107 infants were studied. Plasma chloride concentration was significantly positively associated with plasma sodium concentration. Higher plasma chloride and lower SID were significantly associated with lower plasma tCO(2). Chloride intake was the main independent factor associated with high plasma chloride, low SID, and low plasma tCO(2), with lesser contribution of sodium intake and low gestational age (GA). Also, patent ductus arteriosus and birth weight loss were independent factors affecting plasma chloride and SID. Neither high chloride levels nor low SID were associated to impaired neurological outcome. Conclusions. In preterm infants, chloride balance is influenced by GA and by interrelationship between sodium and chloride intake. High chloride levels are associated with metabolic acidosis but not related to increased risk of impaired neurological outcome.

PMID 22505945

Transvaginal sonographic evaluation of the cervix in asymptomatic singleton pregnancy and management options in short cervix

J Pregnancy. 2012;2012:201628. Epub 2012 Feb 22. Arisoy R, Yayla M. Source Department of Obstetrics and Gynaecology, Gole State Hospital, 34660 Ardahan, Turkey.


Preterm delivery (PTD), defined as birth before 37 completed weeks of gestation, is the leading cause of perinatal morbidity and mortality. Evaluation of the cervical morphology and biometry with transvaginal ultrasonography at 16-24 weeks of gestation is a useful tool to predict the risk of preterm birth in low- and high-risk singleton pregnancies. For instance, a sonographic cervical length (CL) > 30 mm and present cervical gland area have a 96-97% negative predictive value for preterm delivery at <37 weeks. Available evidence supports the use of progesterone to women with cervical length ≤25 mm, irrespective of other risk factors. In women with prior spontaneous PTD with asymptomatic cervical shortening (CL ≤ 25 mm), prophylactic cerclage procedure must be performed and weekly to every two weeks follow-up is essential. This article reviews the evidence in support of the clinical introduction of transvaginal sonography for both the prediction and management of spontaneous preterm labour.

PMID 22523687

Editorial - Prevention and Management of Preterm Birth

Jacquemyn Y, Lamont R, Cornette J, Helmer H. J Pregnancy. 2012;2012:610364. Epub 2012 Mar 18. No abstract available.

Prevention and treatment of preterm delivery is not one of the success stories of modern medicine, preterm birth constitutes the major determinant of perinatal mortality and morbidity, and the long-term results of being born too early often lead to a shorter, less healthy life and a more difficult school and professional career. Different methods have been introduced to predict the advent of preterm labour in asymptomatic women, including fetal fibronectin and transvaginal ultrasound cervical length measurement. R. Arisoy and M. Yayla present data on the evaluation of the cervix in asymptomatic singleton pregnancies; they also address the most frustrating issue: what measures to take once a short cervix has been detected. They restrict their study to singleton pregnancies; although both cervical length and fetal fibronectin are good predictors of preterm delivery in twins, no intervention has proven useful in twins: vaginal progesteron makes no difference and cerclage even worsens the outcome.

Possibilities for real primary prevention are rare and include treatment of asymptomatic bacteriuria and periodontal disease. O. Huck et al. elaborate this last issue and present an excellent overview on both epidemiologic and pathophysiologic data. Another method proposed for primary prevention of preterm birth is the use of progesteron, including vaginal progesteron and systemic 17-hydroxyprogesterone caproate. Starting progesterone treatment can be based not only on cervical length or vaginal fibronectin but also on past obstetrical history. C. E. Ransom et al. comment on the use of 17-hydroxyprogesterone caproate and the influence of obstetric history.

Some newer methods are on the border of being introduced to clinical practice; one such candidate is near-infrared spectroscopy. K. M. Power and colleagues present the use of near-infrared spectroscopy of amniotic fluid to assess preterm delivery.

Once preterm labour has been established, tocolytics are (all too) often used, and what their exact place in treatment is remains open for discussion. Hubinont and F. Debieve present a concise update on tocolysis. In case preterm delivery seems unavoidable, the optimal mode of fetal monitoring and the mode of delivery have to be chosen. Fetal heart rate monitoring in the preterm period constitutes a special challenge and is further commented by K. Afors and E. Chandraharan, while S. R. Bhatta and C. R. Keriakos discuss the optimal way of delivering the preterm baby in vertex position.

