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1.
BMC Med Genet ; 19(1): 181, 2018 10 05.
Article in English | MEDLINE | ID: mdl-30290772

ABSTRACT

BACKGROUND: Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm birth, a complication that is more common in African Americans. Attempts to identify genetic loci associated with preterm birth using genome-wide association studies (GWAS) have only been successful with large numbers of cases and controls, and there has yet to be a convincing genetic association to explain racial/ethnic disparities. Indeed, the search for ancestry-specific variants associated with preterm birth has led to the conclusion that spontaneous preterm birth could be the consequence of multiple rare variants. The hypothesis that preterm birth is due to rare genetic variants that would go undetected in standard GWAS has been explored in the present study. The detection and validation of these rare variants present challenges because of the low allele frequency. However, some success in the identification of fetal loci/genes associated with preterm birth using whole genome sequencing and whole exome sequencing (WES) has recently been reported. While encouraging, this is currently an expensive technology, and methods to leverage the sequencing data to quickly identify and cost-effectively validate variants are needed. METHODS: We developed a WES data analysis strategy based on neonatal genomic DNA from PPROM cases and term controls that was unencumbered by preselection of candidate genes, and capable of identifying variants in African Americans worthy of focused evaluation to establish statistically significant associations. RESULTS: We describe this approach and the identification of damaging nonsense variants of African ancestry in the DEFB1 and MBL2 genes that encode anti-microbial proteins that presumably defend the fetal membranes from infectious agents. Our approach also enabled us to rule out a likely contribution of a predicted damaging nonsense variant in the METTL7B gene. CONCLUSIONS: Our findings support the notion that multiple rare population-specific variants in the fetal genome contribute to preterm birth associated with PPROM.


Subject(s)
Black People , Codon, Nonsense , Fetal Membranes, Premature Rupture/genetics , Genetic Predisposition to Disease , Mannose-Binding Lectin/genetics , Premature Birth/genetics , beta-Defensins/genetics , Adult , Alleles , Carrier Proteins/genetics , Case-Control Studies , Female , Fetal Membranes, Premature Rupture/ethnology , Fetal Membranes, Premature Rupture/pathology , Fetus , Gene Expression , Gene Frequency , Genome, Human , Humans , Infant, Newborn , Infant, Premature , Polymorphism, Single Nucleotide , Pregnancy , Premature Birth/ethnology , Premature Birth/pathology , Exome Sequencing
2.
Aust N Z J Obstet Gynaecol ; 56(3): 245-51, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26527192

ABSTRACT

BACKGROUND: Detailed analyses of long-term trends in Aboriginal maternal and newborn health characteristics are lacking. AIM: To examine trends in maternal and newborn health characteristics for all mothers who were recorded as Aboriginal in the Western Australian Midwives' Notification System from 1986 to 2009. MATERIALS AND METHODS: Births were categorised into four-year time intervals (1986-1989, 1990-1993, 1994-1997, 1998-2001, 2002-2005, 2006-2009). Trends in maternal demographic characteristics, pre-existing medical conditions, pregnancy complications and neonatal characteristics were examined. RESULTS: For 37 424 births recorded from 1986 to 2009, the proportion of births to mothers aged ≤19 years decreased (31-22%, P < 0.001) along with the prevalence of pre-eclampsia (6.8-4.0%, P < 0.001) and antepartum haemorrhage (4.8-3.2%, P < 0.001). There were increases in the prevalence of diabetes in pregnancy (3.8-6.6%, P < 0.001), induction of labour (17.8-21.4%, P < 0.001), elective caesarean (6.6-8.2%, P < 0.001) and emergency caesarean (9.5-14.9%, P < 0.001) deliveries. There were no changes in the overall prevalence of preterm births (15.4-15.9%, P = 0.32). However, increases were observed in the prevalence of medically indicated preterm births with and without prelabour rupture of membranes (1.0-1.7%; P < 0.001 and 3.3-4.3%; P = 0.005, respectively). There were no significant changes in the rates of smoking during pregnancy (51-52% from 1998 to 2009, P = 0.18), small-for-gestational age (16.9-17.2%, P = 0.07), suboptimal-birthweight (20.4-20.1%, P = 0.92), stillbirths (14.7 per 1000-12.1 per 1000, P = 0.22) and neonatal deaths (6.2 per 1000-5.5 per 1000, P = 0.68). CONCLUSION: Encouraging trends include reduced rates of teenage pregnancy, pre-eclampsia and antepartum haemorrhage. The persistent high rates of smoking during pregnancy, preterm births, stillbirths, neonatal deaths and increasing rates of diabetes in pregnancy are of concern.


