beta2-Adrenergic receptor genotype and preterm delivery

OBJECTIVE: Our purpose was to determine whether the functional genetic polymorphisms of the beta(2)-adrenergic receptor (beta(2)AR) that result in changes in amino acid residues 16 and 27 are associated with preterm delivery. STUDY DESIGN: A case-control study comparing the distribution of beta(2)AR genotype between 251 Hispanic women delivered at term and 28 Hispanic women delivered preterm. Preterm delivery was defined as spontaneous onset of labor resulting in delivery before 37 weeks of gestation, in a singleton pregnancy, with no apparent etiology for preterm labor and delivery. Genomic DNA was isolated from peripheral blood, and beta( 2)AR alleles were identified by established techniques. RESULTS: Only one woman (4%) with preterm labor was homozygous for Arg16 versus 79 (31%) in the control group (P =.01, odds ratio 0.08). There was no association of preterm labor with genotype at position 27. CONCLUSION: Our data demonstrate that homozygosity for Arg16, which in vitro is associated with decreased down-regulation of the beta(2)AR, protects from preterm delivery.     

Interleukin-4 and -10 gene polymorphisms and spontaneous preterm birth in multifetal gestations

OBJECTIVE: The purpose of this study was to determine the relationship between maternal and fetal carriage of different alleles of interleukin-4 and -10 genes and pregnancy outcome in multifetal gestations. STUDY DESIGN: Buccal swabs from mother-infant pairs of 73 multifetal gestations were assayed for polymorphisms at position -590 of the interleukin-4 gene and position -1082 of the interleukin-10 gene. Pregnancy outcome data were obtained subsequently. RESULTS: Spontaneous preterm birth occurred in 29 of the pregnancies (39.7%). A higher frequency of the interleukin-4 T allele was found among mothers with spontaneous preterm birth compared with mothers without spontaneous preterm birth (36.2% vs 18.2%; P=.02; odds ratio, 2.6; 95% CI, 1.1-5.9). Moreover, 20.7% of mothers who had spontaneous preterm birth were homozygous for the interleukin-4 T allele, as opposed to only 2.3% of mothers who did not have a spontaneous preterm birth (P=.01; odds ratio, 11.2; 95% CI, 1.2-69.5). Similarly, in 55.2% of the pregnancies that were complicated by spontaneous preterm birth, 2 fetuses carried the interleukin-4 T allele, compared with only 29.5% of the pregnancies that were not complicated by spontaneous preterm birth (p<.05; odds ratio, 2.9; 95% CI, 1.0-8.8). There was no relationship between mother and infant IL-10 genotype and spontaneous preterm birth. CONCLUSION: Maternal and fetal carriage of the interleukin-4 T allele is associated with an increased risk of spontaneous preterm birth in multifetal gestations.     

Fetal polymorphisms in anti-inflammatory cytokine and beta-adrenergic receptor genes associated with placental pathological lesions.

Prematurity is the leading cause of infant morbidity and mortality. Altered intra-amniotic levels of anti-inflammatory cytokines, interleukin (IL) 1ra and IL-4, and beta2-adrenergic receptor (beta2AR) production have been associated with preterm labor and delivery. The aim of this study was to evaluate potential associations of polymorphisms in these genes with specific placental pathological findings. Maternal and fetal DNA were analyzed for a length polymorphism in the IL-1ra gene and for single nucleotide polymorphisms in the IL-4 and beta2AR genes. Placentas were evaluated for pathological abnormalities in the following major categories: meconium, malperfusion, acute deciduitis, chorioamnionitis, umbilical cord problems, villitis, and fetal vascular thrombosis. In fetal DNA, homozygosity for the IL-1ra 2 allele (P = 0.029) and carriage of the IL-4 T allele (P < 0.01) were associated with acute deciduitis. In addition, carriage of the beta2AR A allele (P = 0.036) was associated with umbilical cord problems. There were no associations between placental lesions and any maternal gene polymorphisms. Although susceptibility to premature delivery is multifactorial, the present study provides pathological evidence for a connection between specific alleles and placental abnormalities. Carriage of these alleles may render the fetus more susceptible to the adverse consequences of infection and inflammation.     

Association of the Gln27Glu polymorphism of the beta-2-adrenergic receptor with preterm labor.

