Abstract:
:Evidence from family and twin-based studies provide strong support for a significant contribution of maternal and fetal genetics to the timing of parturition and spontaneous preterm birth. However, there has been only modest success in the discovery of genes predisposing to preterm birth, despite increasing sophistication of genetic and genomic technology. In contrast, DNA variants associated with other traits/diseases have been identified. For example, there is overwhelming evidence that suggests that the nature and intensity of an inflammatory response in adults and children are under genetic control. Because inflammation is often invoked as an etiologic factor in spontaneous preterm birth, the question of whether spontaneous preterm birth has a genetic predisposition in the case of pathologic inflammation has been of long-standing interest to investigators. Here, we review various genetic approaches used for the discovery of preterm birth genetic variants in the context of inflammation-associated spontaneous preterm birth. Candidate gene studies have sought genetic variants that regulate inflammation in the mother and fetus; however, the promising findings have often not been replicated. Genome-wide association studies, an approach to the identification of chromosomal loci responsible for complex traits, have also not yielded compelling evidence for DNA variants predisposing to preterm birth. A recent genome-wide association study that included a large number of White women (>40,000) revealed that maternal loci contribute to preterm birth. Although none of these loci harbored genes directly related to innate immunity, the results were replicated. Another approach to identify DNA variants predisposing to preterm birth is whole exome sequencing, which examines the DNA sequence of protein-coding regions of the genome. A recent whole exome sequencing study identified rare mutations in genes encoding for proteins involved in the negative regulation (dampening) of the innate immune response (eg, CARD6, CARD8, NLRP10, NLRP12, NOD2, TLR10) and antimicrobial peptide/proteins (eg, DEFB1, MBL2). These findings support the concept that preterm labor, at least in part, has an inflammatory etiology, which can be induced by pathogens (ie, intraamniotic infection) or "danger signals" (alarmins) released during cellular stress or necrosis (ie, sterile intraamniotic inflammation). These findings support the notion that preterm birth has a polygenic basis that involves rare mutations or damaging variants in multiple genes involved in innate immunity and host defense mechanisms against microbes and their noxious products. An overlap among the whole exome sequencing-identified genes and other inflammatory conditions associated with preterm birth, such as periodontal disease and inflammatory bowel disease, was observed, which suggests a shared genetic substrate for these conditions. We propose that whole exome sequencing, as well as whole genome sequencing, is the most promising approach for the identification of functionally significant genetic variants responsible for spontaneous preterm birth, at least in the context of pathologic inflammation. The identification of genes that contribute to preterm birth by whole exome sequencing, or whole genome sequencing, promises to yield valuable population-specific biomarkers to identify the risk for spontaneous preterm birth and potential strategies to mitigate such a risk.
journal_name
Am J Obstet Gynecoljournal_title
American journal of obstetrics and gynecologyauthors
Strauss JF 3rd,Romero R,Gomez-Lopez N,Haymond-Thornburg H,Modi BP,Teves ME,Pearson LN,York TP,Schenkein HAdoi
10.1016/j.ajog.2017.12.009subject
Has Abstractpub_date
2018-03-01 00:00:00pages
294-314.e2issue
3eissn
0002-9378issn
1097-6868pii
S0002-9378(17)32484-5journal_volume
218pub_type
杂志文章,评审abstract:OBJECTIVE:Ovarian vein thrombosis is associated with pregnancy and pelvic surgery. Postpartum ovarian vein thrombosis is associated with infection and a high morbidity rate and is treated with anticoagulant and intravenous antibiotic therapy. The natural history of such thrombotic events after debulking surgery for ova...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2015.02.028
更新日期:2015-08-01 00:00:00
abstract:OBJECTIVE:Our aim was to examine maternal, obstetric, and infant characteristics of mother-to-child transmission of human immunodeficiency virus-1 in Nairobi, Kenya. STUDY DESIGN:Proviral human immunodeficiency virus-1 was detected by polymerase chain reaction in peripheral blood samples taken between 6 weeks and 3 mo...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(95)90597-9
更新日期:1995-02-01 00:00:00
abstract:OBJECTIVE:This study was designed to determine the intraobserver and interobserver variability in the visual assessment of fetal heart rate tracings and to evaluate the accuracy of the visual detection of accelerations and decelerations when compared with computerized fetal heart rate analysis. STUDY DESIGN:One hundre...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(12)90831-5
更新日期:1993-03-01 00:00:00
abstract::The biophysical profile has proved to be a valuable tool for the assessment of fetal well-being, independent of gestational age. Magnesium sulfate is commonly used as a tocolytic agent, yet relatively little is known about its effects on the biophysical activities of the fetus. To investigate the effects of magnesium ...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(89)90399-2