As the articles in this issue demonstrate, preterm labour and delivery constitute one of the major challenges of obstetrics in the 21st century. PMID 22550589

WHO Report

The first-ever country-by-country estimate of premature births finds that 15 million babies a year are born preterm - more than one in 10 live births. Although more than 60% of preterm births are in sub-Saharan Africa and south Asia, they are also a problem for some high-income countries, including the USA and Brazil. Both rank among the 10 countries with the highest number of preterm births. In the USA, about 12% of all births are preterm, a percentage far higher than in Europe or other developed countries. ...

The Partnership (PMNCH) - joins the maternal, newborn and child health (MNCH) communities into an alliance of more than 350 members to ensure that all women, infants and children not only remain healthy, but thrive. Born Too Soon: The Global Action Report on Preterm Birth

Effects of gestational age at birth on health outcomes at 3 and 5 years of age: population based cohort study

BMJ. 2012 Mar 1;344:e896. doi: 10.1136/bmj.e896.

Boyle EM, Poulsen G, Field DJ, Kurinczuk JJ, Wolke D, Alfirevic Z, Quigley MA. Source Department of Health Sciences, University of Leicester, Leicester LE1 6TP, UK. Abstract OBJECTIVE: To investigate the burden of later disease associated with moderate/late preterm (32-36 weeks) and early term (37-38 weeks) birth. DESIGN: Secondary analysis of data from the Millennium Cohort Study (MCS). SETTING: Longitudinal study of infants born in the United Kingdom between 2000 and 2002. PARTICIPANTS: 18,818 infants participated in the MCS. Effects of gestational age at birth on health outcomes at 3 (n = 14,273) and 5 years (n = 14,056) of age were analysed. MAIN OUTCOME MEASURES: Growth, hospital admissions, longstanding illness/disability, wheezing/asthma, use of prescribed drugs, and parental rating of their children's health. RESULTS: Measures of general health, hospital admissions, and longstanding illness showed a gradient of increasing risk of poorer outcome with decreasing gestation, suggesting a "dose-response" effect of prematurity. The greatest contribution to disease burden at 3 and 5 years was in children born late/moderate preterm or early term. Population attributable fractions for having at least three hospital admissions between 9 months and 5 years were 5.7% (95% confidence interval 2.0% to 10.0%) for birth at 32-36 weeks and 7.2% (1.4% to 13.6%) for birth at 37-38 weeks, compared with 3.8% (1.3% to 6.5%) for children born very preterm (<32 weeks). Similarly, 2.7% (1.1% to 4.3%), 5.4% (2.4% to 8.6%), and 5.4% (0.7% to 10.5%) of limiting longstanding illness at 5 years were attributed to very preterm birth, moderate/late preterm birth, and early term birth. CONCLUSIONS: These results suggest that health outcomes of moderate/late preterm and early term babies are worse than those of full term babies. Additional research should quantify how much of the effect is due to maternal/fetal complications rather than prematurity itself. Irrespective of the reason for preterm birth, large numbers of these babies present a greater burden on public health services than very preterm babies.

PMID 22381676

Patterns and outcomes of preterm hospital admissions during pregnancy in NSW, 2001-2008

Med J Aust. 2012 Mar 5;196(4):261-5.

Badgery-Parker T, Ford JB, Jenkins MG, Morris JM, Roberts CL. Source Centre for Epidemiology and Research, NSW Ministry of Health, Sydney, NSW, Australia.


OBJECTIVE: To assess the frequency and outcomes of preterm hospital admissions during pregnancy, with a focus on transfers to higher levels of care.

DESIGN: Population-based cohort study using linked population data.

SETTING AND SUBJECTS: Women who were admitted to hospital in weeks 20-36 of pregnancy (preterm) and gave birth to a liveborn singleton infant in New South Wales during 2001-2008.

MAIN OUTCOME MEASURE: Numbers of preterm admissions of pregnant women who were discharged without giving birth, were transferred to higher care, or who gave birth.