OBJECTIVES: To investigate a potential association between the beta-2-adrenergic receptor (B2AR) polymorphisms occurring at amino acid positions 16 (Arg16Gly) and 27 (Gln27Glu) and preterm labor. METHODS: Eighty patients with preterm labor and 76 control subjects were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A significant association was found between Gln27Glu substitution and preterm labor (P=0.001). The frequency of Gly16 and Glu27 alleles were found to be higher in patients than in control women (0.54 vs. 0.48 and 0.42 vs. 0.26, respectively), and the odds ratio for the occurrence of preterm labor was 2.14 (95% CI, 1.32-3.46; P=0.002) for the Glu 27 allele. An early delivery was noted in 52.5% of patients. CONCLUSION: The Gln27Glu polymorphism of the B2AR gene may have a role in molecular pathogenesis of preterm labor. Glu27 allele in patients with preterm labor might be a risk factor for deliveries before 37 weeks of gestation.     

Polymorphism in the interleukin-1 gene complex and spontaneous preterm delivery

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.     

A polymorphism in the promoter region of TNF and bacterial vaginosis: preliminary evidence of gene-environment interaction in the etiology of spontaneous preterm birth

OBJECTIVE: The rarer of 2 alleles of a polymorphism in the promoter of the tumor necrosis factor alpha gene (TNF) has been associated with spontaneous preterm birth following preterm premature rupture of the fetal membranes in some populations. The aim of this study was to assess if the presence of symptomatic bacterial vaginosis amplifies the risk of spontaneous preterm birth in those with a "susceptible" TNF genotype. STUDY DESIGN: A case-control study was performed at our institution. Cases (n=125) were defined as women who delivered before 37 weeks as a result of ruptured membranes or preterm labor, while control subjects (n=250) were defined as women who delivered after 37 weeks. DNA was collected from maternal blood and analyzed for the TNF genotype. Information on symptomatic bacterial vaginosis and other risk factors for preterm birth was obtained by review of the antenatal record. Multiple logistic regression was also used to test the interaction between bacterial vaginosis, the TNF genotype, and preterm birth. RESULTS: Maternal carriers of the rarer allele (TNF-2) were at a significantly increased risk of spontaneous preterm birth [odds ratio (OR) 2.7, 95% CI 1.7-4.5]. The association between TNF-2 and preterm birth was modified by the presence of bacterial vaginosis, such that those with a "susceptible" genotype and bacterial vaginosis had increased odds of preterm birth compared with those who did not (OR 6.1, 95% CI 1.9-21.0). CONCLUSION: This study provides preliminary evidence that an interaction between genetic susceptibilities (ie, TNF-2 carriers) and environmental factors (ie, bacterial vaginosis) is associated with an increased risk of spontaneous preterm birth.     

A single nucleotide A>G polymorphism at position -670 in the Fas gene promoter: relationship to preterm premature rupture of fetal membranes in multifetal pregnancies

OBJECTIVE: The relationship between a polymorphism at position -670 in the Fas gene (TNFRSF6) and preterm premature rupture of membranes (PPROM) in multifetal pregnancies was examined. METHODS: Buccal swabs from 119 mother-infant sets were analyzed for an adenine (A) to guanine (G) substitution at position -670 in the TNFRSF6 promoter. Pregnancy outcome data were subsequently obtained. Analysis was by Fisher exact test. RESULTS: Maternal allele G homozygosity (TNFRSF6*G) was observed in 42.4% of 33 PPROM pregnancies as opposed to 19.5% of 77 with no spontaneous preterm birth (P = .01). Similarly, TNFRSF6*G homozygosity was present in 37.5% of 32 first-born neonates from PPROM pregnancies as opposed to 18.7% of 75 uncomplicated pregnancies (P = .04). PPROM occurred in 8 of 14 (57.1%) pregnancies in which mother and all neonates were TNFRSF6*G homozygotes as opposed to 25 of 105 (23.8%) cases in which uniform TNFRSF6*G homozygosity was not observed (P = .02). CONCLUSIONS: A genetic variant in the Fas gene is associated with an increased rate of PPROM in multifetal pregnancies.     