Subject(s)
Fetal Membranes, Premature Rupture/ethnology , Labor, Induced/trends , Mothers/statistics & numerical data , Native Hawaiian or Other Pacific Islander/statistics & numerical data , Pregnancy in Adolescence/statistics & numerical data , Premature Birth/ethnology , Adolescent , Adult , Cesarean Section/trends , Demography/trends , Diabetes Mellitus/ethnology , Elective Surgical Procedures/trends , Female , Humans , Infant , Infant Mortality/trends , Infant, Low Birth Weight , Infant, Small for Gestational Age , Pre-Eclampsia/ethnology , Pregnancy , Prevalence , Smoking/trends , Stillbirth/ethnology , Uterine Hemorrhage/ethnology , Western Australia/epidemiology , Young Adult
3.
Ann Epidemiol ; 25(6): 392-397.e1, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25724829

ABSTRACT

PURPOSE: To examine whether maternal asthma contributes to racial/ethnic differences in obstetrical and neonatal complications. METHODS: Data on white (n = 110,603), black (n = 50,284), and Hispanic (n = 38,831) singleton deliveries came from the Consortium on Safe Labor. Multilevel logistic regression models, with an interaction term for asthma and race/ethnicity, estimated within-group adjusted odds ratios (aORs) for gestational diabetes, gestational hypertension, pre-eclampsia, placental abruption, premature rupture of membranes, preterm delivery, maternal hemorrhage, neonatal intensive care unit admissions, small for gestational age, apnea, respiratory distress syndrome, transient tachypnea of the newborn, anemia, and hyperbilirubinemia after adjustment for clinical and demographic confounders. Nonasthmatics of the same racial/ethnic group were the reference group. RESULTS: Compared with nonasthmatics, white asthmatics had increased odds of pre-eclampsia (aOR, 1.28; 95% confidence interval [CI], 1.15-1.43) and maternal hemorrhage (aOR, 1.14; 95% CI, 1.04-1.23). White and Hispanic infants were more likely to have neonatal intensive care unit admissions (aOR, 1.19; 95% CI, 1.11-1.28; aOR, 1.16; 95% CI, 1.02-1.32, respectively) and be small for gestational age (aOR, 1.11; 95% CI, 1.02-1.20; aOR, 1.26; 95% CI, 1.10-1.44, respectively), and Hispanic infants were more likely to have apnea (aOR, 1.32; 95% CI, 1.02-1.69). CONCLUSIONS: Maternal asthma did not affect most obstetrical and neonatal complication risks within racial/ethnic groups. Despite their increased risk for both asthma and many complications, our findings for black women were null. Asthma did not contribute to racial/ethnic disparities in complications.


Subject(s)
Asthma/ethnology , Health Status Disparities , Infant, Newborn, Diseases/ethnology , Pregnancy Complications/ethnology , Abruptio Placentae/ethnology , Adult , Apnea/ethnology , Asthma/complications , Black People , Delivery, Obstetric , Diabetes, Gestational/ethnology , Ethnicity , Female , Fetal Membranes, Premature Rupture/ethnology , Hispanic or Latino , Humans , Hyperbilirubinemia/ethnology , Infant, Newborn , Infant, Small for Gestational Age , Postpartum Hemorrhage/ethnology , Pre-Eclampsia/ethnology , Pregnancy , Premature Birth/ethnology , Respiratory Distress Syndrome, Newborn/ethnology , Retrospective Studies , Tachypnea/ethnology , United States , White People , Young Adult
4.
Am J Perinatol ; 31(6): 513-20, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24000110

ABSTRACT

OBJECTIVE: To compare obstetric and neonatal outcomes between human immunodeficiency virus (HIV) positive (HIV+) and HIV negative (HIV-) women and to determine if racial disparities exist among pregnancies complicated by HIV infection. STUDY DESIGN: This was a retrospective analysis of data from the Consortium of Safe Labor between 2002 and 2008. Comparisons of obstetric morbidity, neonatal morbidity, and indications for cesarean delivery were examined. Included were singletons with documented HIV status, race, and antepartum admission. Chi-square, Fisher exact tests, and logistic regression were used for statistical analysis. RESULTS: Included were 178,972 patients (178,210 HIV-, 762 HIV+, 464 HIV+ black, 298 HIV+ nonblack). HIV+ women were more likely to have a cesarean delivery, preterm premature rupture of membranes, another sexually transmitted infection, and delivery at an earlier gestational age. Obstetric outcomes were similar between HIV+ black and HIV+ nonblack women. Neonates of HIV+ mothers had lower birth weights and higher rates of neonatal intensive care admissions. HIV+ black women had lower birth weight neonates than HIV+ nonblack women. CONCLUSION: HIV+ women have higher rates of obstetric complications and deliver at an earlier gestational age than HIV- mothers. Lower birth weight was the only notable complication among HIV+ black women compared with HIV+ nonblack women.


