Mid-trimester Pregnancy Research Articles

Measurement of amniotic fluid interleukin-6 using commercial kits

Objective The association between increased amniotic fluid interleukin-6 (IL-6) concentrations and preterm labor has received increasing attention. Several research groups have evaluated this association using commercial IL-6 kits, which principally use the sandwich-enzyme-immunoassay method, and were originally created to measure IL-6 in plasma, serum, or culture media. We evaluated commercial kits for the determination of IL-6 in amniotic fluid. Methods Seven commercial kits were used to determine IL-6 concentrations in three amniotic fluid samples which were obtained from patients with clinical chorioamnionitis during labor and five from normal pregnancies at mid-trimester. Results Amniotic fluid IL-6 values differed significantly with some having over a 50-fold discrepancy and the recovery of known IL-6 added to amniotic fluid ranged from 12 to 123%. However, by all kits we were able to identify that amniotic fluid from patients with chorioamnionitis contained significantly higher IL-6 concentrations than those from normal mid-trimester pregnancies. Conclusion Our data indicate that standardization of the method for measuring IL-6 in amniotic fluid is desirable for the comparison of values from various laboratories. Infect. Dis. Obstet. Gynecol. 5:222–225, 1997. © 1997 Wiley-Liss, Inc.

Misoprostol versus concentrated oxytocin plus low-dose PGE 2 for mid-trimester pregnancy termination: A trial stopped

Misoprostol versus concentrated oxytocin plus low-dose PGE 2 for mid-trimester pregnancy termination: A trial stopped

Complications of midtrimester pregnancy termination: The effect of prior cesarean delivery

OBJECTIVE: Our purpose was to determine whether a prior cesarean delivery affects the incidence of complications in women having an indicated midtrimester medical pregnancy termination. STUDY DESIGN: A retrospective review of women who underwent a midtrimester medical termination of pregnancy from January 1980 to July 1995 ascertained obstetric history, uterotonic agent(s), and the occurrence of uterine rupture, blood transfusion, or curettage. The frequencies of maternal complications were compared in women with and without a prior cesarean section. RESULTS: Our study population included 606 women with a mean gestational age of 21.1 ± 3.1 weeks and a mean maternal age of 26.3 ± 7 years. Seventy-nine (13%) had undergone a prior cesarean section. There was no significant difference in the need for curettage between women with and without a prior cesarean section. However, there was an increased need for blood transfusions in women with a prior cesarean delivery (11.4% vs 5.3%, odds ratio 2.3, 95% confidence interval 1.1 to 5.0, p = 0.04). The incidence of uterine rupture was significantly higher among women with a prior cesarean (3.8% vs 0.2%, odds ratio 20.8, 95% confidence interval 14.1 to 104, p = 0.008). CONCLUSION: Our data suggest that a prior cesarean section is a risk factor for uterine rupture and blood transfusion in women having a midtrimester pregnancy termination. (Am J Obstet Gynecol 1996;175:889-92.)

Transabdominal Cervicoisthmic Cerclage in the Management of Recurrent Second Trimester Miscarriage and Preterm Delivery

Objective To evaluate the role of transabdominal cervicoisthmic cerclage (TCC) in the management of recurrent mid-trimester pregnancy miscarriage and preterm delivery. Design An observational study of 50 women with history of recurrent second trimester miscarriage and preterm delivery in whom TCC was performed. Setting A tertiary referral centre for high risk obstetrics. Results TCC was performed on 51 occasions in 50 women. One had TCC performed in two successive pregnancies. Prior to the procedure, they had experienced 36 first trimester miscarriages and 163 later pregnancy losses. These included 152 midtrimester miscarriages and 11 neonatal deaths after preterm delivery. There had been 4 survivors after preterm delivery. The total number of pregnancies after TCC was 61 with three women losing one pregnancy and subsequently having a successful pregnancy. Of these women 44 now have had a successful outcome. Six have not had a successful outcome. Eight women have had two successful consecutive pregnancies after TCC. The fetal survival was 85.2% post-procedure. Conclusions TCC is a procedure that may be used in a highly selected group of women with anatomical defects of the cervix and previous failed transvaginal cerclage resulting in recurrent second trimester pregnancy loss and preterm birth. Strict selection criteria were applied as TCC is an invasive procedure. Although TCC is not widely used our study suggests it may be the procedure to consider in women who have had recurrent second trimester pregnancy losses and preterm births associated with cervical damage.