Single-nucleotide polymorphisms in the KCNN3 gene associate with preterm birth

The objectives were to determine whether single-nucleotide polymorphisms (SNPs) in KCNN3 (encodes the small conductance calcium-activated potassium channel subfamily N, member 3), associate with preterm birth (PTB). In all, 602 preterm families with at least 1 preterm (<37 weeks gestation) infant were studied: DNA from the infant and one or both parents were genotyped for 16 SNPs in KCNN3. A region of interest within KCNN3 was sequenced in 512 Caucasian non-Hispanic mothers (412 with preterm deliveries;100 who delivered at term). Family-based association testing was used for genotyping analysis; Fisher exact test was used for sequencing analysis. Six SNPs (rs1218585, rs4845396, rs12058931, rs1218568, rs6426985, and rs4845394) were associated with PTB (all Ps < .05). These variations were all located within the intronic region between exons 1 and 2. Maternal sequencing revealed an association of 3 SNPs with spontaneous PTB; rs1218585 (P = .007), rs1218584 (P = .05), and a novel SNP at chromosome1:153099353 (P = .02). Polymorphisms in KCNN3 are associated with PTB and investigation into the functional significance of these allelic changes is warranted.     

Single nucleotide polymorphisms in the human progesterone receptor gene and spontaneous preterm birth

Progesterone supplementation can prevent preterm birth in some high-risk women. Progesterone binds to progesterone receptor (PR) and modulates the expression of target genes. This study investigates the association between single nucleotide polymorphisms (SNPs) in the PR gene and spontaneous preterm birth. DNA was extracted from consecutive patients with preterm birth (n = 78) and term controls (n = 415), and genotyping was performed for 3 PR SNPs (+331[G>A], + 770[C>T], +660[G>T]) using Sequenom matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Data were analyzed by chi(2) test and logistic regression analysis. Multivariate analysis showed no association between maternal carriage of minor + 331T, +770T, and/or +660T alleles and preterm birth when controlled for maternal age, ethnicity, gravidity, parity, prior preterm birth, route of delivery, or neonatal outcome. Carriage of +770T and +660T (but not +331T) was associated with preterm birth in women with a body mass index <18.5 kg/m(2) (relative risk, 10.8; 95% confidence interval, 1.4-82.6; P = .02). Maternal carriage of minor alleles of +331(G>A), +770(C>T), and +660(G> T) SNPs in the PR gene is not associated with spontaneous preterm birth.     

Polymorphism in intron 2 of the fetal interleukin-1 receptor antagonist genotype influences midtrimester amniotic fluid concentrations of interleukin-1beta and interleukin-1 receptor antagonist and pregnancy outcome

OBJECTIVE: Preterm labor in experimental models is initiated by intra-amniotic interleukin-1beta (IL-1beta) and inhibited by interleukin-1 receptor antagonist (IL-1ra). The IL-1ra gene is polymorphic and the different alleles are associated with variations in IL-1beta and IL-1ra production. The relationship among the IL-1ra genotype of the fetus, concentrations of IL-1beta and IL-1ra in second-trimester amniotic fluid, and pregnancy outcome was determined. STUDY DESIGN: Amniotic fluids from 291 consecutive women with singleton pregnancies, obtained at 15 to 17 weeks' gestation, were tested for IL-1beta and IL-1ra concentrations by enzyme-linked immunosorbent assay. DNA from fetal cells was analyzed for a length polymorphism in intron 2 of the IL-1ra gene by polymerase chain reaction. Pregnancy outcomes were obtained after completion of testing. RESULTS: The distribution of fetal IL-1ra genotypes was similar to that found in other populations: 50.9% (148) were homozygous for allele 1 (IL1RN*1), 39.5% (115) were IL1RN*1/allele 2 (IL1RN*2) heterozygotes, 6.9% (20) were IL1RN*2 homozygotes, whereas 2.7% (8) had combinations of other alleles. Fetal possession of IL1RN*2 was associated with a greater than 50% increase in midtrimester intra-amniotic IL-1beta levels (P=.006) and a smaller increase in IL-1ra levels (P=.01) compared with fetuses who were IL1RN*1 homozygotes. Despite the low sample size, IL1RN*2 homozygosity, but not midtrimester intraamniotic levels of IL-1beta and IL-1ra, was related to an increased rate of preterm birth (P<.0001). In the 11 pregnancies that were subsequently terminated because of major malformations, there was a decreased frequency of IL1RN*1 homozygosity (P=.04). Birth weight was unrelated to IL-1ra genotype. CONCLUSION: Possession by the fetus of the IL1RN*2 allele is associated with enhanced intraamniotic IL-1beta production. Induction of an intra-amniotic proinflammatory immune response might be more likely to lead to preterm labor in fetuses carrying the IL1RN*2 allele.     