Subject(s)
Black or African American/statistics & numerical data , Fetal Membranes, Premature Rupture/ethnology , HIV Seronegativity , HIV Seropositivity/ethnology , HIV-1 , Premature Birth/ethnology , Adult , Asian/statistics & numerical data , Birth Weight , Cesarean Section/statistics & numerical data , Female , Fetal Membranes, Premature Rupture/virology , Gestational Age , HIV Seropositivity/virology , Health Status Disparities , Hispanic or Latino/statistics & numerical data , Humans , Intensive Care, Neonatal/statistics & numerical data , Pregnancy , Premature Birth/virology , Retrospective Studies , United States/epidemiology , White People/statistics & numerical data , Young Adult
5.
Int J Gynecol Cancer ; 23(4): 710-5, 2013 May.
Article in English | MEDLINE | ID: mdl-23446377

ABSTRACT

OBJECTIVE: The objective of this study was to assess the adverse pregnancy outcomes in women who had treatment for cervical intraepithelial neoplasia. METHODS: This was a retrospective cohort using data linkage. Pathology databases from Whipps Cross University Hospital were used to identify women with a histological sample taken at colposcopy between 1995 and 2009. Births for these women were identified through the hospitals' obstetric database. A total of 876 births (from 721 women) were identified. Logistic regression was used to assess the relationship between adverse pregnancy outcomes and treatment for cervical intraepithelial neoplasia before delivery. Results were adjusted by ethnicity, deprivation, and parity. RESULTS: After taking into account parity, socioeconomic status, and ethnicity, receiving any type of excisional treatment (single or multiple) before birth increased the risk of preterm labor compared with having a punch biopsy only (adjusted relative risk, 1.61; 95% confidence interval, 1.11-2.32). Preterm deliveries that occurred after a spontaneous onset of labor were found to be more likely after treatment for cervical disease (adjusted relative risk, 1.68; 95% confidence interval, 1.11-2.52). CONCLUSIONS: Women receiving any type of excisional treatment before delivery are at increased risk of preterm delivery when compared with women attending colposcopy but not treated. Although we took into account the effects of parity, socioeconomic status, and ethnicity, residual confounding factors may be unidentified.


Subject(s)
Colposcopy/adverse effects , Premature Birth/etiology , Uterine Cervical Dysplasia/surgery , Uterine Cervical Neoplasms/surgery , Adult , Cesarean Section/economics , Colposcopy/economics , Female , Fetal Membranes, Premature Rupture/economics , Fetal Membranes, Premature Rupture/ethnology , Fetal Membranes, Premature Rupture/etiology , Humans , Infant, Low Birth Weight , Infant, Newborn , Pregnancy , Pregnancy Outcome/economics , Pregnancy Outcome/ethnology , Premature Birth/economics , Premature Birth/ethnology , Retrospective Studies , State Medicine/economics , United Kingdom/ethnology , Uterine Cervical Neoplasms/economics , Uterine Cervical Neoplasms/ethnology , Uterine Cervical Dysplasia/economics , Uterine Cervical Dysplasia/ethnology
6.
Am J Obstet Gynecol ; 202(6): 570.e1-6, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20132922

ABSTRACT

OBJECTIVE: The purpose of this study was to examine whether the recurrence risk of preterm premature rupture of membranes (PPROM) is modified by the interpregnancy interval (IPI). STUDY DESIGN: We used the Missouri 1989-1997 longitudinally linked data to examine the recurrence risk of PPROM in women with first 2 (n = 150,929) and first 3 (n = 30,011) successive pregnancies. Race-specific recurrence risks were examined. Adjusted odds ratios (ORs) were used to estimate risks. RESULTS: Risks of PPROM in the second pregnancy among women with and without previous PPROM were 5.7% and 2.3%, respectively, among white women (OR, 8.7; 95% confidence interval, 6.7-11.4) and 10.3% and 4.3%, respectively, among African American women (OR, 7.2; 95% confidence interval, 5.1-10.1). Short IPI was associated with increased risk for PPROM recurrence, with substantially higher risk for African American women than white women. However, long IPI was associated with increased recurrence among African American women. CONCLUSION: Women with previous PPROM are at increased risk for recurrence, and a short IPI is associated with increased risk.


Subject(s)
Fetal Membranes, Premature Rupture/physiopathology , Risk Assessment , Adult , Female , Fetal Membranes, Premature Rupture/ethnology , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Longitudinal Studies , Odds Ratio , Pregnancy , Recurrence , Risk , Risk Factors
7.
Yonsei Med J ; 50(1): 132-6, 2009 Feb 28.
Article in English | MEDLINE | ID: mdl-19259359