RESULTS: 110 439 pregnancies (16.0%) involved at least one preterm admission. After their initial preterm admission, 71.9% of women were discharged, 6.3% were transferred and 21.8% gave birth. Median gestational age at admission was 33 weeks and median time to discharge, transfer or giving birth was 1 day. Most women who were transferred or who gave birth had been admitted for preterm rupture of membranes or preterm labour. Of the women who were admitted or were transferred with suspected preterm labour, only 29% and 38%, respectively, gave birth. Compared with other admitted women, women having a first birth, public patients and those living in areas of low socioeconomic status were more likely to be transferred or to give birth. As gestational age increased, the proportion of women transferred decreased and the proportion giving birth increased. Infants born after maternal transfer had lower gestational age and more adverse outcomes than those born without maternal transfer.

CONCLUSIONS: Preterm hospital admission affects one in six women with singleton pregnancies. Methods that could improve assessment of labour status have a large potential to reduce the burden on maternity services. The increased morbidity for infants born after maternal transfer suggests women with high-risk pregnancies are being appropriately identified.

PMID 22409693


Perinatal morbidity associated with late preterm deliveries compared with deliveries between 37 and 40 weeks of gestation

BJOG. 2011 Nov;118(12):1446-54. doi: 10.1111/j.1471-0528.2011.03045.x. Epub 2011 Aug 22.

Cheng YW, Kaimal AJ, Bruckner TA, Halloran DR, Caughey AB. Source Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, 94143-0132, USA. Erratum in BJOG. 2011 Dec;118(13):1687. Hallaron, D R [corrected to Halloran, D R]. Abstract OBJECTIVE: To estimate the risk of short-term complications in neonates born between 34 and 36 weeks of gestation. DESIGN: This is a retrospective cohort study. SETTING: Deliveries in 2005 in the USA. POPULATION: Singleton live births between 34 and 40 weeks of gestation. METHODS: Gestational age was subgrouped into 34, 35, 36 and 37-40 completed weeks of gestation. Statistical comparisons were performed using chi-square test and multivariable logistic regression models, with 37-40 weeks of gestation designated as referent. MAIN OUTCOME MEASURES: Perinatal morbidities, including 5-minute Apgar scores, hyaline membrane disease, neonatal sepsis/antibiotics use, and admission to the intensive care unit. RESULTS: In all, 175,112 neonates were born between 34 and 36 weeks in 2005. Compared with neonates born between 37 and 40 weeks, neonates born at 34 weeks had higher odds of 5-minute Apgar <7 (adjusted odds ratio [aOR] 5.51, 95% CI 5.16-5.88), hyaline membrane disease (aOR 10.2, 95% CI 9.44-10.9), mechanical ventilation use >6 hours (aOR 9.78, 95% CI 8.99-10.6) and antibiotic use (aOR 9.00, 95% CI 8.43-9.60). Neonates born at 35 weeks were similarly at risk of morbidity, with higher odds of 5-minute Apgar <7 (aOR 3.42, 95% CI 3.23-3.63), surfactant use (aOR 3.74, 95% CI 3.21-4.22), ventilation use >6 hours (aOR 5.53, 95% CI 5.11-5.99) and neonatal intensive-care unit admission (aOR 11.3, 95% CI 11.0-11.7). Neonates born at 36 weeks remain at higher risk of morbidity compared with deliveries at 37-40 weeks of gestation. CONCLUSIONS: Although the risk of undesirable neonatal outcomes decreases with increasing gestational age, the risk of neonatal complications in late preterm births remains higher compared with infants delivered at 37-40 weeks of gestation. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

PMID 21883872

Children's Brain Development Benefits from Longer Gestation

Front Psychol. 2011;2:1. Epub 2011 Feb 9.