Amniotic Fluid Alpha-fetoprotein Levels in Midtrimester Pregnancies

Objective The purpose of this study is to establish the normal levels of α-fetoprotein in amniotic fluid between 15 and 22 weeks of gestation. Method Amniotic fluid Alpha-fetoprotein(AFAFP)levels were measured by enzyme-immunoassy in pregnant women between 15 and 22 weeks of gestation for variety of indication of amniocentesis from October, 1994 to July, 1996 at Mokdong Hospital Ewha Womans University. The study group was selected from normal karyotype at prenatal genetic diagnosis and no congenital anomaly of fetus. Results The normal level of AFAFP was the highest at 16weeks and then it declined gradually as gestational weeks increased. The mean±SD levels of AFAFP from 15 to 22weeks were 16.9±5.7, 20.4±9.8, 13.8±6.8, 10.9±3.0, 8.1±2.3, 6.9±3.9, 5.6±1.6, 4.7±0.6µg/ml respectively, the median levels of AFAFP from 15 to 22weeks were 14.7, 16.2, 12.3, 11.0, 7.8, 5.5, 5.3, 4.8µg/ml, respectively. Conclusion We consider that this preliminary data normal AFAFP levels by each gestation weeks can be used as reference value for screening of anomalies or genetic disorder.

Enhanced twin pregnancy detection within an open neural tube defect and Down syndrome screening protocol using free-beta hCG and AFP.

We have applied our multimarker approach of maternal serum alpha-fetoprotein (AFP) and free-beta human chorionic gonadotropin (hCG) for Down syndrome screening to multiple gestations to assess its efficacy for improved detection of twin and triplet pregnancies. This study matched 225 cases of twin pregnancy and 39 cases of triplet pregnancy each with ten singleton pregnancies based on gestational week, race, time to receive sample, time of year of sample, and geographical area. The ratios of the MOM for each group at the tenth, 50th, and 90th percentiles were compared by the Wilcoxon test. Risks for twins were calculated using Bayes' rule, the age-related incidence of twins, and the levels of AFP and free-beta hCG. The tenth, 50th and 90th percentiles of free-beta hCG MOMs in twin and triplet cases were 0.85, 1.99, and 4.51, and 1.38, 2.78, and 4.07, respectively. For AFP, the MOMs at these percentiles were 1.26, 1.91, and 2.99, and 2.02, 2.68, and 5.30, respectively. The twin and triplet distributions for each marker were statistically significantly different from the singleton distributions (P < 0.0001) and from each other (P = 0.0012). At a twin risk cut-off of 1 in 50, 77.4 per cent of all twin gestations can be detected in a second-trimester AFP and free-beta hCG screening protocol with 5.1 per cent of singleton pregnancies falsely identified as at risk for twins. Our dual marker protocol for mid-trimester pregnancy screening combining AFP and free-beta hCG can identify over 77 per cent of twin pregnancies in women less than 35 years of age. This benefit may contribute to an improved outcome of pregnancy by early detection of multiple gestation.

Normal nuchal thickness inthe midtrimester indicates reduced risk of Down syndrome in pregnancies with abnormal triple-screen results

OBJECTIVE: Our purpose was to determine whether nuchal thickness measurement can identify the euploid fetuses in midtrimester pregnancies at increased risk for Down syndrome on the basis of maternal age and serum screening. STUDY DESIGN: Nuchal thickness was obtained prospectively in 651 consecutive fetuses at 14 to 21 weeks' gestation and at ≥1:270 risk for Down syndrome on the basis of unconjugated estriol, α-fetoprotein, and human chorionic gonadotropin levels. The risk of Down syndrome with a normal nuchal thickness was determined. A receiver-operator characteristic curve was used to determine a serum-based risk threshold below which the risk of Down syndrome was low. The prevalence of Down syndrome in fetuses with both a normal nuchal thickness and a below-serum-risk threshold was compared with prevalence in either those above threshold risk or with an abnormal nuchal thickness. RESULTS: There were eight cases of trisomy 21 and one case each of 46, XX 47, XXX , 46, XY 47, XY , + 7, and 46,XX,11q−. The sensitivity of an abnormal nuchal thickness (≥6 mm) for detecting Down syndrome was four ineight (50%) (95% confidence interval 15.3% to 84.6%). The risk of Down syndrome was significantly increased with an abnormal compared with a normal nuchal thickness, four in 13 (30.8%) versus four in 638 (0.6%), p < 0.0001. A risk threshold was defined at ≥1:100 on the basis of the receiver-operactor characteristic plot. Of 390 cases with a normal nuchal thickness and a serum risk estimate <1:100, there were no cases of Down syndrome ( 0 390 vs 8 253 , p = 0.002 ). CONCLUSION: Normal nuchal thickness significantly reduces the risk of Down syndrome and may help reduce the number of amniocenteses done for abnormal triple screen results.