ABSTRACT

PURPOSE: To investigate whether allelic polymorphism of haptoglobin (Hp) is associated with premature rupture of membrane (PROM), the Hp phenotypes of pregnant women with PROM were analyzed. PATIENTS AND METHODS: The Hp phenotypes of 221 pregnant Korean women (187 control and 34 PROM patients) were determined by benzidine/hydrogen peroxide staining, following native polyacrylamide gel electrophoresis of hemoglobin-mixed sera. The Hp allele frequencies were calculated from the data of Hp phenotypes, and overall association with PROM was evaluated using Pearson Chi-Square test. RESULTS: The polymorphic distribution of the patients cohort who underwent a normal delivery (control group) was similar to that of healthy Koreans. In contrast, however, patients with PROM showed significantly higher occurrence of the Hp 1-1 phenotype than control group (23.5% vs 8.0%). Hp 2-2 phenotype was lower in PROM cohort (38.2%) than in the control group (48.7%). The Hp(1) allele frequency in PROM group was significantly higher than that in the control group (0.426 vs 0.297, p = 0.034) with odds ratio of 1.762 (95% CI: 1.038 - 2.991). CONCLUSION: These findings suggest that pregnant Korean women who possess Hp(1) allele (expressed as Hp 1-1 phenotype) have higher incidence of PROM than women with Hp(2) allele (expressed as Hp 2-2 phenotype). This is the first study that evaluated the significance of Hp polymorphism with respect to the development of PROM.


Subject(s)
Asian People/statistics & numerical data , Fetal Membranes, Premature Rupture/ethnology , Fetal Membranes, Premature Rupture/genetics , Haptoglobins/genetics , Polymorphism, Genetic , Adult , Female , Gene Frequency , Genetic Predisposition to Disease/ethnology , Humans , Incidence , Infant, Newborn , Korea/epidemiology , Phenotype , Pregnancy
8.
Yonsei Medical Journal ; : 132-136, 2009.
Article in English | WPRIM (Western Pacific) | ID: wpr-52282

ABSTRACT

PURPOSE: To investigate whether allelic polymorphism of haptoglobin (Hp) is associated with premature rupture of membrane (PROM), the Hp phenotypes of pregnant women with PROM were analyzed. PATIENTS AND METHODS: The Hp phenotypes of 221 pregnant Korean women (187 control and 34 PROM patients) were determined by benzidine/hydrogen peroxide staining, following native polyacrylamide gel electrophoresis of hemoglobin-mixed sera. The Hp allele frequencies were calculated from the data of Hp phenotypes, and overall association with PROM was evaluated using Pearson Chi-Square test. RESULTS: The polymorphic distribution of the patients cohort who underwent a normal delivery (control group) was similar to that of healthy Koreans. In contrast, however, patients with PROM showed significantly higher occurrence of the Hp 1-1 phenotype than control group (23.5% vs 8.0%). Hp 2-2 phenotype was lower in PROM cohort (38.2%) than in the control group (48.7%). The Hp1 allele frequency in PROM group was significantly higher than that in the control group (0.426 vs 0.297, p = 0.034) with odds ratio of 1.762 (95% CI: 1.038 - 2.991). CONCLUSION: These findings suggest that pregnant Korean women who possess Hp1 allele (expressed as Hp 1-1 phenotype) have higher incidence of PROM than women with Hp2 allele (expressed as Hp 2-2 phenotype). This is the first study that evaluated the significance of Hp polymorphism with respect to the development of PROM.


Subject(s)
Adult , Female , Humans , Infant, Newborn , Pregnancy , Asian People/statistics & numerical data , Fetal Membranes, Premature Rupture/ethnology , Gene Frequency , Genetic Predisposition to Disease/ethnology , Haptoglobins/genetics , Incidence , Korea/epidemiology , Phenotype , Polymorphism, Genetic
9.
Am J Obstet Gynecol ; 199(4): 373.e1-7, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18667175

ABSTRACT

OBJECTIVE: The purpose of this study was to test the hypothesis that race is associated with the risk of preterm birth due to preterm premature rupture of membranes (PPROM) and its recurrence. STUDY DESIGN: We conducted a population-based cohort study using the Missouri Department of Health's maternally linked birth certificate database (1989-1997) to assess racial effects on the occurrence and recurrence of PPROM, while adjusting for socioeconomic and maternal medical risk factors (n = 644,462). RESULTS: Black mothers were more likely to have PPROM compared to white mothers (aOR, 2.3; 95% CI, 2.0-2.5). The magnitude of risk of PPROM for black mothers compared to white mothers was greatest at < 28 weeks of gestation (aOR 2.8, 95% CI, 2.5-3.2). Black mothers were at significantly higher risk of recurrent PPROM compared to white mothers (aOR 6.4, 95% CI, 3.7-11.0). CONCLUSION: There is an overrepresentation in the occurrence and recurrence of PPROM in black mothers that persists after adjusting for known risk factors.