Fetal interleukin-1 receptor antagonist gene polymorphism, intra-amniotic interleukin-1beta levels, and history of spontaneous abortion

OBJECTIVE: The purpose of this study was to determine whether fetal carriage of specific alleles of the polymorphic interleukin-1 receptor antagonist gene is associated with variations in intra-amniotic cytokine levels and previous pregnancy outcomes. STUDY DESIGN: Fetal cells in midtrimester amniotic fluid from 189 women were tested for interleukin-1 receptor antagonist intron 2 length polymorphisms. Concentrations of cytokines in amniotic fluid were tested by enzyme-linked immunosorbent assay. Pregnancy history data were obtained subsequently. RESULTS: Homozygosity for interleukin-1 receptor antagonist allele 1 was detected in 13 of 17 fetuses (76.5%) from women whose previous pregnancies all ended in spontaneous abortions, as compared with 33 of 74 fetuses (44.6%) from women with at least 1 previous term birth ( P = .02). Fetal carriage of interleukin-1 receptor antagonist allele 2 was associated with only 1 (5.9%) previous spontaneous abortion, as opposed to 31 pregnancies (41.9%) that were associated with a previous term delivery ( P = .004). A similar relationship between interleukin-1 receptor antagonist allele 1 and spontaneous abortions was observed when pregnancies of white women only were analyzed. Median mid trimester amniotic fluid interleukin-1beta concentrations were higher in women whose previous pregnancies ended in term deliveries (15.7 pg/mL), as opposed to women with 1 to 2 (6.4 pg/mL; P = .04) or > or =3 (4.1 pg/mL; P = .007) previous spontaneous abortions. Fetal carriage of interleukin-1 receptor antagonist allele 2 was associated with elevated intra-amniotic interleukin-1beta levels (16.2 pg/mL), as compared with interleukin-1 receptor antagonist allele 1 homozygotes (10.8 pg/mL; P = .03). CONCLUSION: Fetal carriage of interleukin-1 receptor antagonist allele 1 is associated with reduced intra-amniotic interleukin-1beta concentrations and an increased occurrence of spontaneous abortions in previous pregnancies.     

The Preterm Prediction Study: the value of serum alkaline phosphatase,alpha-fetoprotein,plasma corticotropin-releasing hormone,and other serum markers for the prediction of spontaneous preterm birth

OBJECTIVE: High levels of a number of analytes are found in maternal blood; alkaline phosphatase,alpha-fetoprotein, and corticotropin-releasing hormone have been associated with spontaneous preterm birth. We investigated the relationship between 8 potential blood markers and subsequent spontaneous preterm birth in asymptomatic pregnant women. STUDY DESIGN: We performed a nested case control study that involved 127 women who were enrolled in the preterm prediction study and who had a singleton spontaneous preterm birth at <35 weeks and 127 women who had a term birth and served as matched (age, parity, center) controls. Serum that was collected at 24 and 28 weeks was analyzed for alkaline phosphatase, alpha-fetoprotein, corticotropin-releasing hormone, and 5 other analytes. RESULTS: Alkaline phosphatase, alpha-fetoprotein, and corticotropin-releasing hormone, but not other analytes, were significantly elevated in pregnancies that ended in spontaneous preterm birth. For alkaline phosphatase at 24 weeks, the odds ratio for spontaneous preterm birth at <32 weeks was 6.8 (range, 1.4-32.8) and for spontaneous preterm birth at <35 weeks 5.1 (range, 1.7-15.6). Similar results were found at 28 weeks. For alpha-fetoprotein at 24 weeks, the odds ratio for spontaneous preterm birth at <32 weeks was 8.3 (range,2.2-30.9) and for spontaneous preterm birth at <35 weeks was 3.5 (range, 1.8-6.7). The levels at 28 weeks were still predictive but less so than at 24 weeks. Corticotropin-releasing hormone, at 28 weeks but not at 24 weeks, was predictive for spontaneous preterm birth at <35 weeks, with an odds ratio 3.4 (range, 1.0-10.9). CONCLUSION: Elevated alkaline phosphatase and alpha-fetoprotein are associated with subsequent spontaneous preterm birth in asymptomatic pregnant women at 24 and 28 weeks. Elevated corticotropin-releasing hormone levels at 28 weeks are associated with spontaneous preterm birth at <35 weeks.     

