Association of a maternal CD14 -159 gene polymorphism with preterm premature rupture of membranes and spontaneous preterm birth in multi-fetal pregnancies.

CD14, the major receptor for bacterial lipopolysaccharide (LPS) as well as other microbial antigens, is a component of the innate immune system. We hypothesized that a single nucleotide C>T polymorphism at position -159 in the CD14 gene that results in elevated CD14 production would influence susceptibility to preterm premature rupture of membranes (PPROM) and spontaneous preterm birth (SPTB) in multi-fetal pregnancies. DNA from 107 mother-twin and three mother-triplet pairs was analyzed. Pregnancy outcomes were obtained after completion of testing. CD14*T homozygosity was present in 39.3% of 28 women whose pregnancies ended with PPROM, as opposed to 18.1% of 72 pregnancies without a SPTB (P=0.03). There was no relation between the fetal CD14 genotype and PPROM. The likelihood ratio (LR) for PPROM was 2.2 for women homozygous for CD14*T. The LR increased to 3.3 and 3.6 if the CD14 polymorphism was present in combination with previously determined maternal polymorphisms in the genes coding for the inducible 70kDa heat shock protein (hsp70-2) and the interleukin-1 receptor antagonist (IL1RN), respectively. Thus, an enhanced maternal pro-inflammatory immune response to LPS may increase susceptibility to PPROM in multi-fetal pregnancies.

Obstetric outcomes after surgical abortion at > or = 20 weeks' gestation.

OBJECTIVE: The purpose of this study was to describe obstetric outcomes after surgical abortion at > or = 20 weeks, and to identify risk factors for subsequent spontaneous preterm birth. STUDY DESIGN: Patients who had surgical abortion at > or = 20 weeks' gestation from 1996 to 2003 and received subsequent prenatal care at The New York Weill Cornell Medical Center were identified. Indication for abortion, operative technique, and subsequent pregnancy outcomes were reviewed. Student t test, Fisher exact test, and Mann-Whitney U were used where appropriate. RESULTS: One hundred and twenty pregnancies in 89 women were identified. Thirteen (10.8%) ended with early miscarriage, and 5 were electively terminated. Of the remaining 102 pregnancies, 7 ended with spontaneous preterm birth. Those who experienced preterm birth were more likely to have undergone abortion due to cervical dilation and/or preterm premature rupture of membranes (PPROM) (27.3% vs 4.4%; P = .03). Those with a multifetal pregnancy in the subsequent pregnancy were more likely to have preterm birth (75.0% vs 4.3%; P < .001). In patients who underwent dilation and evacuation (D&E) for reasons other than cervical dilation and/or PPROM, rates of spontaneous preterm birth were identical between those who had intact dilation and extraction (D&X) and D&E using forceps (4.2% vs 4.5%; P = 1.0). CONCLUSION: In those who have undergone D&E at > or = 20 weeks, only a history of midtrimester cervical dilation and/or PPROM or a current multifetal pregnancy were associated with 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.

Polymorphisms in the tumor necrosis factor-alpha gene at position -308 and the inducible 70 kd heat shock protein gene at position +1267 in multifetal pregnancies and preterm premature rupture of fetal membranes.

OBJECTIVE: The purpose of this study was to determine the relationship between preterm premature rupture of membranes, tumor necrosis factor-alpha, and heat shock protein-70 gene polymorphisms in multifetal gestations. STUDY DESIGN: Buccal swabs from 101 mother-neonate pairs of multifetal pregnancies were tested for single nucleotide polymorphisms at position -308 of the tumor necrosis factor-alpha gene and +1267 of the heat shock protein-70 gene. Pregnancy outcome data were obtained subsequently. RESULTS: Tumor necrosis factor-alpha allele 2 carriage by the first-born occurred in 10 of 27 pregnancies (37.0%) that resulted in preterm premature rupture of membranes compared with 6 of 67 pregnancies (9.0%) without preterm premature rupture of membranes ( P = .002). The allele frequency of tumor necrosis factor-alpha allele 2 and heat shock protein-70 allele 2 in the first born was higher in pregnancies that were complicated by preterm premature rupture of membranes (18.5% vs 4.5%; P = .003; and 57.7% vs 41.3%; P = .04, respectively). There was no relationship between tumor necrosis factor-alpha allele 2 or heat shock protein-70 allele 2 carriage by the second fetus or mother and preterm premature rupture of membranes. CONCLUSION: Tumor necrosis factor-alpha allele 2 and/or heat shock protein-70 allele 2 carriage by the first-born fetus is associated with preterm premature rupture of membranes in multifetal pregnancies.