Subject(s)
Black or African American/statistics & numerical data , Fetal Membranes, Premature Rupture/ethnology , Adult , Female , Humans , Missouri/epidemiology , Multivariate Analysis , Pregnancy , Recurrence , Risk Factors , Socioeconomic Factors
10.
Hum Mutat ; 29(2): 332, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18205191

ABSTRACT

We identified a novel 12-bp deletion NT_033927.7: g.5495364_5495375del in the 5'-flanking region of the SERPINH1 gene that increases promoter activity. The 12-bp deletion is in linkage disequilibrium with the minor "T" allele of the -656 C/T SNP (NT_033927.7(SERPINH1):g.5495402C>T) that reduces promoter activity in amnion fibroblast cells and is associated with a significantly increased risk of preterm birth as a result of premature rupture of membranes. In a case-control study, fetal carriage of the 12-bp deletion was found to protect against PPROM, apparently overcoming the influence of the SERPINH1 -656 "T" allele. These studies define a new haplotype in the SERPINH1 gene that modifies risk of an adverse obstetrical outcome.


Subject(s)
5' Flanking Region/genetics , Base Pairing , Black or African American/genetics , Fetal Membranes, Premature Rupture/prevention & control , HSP47 Heat-Shock Proteins/genetics , Promoter Regions, Genetic/genetics , Sequence Deletion , Black or African American/ethnology , Case-Control Studies , Cells, Cultured , Female , Fetal Membranes, Premature Rupture/ethnology , Humans , Pregnancy
12.
Proc Natl Acad Sci U S A ; 103(36): 13463-7, 2006 Sep 05.
Article in English | MEDLINE | ID: mdl-16938879

ABSTRACT

Prematurity is more prevalent in African Americans than in European Americans. We investigated the contribution of a functional SNP in the promoter of the SERPINH1 gene, enriched among those of African ancestry, to preterm premature rupture of membranes (PPROM), the leading identifiable cause of preterm birth. SERPINH1 encodes heat-shock protein 47, a chaperone essential for collagen synthesis. The SERPINH1 -656 minor T allele had a greater frequency in African populations and African Americans than in European Americans (7.4% [corrected] vs. 4.1%). The -656 T allele displayed significantly reduced promoter activity compared to the major -656 C allele in amnion fibroblasts, which lay down the fibrillar collagen that gives tensile strength to the amnion. An initial case-control study demonstrated that the -656 T allele is significantly more frequent in African-American neonates (P < 0.0009) born from pregnancies complicated by PPROM compared with controls (odds ratio of 3.22, 95% confidence interval 1.50, 7.22). There was no significant difference in ancestry among cases and controls using a dihybrid model based on 29 ancestry-informative markers. Adjusting the results of the case-control study for admixture still yielded a statistically significant association between the -656 T allele and PPROM (P < 0.002). A follow-up case-control study gave similar results. The combined case-control findings showed a highly significant (P < 0.0000045) association between the -656 T allele and PPROM. The SERPINH1 -656 T allele is the first example of an ancestry-informative marker associated with preterm birth in African Americans.


Subject(s)
Fetal Membranes, Premature Rupture/genetics , HSP47 Heat-Shock Proteins/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Black or African American , Alleles , Birth Weight , Black People/genetics , Case-Control Studies , Female , Fetal Membranes, Premature Rupture/ethnology , Gene Expression , Gene Frequency , Gestational Age , HSP47 Heat-Shock Proteins/metabolism , Humans , Infant, Newborn , Infant, Premature , Pregnancy , Risk Factors
13.
Hum Mol Genet ; 13(21): 2659-69, 2004 Nov 01.
Article in English | MEDLINE | ID: mdl-15367487

ABSTRACT

Matrix metalloproteinase 8 (MMP8), an enzyme that degrades fibrillar collagens imparting strength to the fetal membranes, is expressed by leukocytes and chorionic cytotrophoblast cells. We identified three single nucleotide polymorphisms (SNPs) at -799C/T, -381A/G and +17C/G from the major transcription start site in the MMP8 gene, and determined the functional significance of these SNPs by analyzing their impact upon MMP8 promoter activity and their association with preterm premature rupture of membranes (PPROM). The minor alleles +17 (G) and -381 (G) were in complete linkage disequilibrium. A promoter fragment containing the three minor alleles had 3-fold greater activity in chorion-like trophoblast cells (BeWo, JEG-3 and HTR-8/SVneo) compared with the major allele promoter construct. Electrophoretic mobility shift assays revealed differences in BeWo nuclear protein binding to oligonucleotides representing the -381 and -799 SNPs, suggesting that the minor alleles have reduced transcription factor binding. A case-control study of African-American neonates using allele-specific primers revealed a statistically significant association between the three minor allele haplotype, which displays the highest MMP8 promoter activity in trophoblast cells, with PPROM with an odds ratio (OR) of 4.63 (P < 0.0001), whereas the major allele promoter appeared to be protective (OR = 0.52, P < 0.0002). None of the minor alleles were individually associated with PPROM. These findings demonstrate the functional significance of SNP haplotypes in the MMP8 gene and associations with obstetrical outcomes.