Davis EP, Buss C, Muftuler LT, Head K, Hasso A, Wing DA, Hobel C, Sandman CA. Source Women and Children's Health and Well-Being Project, Department of Psychiatry and Human Behavior, University of California Irvine Orange, CA, USA. Abstract Disruptions to brain development associated with shortened gestation place individuals at risk for the development of behavioral and psychological dysfunction throughout the lifespan. The purpose of the present study was to determine if the benefit for brain development conferred by increased gestational length exists on a continuum across the gestational age spectrum among healthy children with a stable neonatal course. Neurodevelopment was evaluated with structural magnetic resonance imaging in 100 healthy right-handed 6- to 10-year-old children born between 28 and 41 gestational weeks with a stable neonatal course. Data indicate that a longer gestational period confers an advantage for neurodevelopment. Longer duration of gestation was associated with region-specific increases in gray matter density. Further, the benefit of longer gestation for brain development was present even when only children born full term were considered. These findings demonstrate that even modest decreases in the duration of gestation can exert profound and lasting effects on neurodevelopment for both term and preterm infants and may contribute to long-term risk for health and disease.

PMID 21713130

The surprising composition of the salivary proteome of preterm human newborn

Saliva is a body fluid of a unique composition devoted to protect the mouth cavity and the digestive tract. A quantitative label-free MS analysis showed protein levels altered in relation to the postconceptional age and suggested coordinate and hierarchical functions for these proteins during development. In summary, this study shows for the first time that analysis of these proteins in saliva of preterm newborns might represent a non-invasive way to obtain precious information of the molecular mechanisms of development of human fetal oral structures.

PMID 20943598


Differing prevalence and diversity of bacterial species in fetal membranes from very preterm and term labor

PLoS One. 2009 Dec 8;4(12):e8205.

Jones HE, Harris KA, Azizia M, Bank L, Carpenter B, Hartley JC, Klein N, Peebles D. Source Infectious Diseases and Microbiology Unit, Institute of Child Health, London, United Kingdom.


BACKGROUND: Intrauterine infection may play a role in preterm delivery due to spontaneous preterm labor (PTL) and preterm prolonged rupture of membranes (PPROM). Because bacteria previously associated with preterm delivery are often difficult to culture, a molecular biology approach was used to identify bacterial DNA in placenta and fetal membranes. METHODOLOGY/PRINCIPAL FINDINGS: We used broad-range 16S rDNA PCR and species-specific, real-time assays to amplify bacterial DNA from fetal membranes and placenta. 74 women were recruited to the following groups: PPROM <32 weeks (n = 26; 11 caesarean); PTL with intact membranes <32 weeks (n = 19; all vaginal birth); indicated preterm delivery <32 weeks (n = 8; all caesarean); term (n = 21; 11 caesarean). 50% (5/10) of term vaginal deliveries were positive for bacterial DNA. However, little spread was observed through tissues and species diversity was restricted. Minimal bacteria were detected in term elective section or indicated preterm deliveries. Bacterial prevalence was significantly increased in samples from PTL with intact membranes [89% (17/19) versus 50% (5/10) in term vaginal delivery p = 0.03] and PPROM (CS) [55% (6/11) versus 0% (0/11) in term elective CS, p = 0.01]. In addition, bacterial spread and diversity was greater in the preterm groups with 68% (13/19) PTL group having 3 or more positive samples and over 60% (12/19) showing two or more bacterial species (versus 20% (2/10) in term vaginal deliveries). Blood monocytes from women with PTL with intact membranes and PPROM who were 16S bacterial positive showed greater level of immune paresis (p = 0.03). A positive PCR result was associated with histological chorioamnionitis in preterm deliveries. CONCLUSION/SIGNIFICANCE: Bacteria are found in both preterm and term fetal membranes. A greater spread and diversity of bacterial species were found in tissues of women who had very preterm births. It is unclear to what extent the greater bacterial prevalence observed in all vaginal delivery groups reflects bacterial contamination or colonization of membranes during labor. Bacteria positive preterm tissues are associated with histological chorioamnionitis and a pronounced maternal immune paresis.

PMID 19997613


The frequency, clinical significance, and pathological features of chronic chorioamnionitis: a lesion associated with spontaneous preterm birth

Mod Pathol. 2010 Jul;23(7):1000-11. doi: 10.1038/modpathol.2010.73. Epub 2010 Mar 26.