Clinical significance of first trimester crown-rump length disparity in dichorionic twin gestations.

OBJECTIVE: The purpose of this study was to determine the clinical significance of first trimester crown-rump disparity in dichorionic twin gestations. STUDY DESIGN: Ultrasound examinations of dichorionic twin pregnancies between 11 and 14 weeks of gestation were evaluated for growth discordance using crown-rump length. Medical records were reviewed for antenatal complications that included spontaneous abortion, fetal death, fetal structural or chromosomal anomalies, and preterm delivery. Fisher's exact test was used for statistical analysis; a probability value of <.05 was considered significant. RESULTS: Of 159 twin pregnancies, there were 7 fetal structural anomalies, 2 fetal chromosomal anomalies, 5 second-trimester spontaneous abortions, 3 second-trimester fetal deaths, and 1 third-trimester fetal death. Pregnancies that were complicated by fetal structural or chromosomal anomalies had significantly greater median crown-rump length discordance than pregnancies without fetal anomalies (4.0 mm vs 2.0 mm; P = .02). Crown-rump length discordance >10%, which is the 90th percentile for intertwin crown-rump length disparity in our population, was associated with a significantly higher incidence of fetal anomalies (22.2% vs 2.8%; P = .01). CONCLUSION: First trimester crown-rump length disparity in dichorionic twin gestations is associated with an increased risk of fetal structural and chromosomal anomalies.

First- and second-trimester ultrasound assessment of gestational age.

OBJECTIVE: The purpose of this study was to evaluate and compare the accuracy of first- and second-trimester ultrasound assessment of fetal age. STUDY DESIGN: Differences between ultrasound estimated gestational age and true gestational age were calculated between 11 to 14 weeks of gestation and 18 to 22 weeks of gestation for singleton, twin, and triplet pregnancies that were conceived by in vitro fertilization. RESULTS: One hundred four singleton pregnancies, 81 twin pregnancies, and 33 triplet pregnancies were included. First trimester ultrasound estimates overestimated gestational age by a mean (+/- SEM) of 1.3 +/- 0.2 days (P < .0001) for singleton pregnancies, 1.4 +/- 0.2 days (P < .0001) for twin pregnancies, and 0.8 +/- 0.4 days (P = .027) for triplet pregnancies. Second trimester estimates were underestimated by a mean of -0.1 +/- 0.4 days (P = .87) for singletons, -0.6 +/- 0.3 days (P = .083) for twins, and -0.6 +/- 0.5 days (p = 0.21) for triplets. CONCLUSION: Ultrasound assessment of gestational age is very accurate and is marginally better in the first trimester compared with the second.

Intrapartum elective cesarean delivery: a previously unrecognized clinical entity.

OBJECTIVE: The purpose of the study was to investigate the incidence of intrapartum patient choice cesarean delivery-patients' requesting cesarean delivery and physicians' offering it during labor-and factors possibly influencing these requests and offers. METHODS: For a 6-month period from May 1, 2002, to October 31, 2002, obstetricians were asked to complete a questionnaire after all intrapartum cesarean deliveries regarding whether cesarean delivery was offered by the obstetrician or requested by the patient before being medically indicated. Patient medical records and physician demographic information were reviewed. RESULTS: There were 422 cases that met inclusion criteria. Questionnaires were completed in 100% of cases. Cesarean delivery was offered in 13% before a clear medical indication and requested in 8.8%. Older obstetricians, maternal-fetal medicine specialists, and full-time faculty were significantly more likely to offer cesarean delivery (P =.009, P <.001, and P =.015, respectively). Patients who were unmarried or undergoing labor induction were less likely to request cesarean delivery (P =.029 and P =.035, respectively). Maternal age, parity, stage or length of labor, epidural use, gestational age, insurance status, day of week, and time of delivery did not affect whether patients requested or were offered cesarean delivery. CONCLUSION: This study documents a heretofore unrecognized clinical entity: intrapartum elective cesarean delivery. Physician characteristics, as opposed to patient characteristics or intrapartum factors, are a major determinant of whether laboring patients are being offered cesarean delivery. LEVEL OF EVIDENCE: III

Dilation and evacuation at >or=20 weeks: comparison of operative techniques.