Subject(s)
Fetal Membranes, Premature Rupture/genetics , Haplotypes , Matrix Metalloproteinase 8/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Alleles , Alternative Splicing , Base Sequence , Black People/genetics , Case-Control Studies , Cell Line , Chromosome Mapping , Electrophoretic Mobility Shift Assay , Female , Fetal Membranes, Premature Rupture/ethnology , Gene Frequency , Humans , Infant, Newborn , Infant, Premature , Luciferases/metabolism , Matrix Metalloproteinase 8/chemistry , Molecular Sequence Data , Odds Ratio , Pregnancy , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Nucleic Acid , U937 Cells
14.
Am J Obstet Gynecol ; 187(1): 157-63, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12114904

ABSTRACT

OBJECTIVE: We examined the association between preterm delivery and polymorphisms at position +3953 of the interleukin-1 beta gene (IL1B+3953) and in intron 2 of the interleukin-1 receptor antagonist gene (IL1RN). STUDY DESIGN: This was a case-control study that involved 52 pregnancies that resulted in spontaneous preterm delivery before 34 weeks of gestation and 197 pregnancies that resulted in birth at term. Polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Homozygous carriage of IL1B+3953 allele 1 by fetuses of African descent was associated with a risk of preterm delivery (P =.033). Fetuses of Hispanic descent that carried IL1RN allele 2 were found to be at an increased risk for preterm premature rupture of membranes and subsequent preterm delivery(P =.021; odds ratio, 6.5; 95% CI, 1.25-37.7). CONCLUSION: There are associations of spontaneous preterm delivery with the fetal carriage of IL1B+3953*1 and IL1RN*2 alleles in African and Hispanic populations, respectively.


Subject(s)
Fetal Membranes, Premature Rupture/genetics , Interleukin-1/genetics , Obstetric Labor, Premature/genetics , Polymorphism, Genetic , Receptors, Interleukin-1/antagonists & inhibitors , Adult , Black People/genetics , Case-Control Studies , Chromosomes, Human, Pair 2 , Female , Fetal Membranes, Premature Rupture/ethnology , Heterozygote , Hispanic or Latino/genetics , Homozygote , Humans , Obstetric Labor, Premature/ethnology , Polymerase Chain Reaction , Pregnancy
15.
Mol Hum Reprod ; 8(5): 494-501, 2002 May.
Article in English | MEDLINE | ID: mdl-11994547

ABSTRACT

Fetal membrane rupture is associated with increased expression of matrix metalloproteinase-9 (MMP-9) and matrix degradation. We have determined the functional significance of a variable number tandem repeat and a single nucleotide polymorphism (SNP) in the MMP-9 gene on promoter activity and their association with preterm premature rupture of membranes (PPROM). The 14 CA-repeat allele was a stronger promoter than the 20 CA-repeat allele in amnion epithelial cells and WISH amnion-derived cells, but in THP-1 monocyte/macrophage cells the 14 and 20 CA-repeat alleles had similar activities. An SNP at -1562 did not significantly affect promoter activity. A case-control study of African American neonates revealed that the 14 CA-repeat allele was more common in newborns delivered of mothers who had PPROM than in those delivered at term. There was no association between the -1562 SNP and PPROM. We conclude that there are cell host-dependent differences in MMP-9 promoter activity related to CA-repeat number and that fetal carriage of the 14 CA-repeat allele is associated with PPROM in African Americans.


Subject(s)
Fetal Membranes, Premature Rupture/genetics , Matrix Metalloproteinase 9/genetics , Polymorphism, Genetic , Promoter Regions, Genetic , Black or African American , Amnion/cytology , Amnion/physiology , Black People/genetics , Case-Control Studies , Cells, Cultured , Epithelial Cells/cytology , Female , Fetal Membranes, Premature Rupture/ethnology , Gene Frequency , Genetic Predisposition to Disease , Humans , Infant, Newborn , Infant, Premature , Polymorphism, Single Nucleotide , Pregnancy , Tandem Repeat Sequences
16.
Obstet Gynecol ; 88(3): 356-63, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8752239

ABSTRACT

OBJECTIVE: To explore associations between race, preterm delivery, etiologic classification of preterm delivery, and perinatal mortality. METHODS: The study population consisted of 13,010 black and 19,007 white mother-infant pairs delivered at Chicago-area hospitals in 1988-1989 categorized as term or preterm births. Preterm births were further divided by severity and etiology. Black-white differences in perinatal mortality within groups were calculated and adjusted for birth weight and other potential confounding variables. RESULTS: Black women were nearly twice as likely as whites to experience preterm (before 37 weeks' gestation) and very preterm (before 32 weeks' gestation) delivery associated with premature rupture of membranes (PROM) or classified as idiopathic. Although black infants were also found to have twice the perinatal mortality risk of white infants (relative risk [RR] 2.1, 95% confidence interval [CI] 1.7-2.5), the overall preterm perinatal mortality rates did not differ between black and white women (RR 1.0, 95% CI 0.8-1.2). However, among preterm births, perinatal mortality was not uniform within categories of medical etiology. The mortality risk was the same for black and white infants born preterm following polyhydramnios or placental complications (RR 1.1, 95% CI 0.6-1.9), the same for black and white infants born preterm after labor induction (RR 1.1, 95% CI 0.6-1.9), and higher for black infants classified as idiopathic preterm deliveries (RR 1.6, 95% CI 1.1-2.3). In contrast, mortality rates tended to be lower for black infants born preterm following PROM-amnionitis (RR 0.8, 95% CI 0.5-1.2). The idiopathic disparity was explained by a differential birth weight distribution (adjusted RR 1.1, 95% CI 0.7-1.9); however, the apparent survival benefit among black infants born preterm following PROM increased even further after adjustment for birth weight (adjusted RR 0.4, 95% CI 0.2-0.7). CONCLUSION: Black infants born preterm after PROM appear to have a survival advantage compared with their white counterparts, an effect not observed within other etiologic categories of preterm delivery.