Kim CJ1, Romero R, Kusanovic JP, Yoo W, Dong Z, Topping V, Gotsch F, Yoon BH, Chi JG, Kim JS. Author information

Abstract Acute chorioamnionitis is a well-established lesion of the placenta in cases with intra-amniotic infection. In contrast, the clinicopathological significance of chronic chorioamnionitis is unclear. This study was conducted to determine the frequency and severity of chronic chorioamnionitis in normal pregnancy and in various pregnancy complications. Placentas from the following patient groups were studied: (1) term not in labor (n=100), (2) term in labor (n=100), (3) preterm labor (n=100), (4) preterm prelabor rupture of membranes (n=100), (5) preeclampsia at term (n=100), (6) preterm preeclampsia (n=100), and (7) small-for-gestational-age at term (n=100). Amniotic fluid CXCL10 concentration was measured in 64 patients. CXCL9, CXCL10, and CXCL11 mRNA expressions in the chorioamniotic membranes were assessed using real-time quantitative reverse transcription-PCR. The frequency of chronic chorioamnionitis in the preterm labor group and the preterm prelabor rupture of membranes group was 34 and 39%, respectively, which was higher than that of normal-term placentas (term not in labor, 19%; term in labor, 8%; P<0.05 each). The frequency of chronic chorioamnionitis in the preeclampsia at term group, preterm preeclampsia group, and small-for-gestational-age group was 23, 16, and 13%, respectively. Concomitant villitis of unknown etiology was found in 38 and 36% of preterm labor cases and preterm prelabor rupture of membranes cases with chronic chorioamnionitis, respectively. Interestingly, the median gestational age of preterm chronic chorioamnionitis cases was higher than that of acute chorioamnionitis cases (P<0.05). The median amniotic fluid CXCL10 concentration was higher in cases with chronic chorioamnionitis than in those without, in both the preterm labor group and preterm prelabor rupture of membranes group (P<0.05 and P<0.01, respectively). CXCL9, CXCL10, and CXCL11 mRNA expression in the chorioamniotic membranes was also higher in cases with chronic chorioamnionitis than in those without chronic chorioamnionitis (P<0.05). We propose that chronic chorioamnionitis defines a common placental pathological lesion among the preterm labor and preterm prelabor rupture of membranes groups, especially in cases of late preterm birth. Its association with villitis of unknown etiology and the chemokine profile in amniotic fluid suggests an immunological origin, akin to transplantation rejection and graft-versus-host disease in the chorioamniotic membranes.

PMID 20348884

Effects of chorioamnionitis on the feral lung

Clin Perinatol. 2012 Sep;39(3):441-57. doi: 10.1016/j.clp.2012.06.010.

Jobe AH. Author information

Abstract Very preterm infants are commonly exposed to a chronic, often asymptomatic, chorioamnionitis that is diagnosed by histologic evaluation of the placenta only after delivery. The reported effects of these exposures on fetal lungs are inconsistent because exposure to different organisms, durations of exposure, and fetal/maternal responses affect outcomes. In experimental models, chorioamnionitis can both injure and mature the fetal lung and cause immune nodulation. Postnatal care strategies also change how chorioamnionitis relates to clinical outcomes such as bronchopulmonary dysplasia. Copyright © 2012 Elsevier Inc. All rights reserved.

PMID 22954262

Antenatal infection/inflammation and postnatal lung maturation and injury

Respir Res. 2001;2(1):27-32. Epub 2001 Jan 11.

Jobe AH1, Ikegami M. Author information


Chorioamnionitis is frequently associated with preterm deliveries before 30 weeks gestation. Chorioamnionitis correlates both with an increased risk of bronchopulmonary dysplasia and with a decreased risk of respiratory distress syndrome. Both interleukin-1alpha and endotoxin can induce inflammation in the fetal lungs and lung maturation after preterm birth when given by intra-amniotic injection. Inflammation can also result in an arrest of alveolarization, and this lung developmental abnormality is prominent in the lungs of preterm infants that die of bronchopulmonary dysplasia. The mechanisms by which infection/inflammation can have both beneficial and injurious effects on the preterm lung remain to be characterized. PMID 11686862