Second Trimester Uterine Atony Imitating Ectopic Pregnancy: Magnetic Resonance Diagnosis

When an obstetrical patient was referred for inability to auscultate fetal heart tones at 18 weeks' gestation, ultrasound identified a single living fetus in the maternal right upper quadrant. Magnetic resonance imaging (MRI) ruled out a suspected uterine ectopic pregnancy and avoided laparotomy. The patient experienced an uncomplicated term delivery. MRI is a useful adjunct to ultrasound for mid-trimester pregnancy localization when the differential diagnosis includes uterine eccyesis.

Transabdominal cervicoisthmic cerclage in the management of recurrent second trimester miscarriage and preterm delivery

To evaluate the role of transabdominal cervicoisthmic cerclage (TCC) in the management of recurrent mid-trimester pregnancy miscarriage and preterm delivery. An observational study of 50 women with history of recurrent second trimester miscarriage and preterm delivery in whom TCC was performed. A tertiary referral centre for high risk obstetrics. TCC was performed on 51 occasions in 50 women. One had TCC performed in two successive pregnancies. Prior to the procedure, they had experienced 36 first trimester miscarriages and 163 later pregnancy losses. These included 152 midtrimester miscarriages and 11 neonatal deaths after preterm delivery. There had been 4 survivors after preterm delivery. The total number of pregnancies after TCC was 61 with three women losing one pregnancy and subsequently having a successful pregnancy. Of these women 44 now have had a successful outcome. Six have not had a successful outcome. Eight women have had two successful consecutive pregnancies after TCC. The fetal survival was 85.2% post-procedure. TCC is a procedure that may be used in a highly selected group of women with anatomical defects of the cervix and previous failed transvaginal cerclage resulting in recurrent second trimester pregnancy loss and preterm birth. Strict selection criteria were applied as TCC is an invasive procedure. Although TCC is not widely used our study suggests it may be the procedure to consider in women who have had recurrent second trimester pregnancy losses and preterm births associated with cervical damage.

Clinical Usefulness of the Dye‐Injection Method for Diagnosing Premature Rupture of the Membranes in Equivocal Cases

In 1981, we preliminarily reported on the clinical value and safety of the intra-amniotic dye (Phenol-sulfonphthalein, PSP)-injection method for diagnosing PROM. In the current study, through examination of 64 equivocal cases in the midtrimester of pregnancy, we investigated the clinical efficacy of the PSP test. In the present study we examined patients with equivocal PROM in their 14th week to 33rd week of gestation, whose findings were positive according to a combination of conventional diagnostic methods. The results of the PSP test and conventional diagnostic methods were compared with the final diagnosis of PROM. The conventional diagnostic methods showed an accuracy rate of 63.9%-70.5%, in contrast to the PSP test, which had a 100%-accuracy rate (p < 0.001). Using the PSP test in combination with amnioscopy, we have established a method of differentially diagnosing PROM. We have reconfirmed the clinical efficacy of the PSP test in 64 equivocal PROM cases.

Antibodies to ureaplasma urealyticum in women with intraamniotic infection and adverse pregnancy outcome

To determine the association between antibody response to Ureaplasma urealyticum and pregnancy outcome in women with ureaplasmal invasion of the amniotic cavity. A cross section study was performed in our high risk pregnancy unit. Three groups of pregnant women were identified: 1) 271 women at the midtrimester of pregnancy (16-20 weeks), who underwent transabdominal amniocentesis for genetic indications 2) 161 consecutive women admitted with preterm labor and intact membranes. 3) 118 consecutive patients with preterm premature rupture of membranes. Amniotic fluids were cultured for Ureaplasma urealyticum, Mycoplasma hominis and also for other aerobic and anaerobic bacteria. Serum antibodies to Uu were measured by a specific enzyme-linked-immunosorbent-assay. The prevalence of positive AF cultures with Uu in the 3 study groups was 2.9%, 4.3% and 17.8%, and the prevalence of antibodies to Uu in the AF-colonized patients was 50%, 86% and 57%, respectively. Adverse pregnancy outcome (preterm birth, low birth weight or fetal death) among all AF colonized women, was significantly higher in patients with antibodies to Uu than in those without antibodies; preterm delivery 90% vs. 43%, and low birth weight infants or fetal death 85% vs. 28%, p = 0.006 and 0.001 respectively. Women with intraamniotic infection with Uu and elevated levels of antibodies to Uu, had a higher rate of preterm delivery, and low birthweight infants/fetal death than those without antibody to Uu.