Subject(s)
Black or African American , Infant Mortality , Obstetric Labor, Premature/ethnology , Adult , Chicago/epidemiology , Chorioamnionitis/ethnology , Cohort Studies , Female , Fetal Membranes, Premature Rupture/ethnology , Gestational Age , Humans , Infant, Newborn , Insurance, Health/statistics & numerical data , Logistic Models , Medicaid/statistics & numerical data , Obstetric Labor, Premature/etiology , Pregnancy , Pregnancy Complications/ethnology , Registries , Risk Factors , United States , White People
17.
Am J Obstet Gynecol ; 173(4): 1310-5, 1995 Oct.
Article in English | MEDLINE | ID: mdl-7485344

ABSTRACT

OBJECTIVE: Our purpose was to determine risk factors predictive of preterm premature rupture of the membranes in women treated for preterm labor with intact membranes. STUDY DESIGN: Women with intact membranes participating in a National Institute of Child Health and Human Development multicenter randomized trial of adjunctive antibiotic therapy for preterm labor (24 to 34 weeks) were studied (n = 275). After randomization, 22 women continued to have contractions and were delivered of their infants. The remaining 253 women whose contractions had ceased composed our study population. Preterm premature rupture of the membranes was diagnosed if ruptured membranes occurred > or = 1 hour before the onset of recurrent preterm labor. As part of the study protocol, most women underwent amniocentesis on admission. RESULTS: Preterm premature rupture of the membranes developed in 44% women (17.4%). Women who had preterm premature rupture of the membranes were more likely to be black (p = 0.004), to be multiparous (p = 0.014), to have a history of abortion(s) (p = 0.001), to have had a preterm birth(s) (p = 0.036), to have early onset preterm labor (p = 0.04), to have more advanced cervical dilatation (p = 0.0001), to have one or more amniotic fluid markers suggestive of infection (p = 0.01, odds ratio 4.2), and to have positive amniotic fluid cultures (p = 0.0007, odds ratio 27). Assignment to antibiotic therapy did not prevent preterm premature rupture of the membranes in the 253 women randomized or in the 16 women with a positive amniotic fluid marker(s) of infection. CONCLUSION: Black race, multiparity, a history of abortion or preterm birth, advanced dilatation, and a positive amniotic fluid marker(s) are associated with preterm premature rupture of the membranes in women with preterm labor. Antibiotic treatment did not prevent preterm premature rupture of the membranes.


Subject(s)
Fetal Membranes, Premature Rupture/epidemiology , Obstetric Labor, Premature/complications , Abortion, Spontaneous/epidemiology , Amniotic Fluid/microbiology , Anti-Bacterial Agents/therapeutic use , Black People , Chi-Square Distribution , Chorioamnionitis/complications , Chorioamnionitis/drug therapy , Chorioamnionitis/microbiology , Female , Fetal Membranes, Premature Rupture/ethnology , Fetal Membranes, Premature Rupture/etiology , Humans , Labor Onset , Logistic Models , Multivariate Analysis , Obstetric Labor, Premature/drug therapy , Odds Ratio , Parity , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/microbiology , Risk Factors , United States
18.
Paediatr Perinat Epidemiol ; 9(3): 281-95, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7479277

ABSTRACT

In order to assess racial differences in rates of idiopathic preterm labour, preterm premature rupture of membranes, and medically indicated preterm delivery, the authors analysed data on 388 preterm (< 37 completed weeks of gestation) births (7.9% of all births) occurring between 1 September 1988 and 31 August 1989, in three central North Carolina counties. The crude relative risk (RR) of preterm birth among black women compared with white women was 2.6 [95% confidence interval (CI) 2.1, 3.1]. With adjustment for age, gravidity, marital status, education, and county of residence, the estimated relative risk for black women compared with white women was 2.1 (95% CI 1.1, 4.1) for medically indicated preterm delivery, 1.6 (95% CI 1.1, 2.3) for preterm birth as a result of preterm labour, and 1.9 (95% CI 1.2, 3.1) for preterm premature rupture of membranes. Compared with white women, black women were at the highest risk of a preterm birth before 34 weeks of gestation (RR = 2.9; 95% CI 1.8, 4.7). The risk of medically indicated preterm delivery at 36 weeks was considerably higher for black women than for white women (RR = 3.4; 95% CI 1.1, 10.2). For a better understanding and ultimately a reduction of the risk for preterm delivery among black women, investigation of specific aetiological pathways and gestational age groups may be required.