更新日期:1989-09-01 00:00:00
abstract::Mammography is presented for the primarily nonradiologic audience. A brief historical review calls attention to some of the milestones in mammography and how it has changed. Xerororadiography is discussed, as it is one of the newer developments and is rapidly gaining broad acceptance in the United States. Clinical app...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(76)90164-2
更新日期:1976-02-01 00:00:00
abstract::Although perimortem delivery has been recorded in the medical literature for millennia, the procedural intent has evolved to the current fetocentric approach, predicating timing of delivery following maternal cardiopulmonary arrest to optimize neonatal outcome. We suggest a call to action to reinforce the concept that...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章,评审
doi:10.1016/j.ajog.2015.07.019
更新日期:2015-11-01 00:00:00
abstract::Endocervical Chlamydia trachomatis infection was found in 13 of 162 volunteer female university students (8%). Infection was correlated with younger age (p less than 0.05), less than or equal to 4 years of intercourse (p less than 0.05), a history of gonorrhea (p less than 0.01), and exposure to a partner with urethri...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(85)80105-8
更新日期:1985-10-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to determine the rates of recurrent dysplasia with longer follow-up durations and to determine whether margin status and other variables were associated with recurrence. STUDY DESIGN:A retrospective chart review was performed for all women who underwent a loop electrosurgical excisi...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1067/mob.2001.109937
更新日期:2001-02-01 00:00:00
abstract:OBJECTIVE:The study was undertaken to identify the clinical characteristics associated with an abnormal clomiphene citrate challenge (CC) test. STUDY DESIGN:The medical records of 123 women seen in a referral-based infertility practice who had a CC test as part of their infertility workup were reviewed. Eighty-five pa...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1067/s0002-9378(03)00702-6
更新日期:2003-08-01 00:00:00
abstract::The effects of epidural analgesia on the duration of labor have been a controversal subject since its increased use in recent years. A total of 598 patients receiving this form of analgesia were studied as to progress in labor and eventual outcome. The mean cervical changes during epidural analgesia with a single drug...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(77)90790-6
更新日期:1977-10-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to test the null hypothesis that the volume of exercise at different times during pregnancy has no effect on fetoplacental growth. STUDY DESIGN:Seventy-five women who exercised regularly were evaluated before pregnancy and randomly assigned at 8 weeks' gestation to one of 3 exer...
journal_title:American journal of obstetrics and gynecology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1067/mob.2002.119109
更新日期:2002-01-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to determine the effect of docosahexaenoic acid supplementation on plasma phospholipid docosahexaenoic acid content and indices of depression and information processing for women who breast-feed. STUDY DESIGN:Mothers who planned to breast-feed their infants were assigned randoml...
journal_title:American journal of obstetrics and gynecology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1067/mob.2003.275
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understan...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2018.01.009
更新日期:2018-04-01 00:00:00
abstract::In a patient with polycystic ovarian disease, low-dose intravenous pulsatile gonadotropin-releasing hormone (5 mcg every hour) and no exogenous human chorionic gonadotropin induced multiple follicular development and elevated estrogen levels and resulted in a triplet pregnancy. Patients with polycystic ovarian disease...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(86)80017-5
更新日期:1986-10-01 00:00:00
abstract::Severe pregnancy-induced hypertension and markedly elevated levels of serum alkaline phosphatase developed in a 29-year-old-woman in whom one pregnancy resulted in intrauterine death. Acute fatty liver of pregnancy developed with good fetal outcome in the next pregnancy. This case suggests that pregnancy-induced hyper...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(90)90677-y
更新日期:1990-10-01 00:00:00
abstract:OBJECTIVE:Circulating adrenomedullin is increased in pregnancy, and placental and fetal membranes participate significantly in its secretion. Recent studies have suggested a potential role for this peptide in the regulation of fetoplacental circulation and placental hormonal secretion. Because adrenomedullin acts also ...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1067/mob.2001.117189
更新日期:2001-09-01 00:00:00
abstract:OBJECTIVE:We hypothesized that glycodelin stimulates vascular endothelial growth factor (VEGF) expression in response to oxidative stress. STUDY DESIGN:EM42 (human endometrial epithelial cell line) and primary endometrial epithelial cells were subjected to oxidative stress with minimally oxidized low density lipoprote...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2006.07.025
更新日期:2006-12-01 00:00:00