Polymorphism in intron 2 of the interleukin-1 receptor antagonist gene, local midtrimester cytokine response to vaginal flora, and subsequent preterm birth

OBJECTIVE: This study investigated the association between polymorphism in intron 2 of the interleukin-1 receptor antagonist gene, midtrimester vaginal microflora, vaginal interleukin receptor antagonist and interleukin-1beta levels and subsequent spontaneous preterm birth. STUDY DESIGN: Vaginal samples from 212 women, collected at 18-22 weeks' gestation, were analyzed for the polymorphism in intron 2 of the interleukin-1 receptor antagonist gene by polymerase chain reaction, qualitative and quantitative vaginal microflora, and interleukin-1beta and interleukin-1ra concentrations by enzyme-linked immunosorbent assay. Pregnancy outcome data were subsequently obtained. RESULTS: Carriage of intron 2 of the interleukin-1 receptor antagonist allele 2 (IL1RN * 2) was associated with an elevated vaginal pH in black ( P < .001) and white ( P = .005) women, a reduced interleukin-1beta response to anaerobic Gram-negative rods and/or Gardnerella vaginalis ( P < .01), and a decreased rate of spontaneous preterm deliveries (6% versus 18%, P = .02). In black women, IL1RN * 2 carriage was associated with increased anaerobic Gram-negative rods, Mycoplasma, and Peptostreptococci and decreased Lactobacilli colonization. CONCLUSION: IL1RN * 2 carriage was associated with a blunted proinflammatory interleukin-1beta response to abnormal vaginal flora. This property may decrease susceptibility to infection-related preterm birth.     

The very preterm infant - a population-based study

OBJECTIVES: The aim of this study was to assess perinatal risk factors and the survival of the very preterm infant in comparison with birth beyond 32nd birthweek, as well as health care utilization by mothers and infants in the Northern Health Region of Sweden. DESIGN: A population-based study was designed of all children (66,646) born in the Northern Health Region of Sweden during 1991-1996 and registered in the Swedish Medical Birth Registry. METHODS: Maternal and perinatal factors of infants born very preterm, that is, at < or =27 and 28-31 weeks of gestation, were analyzed for relative risk (RR), and a 95% confidence interval (CI), and compared with those of infants born 32-36 weeks of gestation. RESULTS: Of the 66,646 infants registered, 3,493 (5.2%) were born at 32-36 weeks, 394 (0.6%) at 28-31 weeks, and 199 (0.3%) at 22-27 weeks' gestation. No special socio-demographic maternal factors characterized these preterm births. The very preterm infants were more prone to perinatal complications such as premature rupture of the membranes (PROM) (RR=4.13; 95% CI=3.07-5.55), and both PROM and hemorrhage (RR=7.80; 95% CI=3.43-17.72). Infants born very preterm were more often twins, growth-retarded, malformed, and affected by sepsis and respiratory distress. There was significantly better survival of preterm infants born at < or =27 weeks' gestation if their mothers were given tertiary perinatal care. For infants born extremely preterm, survival tended to be better if they were delivered by cesarean section. CONCLUSION: The very preterm birth is more often than not a result of a complicated pregnancy. The infant is often sick before birth, and for its survival is highly dependent on the highest level of perinatal care.     

The contribution of birth defects to spontaneous preterm birth

The purpose of this study was to determine if and which birth defects (BDs) are risk factors for spontaneous preterm delivery, and to quantify that risk. A case-control study of spontaneously delivered term (n = 21,093) and preterm (n = 2937; 12.2%) liveborn neonates, between 1996 and 2000, at Ramón Sardá Maternity Hospital of Buenos Aires, was performed. Selected risk factors were compared between term and preterm neonates, and risks of preterm birth in the presence of BDs were evaluated, using stratified and logistic regression analyses. Preterm versus term neonates showed higher rates of most of the selected maternal and neonatal risk factors. The prevalence of BDs among preterm and term neonates was 4.1 and 2.0%, respectively (p < 0.001). Newborns with BDs showed a higher adjusted risk for preterm birth than those without BDs (odds ratio, 2.16; 95% confidence interval, 1.92 to 2.40), with the highest risks for skeletal dysplasias, abdominal wall defects, chromosome, multiple, and minor anomalies. That neonates with BDs are at risk for spontaneous preterm birth, regardless of other factors, should lead to a readjustment of health policies aimed at the reduction of preterm delivery.     