Intravaginal Misoprostol for Termination of Midtrimester Pregnancy

Misoprostol seems to be a drug with many potential uses apart from the treatment of gastric and duodenal ulcers. The oral tablet appears to be effective for termination of midtrimester pregnancy when administered intravaginally. Further research should be carried out to determine its full range of action in order that the drug can be utilized to its maximum potential.

Ureaplasma urealyticum cervical colonization as a marker for pregnancy complications

Objectives: To determine the clinical significance of cervical colonization with ( Ureaplasma urealyticum (Uu) and its possible relationship to pregnancy outcome. Methods: Cervical cultures for Uu and serum antibodies to Uu were determined in four groups of pregnant women: (1) 117 women who underwent mid-trimester amniocentesis; (2) 47 women with preterm labor and intact membranes; (3) 34 women with preterm premature rupture of membranes; and (4) a control group of 315 healthy women with normal pregnancies. Statistical methods used were the chi-square and Fisher's exact tests. Results: A significant increase in the cervical colonization rate with Uu was detected in all study groups (62%, 77% and 74%, respectively) when compared with the control group (42%). Women at mid-trimester of pregnancy with a positive cervical culture and high levels of antibodies, had a higher rate of pregnancy complications than those with a negative culture and absence of antibodies (62 vs. 28%, respectively; P = 0.0006). Conclusion: Cervical colonization with Uu when associated with elevated titers of antibodies to Uu, may serve as a marker for the identification of a subpopulation of women who are at high risk for the development of pregnancy complications.

Mid-trimester pregnancy termination: Concentrated oxytocin plus low-dose PGE 2 versus standard dose PGE 2: [formula omitted], J.C. Hauth, T. Lincoln, x K. Savage x. Dept. of OB/GYN University of Alabama at Birmingham, Birmingham, AL

Mid-trimester pregnancy termination: Concentrated oxytocin plus low-dose PGE 2 versus standard dose PGE 2: [formula omitted], J.C. Hauth, T. Lincoln, x K. Savage x. Dept. of OB/GYN University of Alabama at Birmingham, Birmingham, AL

Conservative management of severe chronic hypertension in pregnancy

Severe chronic hypertension in pregnancy is a condition frequently associated with poor maternal and fetal outcome. Meticulous antenatal care can lead to a reduction in morbidity and mortality. The case described is that of a primigravida who presented with severe chronic hypertension in the midtrimester of pregnancy. She was treated with four antihypertensive drugs and aspirin, and a favourable pregnancy outcome was achieved.

Optimal nuchal skin-fold thresholds based on gestational age for prenatal detection of Down syndrome

We attempted to determine optimal nuchal skin-fold thresholds throughout the second trimester of pregnancy for the detection of Down syndrome. Thresholds of 5, 6, and 7 mm were prospectively tested in 8138 consecutive midtrimester pregnancies. The pregnancies were divided into early (14 to 18 weeks) and late (19 to 24 weeks) second-trimester time frames. The pregnancies were also subdivided by maternal age, and the same thresholds were tested for efficacy in the women < 35 years old versus those > or = 35 years old. There were a total of 32 fetuses with trisomy 21 in the study population. From 14 to 18 weeks' gestation, a nuchal fold thickness of > or = 5 mm was the optimal threshold. Measurements of this magnitude were found in 2.9% of pregnancies and produced a sensitivity of 42% (11/26) for the detection of Down syndrome. When adjusted for the incidence of Down syndrome in the general population, the 5 mm threshold had a positive predictive value of 1 in 48. In the 19 to 24 week gestational time frame, > or = 6 mm appeared to be the optimal threshold, yielding a positive screen rate of 3.7% with a sensitivity of 83% (5/6). The adjusted positive predictive value was 1 in 38. The sensitivity of nuchal skin-fold thickness for Down syndrome detection was similar in women < 35 and > or = 35 years old. Positive predictive value was better in the women > or = 35 years old because of the higher prevalence of affected fetuses in this group. Whereas definitive diagnostic testing should still be offered to all women with risk factors for a fetus with trisomy 21, differential nuchal skin-fold thresholds based on gestational age are effective for the detection of Down syndrome in pregnancies at low risk.