abstract:OBJECTIVE:We assessed intraobserver and interobserver variations in the performance of the amniotic fluid index. STUDY DESIGN:A total of 34 women in the third trimester with intact membranes were examined twice by each of three examiners. The amniotic fluid index was measured once by each of the three examiners in ord...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(93)90386-w
更新日期:1993-04-01 00:00:00
abstract::Serum corticosteroid-binding globulin (CBG) concentrations in blood respond to endogenous or exogenous estrogens in a dose-response manner and serve as a biologic assay for estrogens. Because endometrial carcinoma is associated with unopposed or excessive estrogen stimulation, the CBG binding capacity of sera of patie...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(81)90480-4
更新日期:1981-03-15 00:00:00
abstract:OBJECTIVE:Our purpose was to study the effects of the progestomimetic compound nomegestrol acetate on spontaneous and sulprostone-induced uterine contractility in pregnant cynomolgus monkeys. STUDY DESIGN:Intrauterine pressure was continuously monitored with use of an implanted intraamniotic catheter and a telemetric ...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(98)70643-x
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND:Use of more effective contraception may lead to less condom use and increased incidence of sexually transmitted infection. OBJECTIVE:The objective of this study was to compare changes in condom use and incidence of sexually transmitted infection acquisition among new initiators of long-acting reversible con...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2017.09.009
更新日期:2017-12-01 00:00:00
abstract:OBJECTIVE:Our purpose was to assess whether a program of expectant management of uncomplicated pregnancies in mothers with insulin-requiring gestational or pregestational class B reduces the incidence of cesarean birth. STUDY DESIGN:Two hundred women with uncomplicated, insulin-requiring diabetes at 38 weeks' gestatio...
journal_title:American journal of obstetrics and gynecology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0002-9378(93)90631-r
更新日期:1993-09-01 00:00:00
abstract::The serum vitamin B12 level falls progressively during pregnancy, when measured either by microbiologic assay or by a radioisotope dilution technique. The concentration of the vitamin assayed by radioisotope dilution was consistently higher than the value obtained by microbiologic assay. This discrepancy was greatest ...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(75)90609-2
更新日期:1975-05-01 00:00:00
abstract::The purpose of this investigation was to determine the diagnostic value of an average mean arterial blood pressure in the second trimester of greater than or equal to 90 mm Hg and a threshold increase in diastolic blood pressure of greater than or equal to 15 mm Hg or in systolic blood pressure of greater than or equa...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(89)90463-8
更新日期:1989-02-01 00:00:00
abstract:OBJECTIVE:Our purpose was to compare midtrimester amniocentesis-related fetal loss rates between obstetrician-gynecologists and perinatologists. STUDY DESIGN:This cohort study analyzes 1384 midtrimester amniocenteses from January 1, 1996, to December 31, 1999. Obstetrician-gynecologists who split their practices betwe...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1067/mob.2001.115049
更新日期:2001-06-01 00:00:00
abstract:OBJECTIVE:The objective of the study was a cost minimization analysis of the laparoscopic sacral colpopexy (LSC) and total vaginal mesh (TVM). STUDY DESIGN:Primary clinical costs were derived from our randomized control trial comparing LSC and TVM and were compared using prices from privately- and publicly-conducted p...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ajog.2011.12.012
更新日期:2012-05-01 00:00:00
abstract:OBJECTIVE:To define the incidence of hypoglycemia and identify risk factors in neonates from term, singleton, nondiabetic pregnancies. STUDY DESIGN:We conducted a matched case-control study of term, singleton infants weighing more than 2500 g in nondiabetic pregnancies. Cases with hypoglycemia (glucose < 50 mg/dL) wer...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2008.10.015
更新日期:2009-05-01 00:00:00
abstract::Postpartum women receiving gentamicin for endometritis were studied to determine if selective determination of gentamicin serum levels was cost-effective in terms of safety and efficacy. The women were randomized into two groups of 30 patients each. In the control group gentamicin serum levels were determined after th...
journal_title:American journal of obstetrics and gynecology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0002-9378(89)90431-6
更新日期:1989-02-01 00:00:00
abstract::An antiserum to 13,14-dihydro-15-keto-prostaglandin F2alpha (PGF2alphaM) was prepared and a radioimmunoassay evaluated in various reproductive states. PGF2alphaM plasma concentration was 63.6 +/- 10.3 pg/ml (mean +/- SEM) in cycling women. The concentration fluctuated throughout the menstrual cycle and pregnancy, but ...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(16)33031-9
更新日期:1979-06-01 00:00:00
abstract:OBJECTIVE:The aim of the study was to evaluate the following: (1) pregnancy outcome after blunt abdominal trauma and (2) factors that may predict preterm birth and adverse peripartum outcomes. STUDY DESIGN:All women who had noncatastrophic abdominal trauma and came to the labor and delivery suite July 1994-August 1997...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(98)70121-8
更新日期:1998-11-01 00:00:00