Lack of evidence that proline homozygosity at codon 72 of p53 and rare arginine allele at codon 31 of p21, jointly mediate cervical cancer susceptibility among Indian women

OBJECTIVES: The objective of this study was to identify whether variants of p53Arg72Pro and p21Ser31Arg were associated with increased risk for cervical cancer (CaCx), either independently or jointly, among Indian women. METHODS: Genotyping was done by PCR-RFLP using DNA from (i) 120 cervical biopsy tissues of squamous cell carcinoma of the cervix (of which 82 were HPV16/18 positive), and (ii) a total of 205 cytologically normal cervical scrapes (121 HPV-negative and 84 HPV16/18-positive samples, considered as discreet groups). Multiple logistic regression analyses were performed to examine additive or interactive effects of the two factors and for determining age-adjusted OR (95% CI) and P values. RESULTS: The observed association of proline homozygosity at codon 72 of p53 with CaCx infection (Bhattacharya, P., Duttagupta, C., Sengupta, S. 2002.Proline homozygosity in codon 72 of p53: A risk genotype for Human Papillomavirus related cervical cancer in Indian women. Cancer Lett 188: 207-211) was retained among Indian women harboring HPV16/18 (OR(age-adjusted) = 3.76; 95% CI = 1.03-13.80; P = 0.04). Significant independent association was evident between the p21 arginine allele (rare allele with frequency of 0.1) at codon 31 and CaCx, compared to HPV-negative cytologically normal controls (OR(age-adjusted) = 2.01; 95% CI = 1.00-4.06; P = 0.05). The two risk factors jointly failed to show statistical interaction towards susceptibility to CaCx. The p21 arginine allele was significantly associated with CaCx in the p53 proline non-homozygous group of subjects (OR(age-adjusted) = 2.68; 95% CI: 1.21-5.91; P = 0.01), and specifically in the p53 heterozygous group (OR(age-adjusted) = 2.91; 95% CI = 1.12-7.56; P = 0.03). CONCLUSIONS: p53 and p21 act in series in mediating cell cycle arrest. However, the two risk factors, p53 proline homozygosity and p21 arginine allele, although part of a common causal pathway, appear to act in a mutually exclusive manner.     

Association of polymorphisms in the beta2 and beta3 adrenoceptor gene with polycystic ovary syndrome

OBJECTIVE: To investigate polymorphisms of the beta2 and beta3 adrenoceptor (BAR-2 and BAR-3, respectively) genes associated with insulin-resistant polycystic ovary syndrome (PCOS) pathogenesis. STUDY DESIGN: Fifty-nine infertile Japanese women with PCOS and 97 healthy Japanese controls were studied. Blood metabolites and genomic DNA polymorphisms of BAR-2 (Arg16Gly and Gln27Glu) and BAR-3 (Trp64Arg) were analyzed. RESULTS: The PCOS group had significantly higher weight, body mass index, lipidemia and insulin resistance as compared to the control group. Glu 27 allele frequency in BAR-2 was significantly higher in PCOS patients as compared to the controls (0.07 vs 0.02, chi2 = 5.91, p = 0.02, OR 4.63, 95% CI 1.35-5.93), while Gly 16 allele frequency was only slightly higher in the PCOS group as compared to the controls (0.58 vs. 0.47, chi2 = 3.06, p = 0.08, OR 1.51, 95% CI 0.95-2.40). The Arg 64 allele frequency of BAR-3 was not significantly different between the 2 groups. Women with the Gly/Gly genotype for codon 16 or with either the Gln/Glu or Glu/Glu genotype for the codon 27 polymorphism of BAR-2 had significantly higher insulin resistance than those with the Arg/Arg and Gln/Gln genotypes. CONCLUSION: The polymorphism in codon 27 (Gln27Glu) of BAR-2 is linked to the expression of PCOS in Japanese women.     