Subject(s)
Black or African American/statistics & numerical data , Fetal Membranes, Premature Rupture/ethnology , Labor, Induced , Obstetric Labor, Premature/ethnology , White People/statistics & numerical data , Adolescent , Adult , Bias , Female , Fetal Membranes, Premature Rupture/epidemiology , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Likelihood Functions , Logistic Models , North Carolina/epidemiology , Obstetric Labor, Premature/epidemiology , Obstetric Labor, Premature/etiology , Odds Ratio , Pregnancy , Risk Factors
19.
J Nutr ; 124(6 Suppl): 987S-993S, 1994 06.
Article in English | MEDLINE | ID: mdl-8201450

ABSTRACT

Using a prospective comparative design, African American gravidae with and without genital tract infection were assessed with respect to dietary intakes, serum nutrient values, hematologic values, and pregnancy outcomes. Intakes of ascorbic acid, vitamin A, protein, and iron were the dietary variables while levels of ascorbic acid, protein, albumin, globulin, and ferritin were the variables measured in serum. The hematologic variables included hemoglobin, hematocrit, and red and white blood cell counts. Pregnancy outcome was defined on the basis of premature rupture of the membranes (PROM), and infant birth weight, birth length, gestational age, and head circumference. The sample consisted of 335 nulliparous women who were between 16-35 years of age, 96 of whom had genital tract infection based on laboratory reports. Findings indicated no significant differences between the mean dietary intakes as well as serum values of the infected and non-infected women, and no difference in the incidence of PROM. However, non-infected women had a better mean hematologic profile than the infected gravidae during pregnancy. Also, for the non-infected group, there were significant relationships between head circumference and protein consumption (P = .015) and serum ferritin (P = .05). For the infected women, the relationship between the hemoglobin and hematocrit measurements obtained at the first prenatal visit and infant birth weight, birth length and head circumference were statistically significant.


Subject(s)
Black or African American , Diet , Fetal Membranes, Premature Rupture/ethnology , Pregnancy Complications, Infectious/ethnology , Pregnancy Outcome/ethnology , Vaginitis/ethnology , Adolescent , Adult , Ascorbic Acid/administration & dosage , Ascorbic Acid/blood , Birth Weight , Candidiasis, Vulvovaginal/complications , Candidiasis, Vulvovaginal/ethnology , Dietary Proteins/administration & dosage , Dietary Proteins/blood , District of Columbia/epidemiology , Female , Fetal Membranes, Premature Rupture/complications , Gestational Age , Hematocrit , Humans , Infant, Newborn , Iron/administration & dosage , Iron/blood , Labor, Obstetric/blood , Pregnancy , Prospective Studies , Vaginitis/complications , Vaginosis, Bacterial/complications , Vaginosis, Bacterial/ethnology , Vitamin A/administration & dosage , Vitamin A/blood
20.
Am J Epidemiol ; 129(3): 604-15, 1989 Mar.
Article in English | MEDLINE | ID: mdl-2916554

ABSTRACT

From 1980 to 1982, a sample of 968 pregnant Navajo women in New Mexico was enrolled in a prospective study of biologic and sociocultural factors in puerperal infectious morbidity. Past studies have independently implicated both genital infection and psychosocial stressors in perinatal complications, but, to the authors' knowledge, no previous work has concurrently investigated the interactive effects of genital pathogens and psychosocial processes. Endocervical cultures for Mycoplasma hominis and Chlamydia trachomatis were obtained during prenatal visits, and structured interviews were conducted assessing social support and the degree of cultural traditionality, in this context a proxy measure of acculturative stress. The incidences of postpartum fever, endometritis, and premature rupture of membranes were significantly associated with the concurrence of two factors: the presence of genital tract M. hominis and a highly traditional cultural orientation. When demographic and conventional obstetric risk factors were controlled for, women with both M. hominis and high traditionality experienced infectious complications at a rate twice that of women with either factor alone. Among the plausible explanations for this result is the possibility that acculturative stress undermines physiologic resistance to infectious genital tract disease.


Subject(s)
Cultural Deprivation , Indians, North American , Puerperal Infection/ethnology , Adolescent , Adult , Chlamydia Infections/ethnology , Chlamydia trachomatis , Endometritis/ethnology , Epidemiologic Methods , Female , Fetal Membranes, Premature Rupture/ethnology , Humans , Mycoplasma Infections/ethnology , New Mexico , Parity , Pregnancy , Puerperal Infection/etiology , Risk Factors , Socioeconomic Factors
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