OBJECTIVE: The objective of this study is to compare the relative safety of 2 techniques for surgical abortion late in the second trimester.Study design Retrospective review of patients who underwent surgical abortion at >or=20 weeks' gestation at our hospital from June 1996 through June 2003. Records were reviewed to determine whether the technique used was dilation and evacuation or intact dilation and extraction. Subsequent pregnancies at our hospital were identified, and obstetric outcomes were recorded. Categorical data were compared with Fisher exact test and chi(2) analysis. Continuous data were compared with Mann-Whitney U test. RESULTS: Three hundred eighty-three patients met inclusion criteria. Intact dilation and extraction was performed in 120 cases, and dilation and evacuation was used in 263. Intact dilation and extraction was associated with higher parity, later gestational age, and more preoperative cervical dilation. There was no difference in procedure time or estimated blood loss in the 2 groups. Complications occurred in 19 cases (5.0%), and occurred with similar frequency in the 2 groups. We identified 62 subsequent pregnancies. There were no second-trimester miscarriages. Spontaneous preterm birth occurred in 2 of 17 (11.8%) pregnancies in the intact dilation and extraction group, compared with 2 of 45 (4.4%) in the dilation and evacuation group (P=.30). CONCLUSION: Outcomes appear similar between patients undergoing dilation and evacuation and intact dilation and extraction after 20 weeks' gestation. Subsequent obstetric outcomes are similar between the 2 groups. The technique for surgical abortion should be determined by the physician on the basis of intraoperative factors.

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.

Interleukin-1 receptor antagonist gene polymorphism and multifetal pregnancy outcome.

OBJECTIVE: The purpose of this study was to determine whether interleukin-1 receptor antagonist and/or interleukin-1beta gene polymorphisms influence multifetal pregnancy outcome. STUDY DESIGN: Maternal and neonatal buccal swabs from 51 multifetal gestations were analyzed for interleukin-1 receptor antagonist and interleukin-1beta alleles. Outcome data were obtained subsequently. RESULTS: Fetal carriage of interleukin-1 receptor antagonist allele 1 was more than twice as prevalent as the carriage of allele 2. Preterm premature rupture of membranes was observed in 12 of 24 pregnancies (50.0%) in which 2 fetuses tested positive for interleukin-1 receptor antagonist allele 2, as opposed to only 3 of 27 pregnancies (11.1%) in which 1 or neither fetus tested positive for interleukin-1 receptor antagonist allele 2 (P=.005). Similarly, 20 of 26 neonates (76.9%) with documented morbidity tested positive for interleukin-1 receptor antagonist allele 2, as compared with 36 of 78 neonates (46.2%) without morbidity (P=.007). Fetal or maternal interleukin-1beta polymorphisms or maternal interleukin-1 receptor antagonist polymorphisms were unrelated to pregnancy outcome. CONCLUSION: Fetal carriage of interleukin-1 receptor antagonist allele 2 was associated with both preterm premature rupture of membranes and neonatal morbidity in women with multifetal pregnancies.

First trimester prediction of growth discordance in twin gestations.

OBJECTIVE: The purpose of this study was to determine whether first trimester ultrasound scanning can identify twin gestations that are at risk for subsequent growth discordance. STUDY DESIGN: Ultrasound examinations of dichorionic twin pregnancies between 11 and 14 weeks of gestation were evaluated for growth discordance with crown-rump length. Pregnancies that were complicated by fetal death or anomalies were excluded from the analysis. Birth weight discordance was defined as >or=20% difference in birth weight, relative to the larger twin. Fisher's exact, Mann Whitney U, and Spearman rho tests were used for statistical analysis. RESULTS: Of 130 twin pregnancies, 16 pregnancies (12.3%) had discordant birth weight. Crown-rump length disparity was correlated positively with birth weight discordance (r=0.31; P<.001). Of pregnancies with a discrepancy of 3 days discrepancy (P=.004), which resulted in a likelihood ratio of 5.9 for having discordant birth weight. CONCLUSION: Twins who are ultimately discordant at birth may exhibit differences in growth as early as 11 to 14 weeks of gestation.