Emotional Responses of Mothers of Late‐Preterm and Term Infants

ObjectiveTo compare the emotional responses of mothers of late‐preterm infants (34 0/7 to 36 6/7 weeks gestation) with those of mothers of full‐term infants.DesignA mixed method comparative study.SettingA southeastern tertiary academic medical center postpartum unit.ParticipantsSixty mothers: 29 mothers of late‐preterm infants and 31 mothers of full‐term infants.MethodsMeasures of maternal emotional distress (four standardized measures of anxiety, postpartum depression, posttraumatic stress symptoms, and worry about infant health) and open‐ended semistructured maternal interviews were conducted in the hospital following birth and by phone at one month postpartum.ResultsMothers of late‐preterm infants experienced significantly greater emotional distress immediately following delivery, and their distress levels continued to be higher at one month postpartum on each of the standardized measures. Mothers of late‐preterm infants also discussed the altered trajectories in their birth and postpartum experiences and feeling unprepared for these unexpected events as a source of ongoing emotional distress.ConclusionMothers of late‐preterm infants have greater emotional distress than mothers of term infants for at least one month after delivery. Our findings suggest that it may not be a single event that leads to different distress levels in mothers of late‐preterm and full‐term infants but rather the interaction of multiple alterations in the labor and delivery process and the poorer‐than‐expected infant health outcomes. In the future, researchers need to examine how and when mothers’ emotional responses change over time and how their responses relate to parenting and infant health and development.     

Primiparity: an 'intermediate' risk group for spontaneous and medically indicated preterm birth.

OBJECTIVE: Most women in their first pregnancy are at 'unknown' risk for preterm birth. We hypothesized that such women may be at an increased risk for preterm birth in comparison to those with a prior term birth. METHODS: We used Missouri's maternally-linked data (1989-97), comprised of women delivering their first singleton live birth (N = 259 431) and women delivering their first two consecutive singleton live births (N = 154 810). We compared preterm birth (<37 weeks) rates among women with a previous term birth, women with no reproductive history (primiparous women), and in those with a previous preterm birth. Risks of spontaneous and medically indicated preterm birth were also examined after adjustments for confounders through multivariate log-binomial regression models. RESULTS: Preterm birth rates were 8.1%, 9.6%, and 23.3% among women with a previous term birth, among primiparous women, and among those with a previous preterm birth, respectively. In comparison to women with a prior term birth, risks of spontaneous preterm birth among primiparous women and among women with a prior preterm birth were 1.1-fold (95% confidence interval (CI) 1.0, 1.2) and 2.5-fold (95% CI 2.4, 2.6) higher, respectively. These risks were higher for medically indicated preterm birth among both primiparous women (RR 1.3, 95% CI 1.2, 1.4) and those with a prior preterm birth (RR 3.2, 95% CI 3.0, 3.5) than for spontaneous preterm births. CONCLUSIONS: Primiparous women are at increased risk of both medically indicated and spontaneous preterm birth. The findings suggest that studies on preterm birth should consider a risk assignment to include three groups: low-risk (prior term birth), intermediate risk (primiparity), and high-risk (prior preterm birth). This strategy will be informative for the identification of women with impending risk of delivering preterm, and complications associated with prematurity.     

Use of oxytocin to prevent haemorrhage at caesarean section--a survey of practice in the United Kingdom

Objective

Preterm birth remains one of the most challenging areas in obstetrics. The pathogenesis of preterm labor is multifactorial and research on preterm birth has focused principally on infection and inflammatory markers. Recently the focus has turned to potential genetic factors influencing preterm birth. Uteroplacental insufficiency and thrombotic vasculopathy are considered part of the pathogenesis of preterm labor. Investigating the gene expression in the maternal/fetal interface seems of importance to expand our knowledge of the pathophysiology of preterm birth. The renin–angiotensin system (RAS) appears to play an important role in fetal/placental development and uteroplacental circulation. Hence, the aim of this study was to investigate angiotensin converting enzyme (ACE) activity and I/D polymorphisms in the ACE gene in mothers and infants with appropriately grown infants in relation to preterm birth and infant birth weight.

Study design

We conducted a cross-sectional study of 113 term pregnancies (≥37 weeks) and 18 preterm pregnancies (<37 weeks). Umbilical cord bloods (venous and arterial) were obtained from the placenta immediately after delivery for serum ACE activity, ACE genotype analysis of the I/D polymorphism and the acid-base status. Maternal venous samples were obtained just after delivery for analysis of ACE activity and ACE genotype.

Results

The distribution of the maternal ACE genotypes was similar for preterm and term births as was maternal ACE activity. Preterm infants were more likely to be of the DD genotype than term infants (7/18 (39%) vs. 11/83 (13%), p = 0.02) (adjusted p = 0.04). There was no correlation between ACE activity and birth weight (r² 0.00, p = 0.82).

Conclusions

These findings suggest that the ACE genotype of the infant may influence the risk of preterm birth among appropriately grown fetuses.