Macrophage Inflammatory Protein‐1α in Term and Preterm Parturtition: Effect of Microbial Invasion of the Amniotic Cavity

This study was conducted to determine whether: (1) gestational age, parturition, and microbial invasion of the amniotic cavity (MIAC) are associated with changes in amniotic fluid concentrations of immunoreactive macrophage inflammatory protein-1 alpha; (2) amniotic fluid concentrations of macrophage inflammatory protein-1 alpha are correlated with the white blood cell count and the concentrations of interleukin-8 in amniotic fluid. Amniotic fluid was retrieved by amniocentesis from 126 patients; 54 women with preterm labor and intact membranes (no MIAC-delivery at term, N = 21; no MIAC-preterm delivery, N = 16; MIAC-preterm delivery, N = 17); 62 patients at term (no labor, N = 19; labor-no MIAC, N = 20; labor-MIAC, N = 23); and 10 patients in the midtrimester of pregnancy. Amniotic fluid was cultured for aerobic, anaerobic and Mycoplasma species. Determinations of amniotic fluid macrophage inflammatory protein-1 alpha and interleukin-8 were performed with immunoassays validated for amniotic fluid (sensitivity: 14.2 pg/ml and 0.3 ng/ml, respectively). Kruskal-Wallis analysis of variance (ANOVA) for censored data, Mann-Whitney U test and Spearman's rank correlation were performed for analysis. 1) Amniotic fluid macrophage inflammatory protein-1 alpha was present in only 31.0% (9/29) of patients not in labor (midtrimester and term). 2) Patients with preterm labor and MIAC had higher amniotic fluid concentrations of macrophage inflammatory protein-1 alpha than those without MIAC (no MIAC-delivery at term: median 0.0 pg/ml, range 0.0-221.2; no MIAC-preterm delivery: median 37.4 pg/ml, range 0.0-494.6; MIAC-preterm delivery: median 7171.0 pg/ml, range 402.5-37994.0; P < 0.00001). 3) Among patients at term, MIAC was associated with higher concentrations of amniotic fluid macrophage inflammatory protein-1 alpha than patients without MIAC (no labor: median 0.0 pg/ml, range 0.0-25.6; labor-no MIAC: median 16.7 pg/ml, range 0.0-161.6; labor-MIAC: median 103.8 pg/ml, range 0.0-4349.0, P < 0.001). 4) Among patients in preterm labor, a strong correlation was found between amniotic fluid concentrations of macrophage inflammatory protein-1 alpha and interleukin-8 (r = 0.9, P < 0.00001) and between amniotic fluid macrophage inflammatory protein-1 alpha concentrations and amniotic fluid white blood cell count (r = 0.6, P < 0.0001). (1) Macrophage inflammatory protein-1 alpha is undetectable in most amniotic fluid samples from patients in the midtrimester of pregnancy and at term not in labor. (2) Microbial invasion of the amniotic cavity is associated with increased concentrations of immunoreactive amniotic fluid macrophage inflammatory protein-1 alpha in both term and preterm gestations. (3) Amniotic fluid macrophage inflammatory protein-1 alpha concentrations significantly correlate with interleukin-8 levels and white blood cell count in amniotic fluid. Our data strongly suggest a role for macrophage inflammatory protein-1 alpha in the mechanisms responsible for the recruitment of leukocytes into the amniotic cavity during the course of intrauterine infection.

Safety of midtrimester pregnancy termination by laminaria and evacuation in patients with previous cesarean section

The objective of this study was to retrospectively assess whether there was an increased perioperative risk in midtrimester pregnancy termination by laminaria and evacuation associated with a previous uterine scar. From 1978 to 1993 1064 patients underwent midtrimester (14 to 22 weeks) pregnancy termination by means of laminaria and evacuation. Of these, 70 patients had a previous uterine scar and are the subjects of this study. There were no major operative complications, such as anesthetic complications, perforations, or cervical lacerations, in the entire series. Mean operative time (minutes) for induced abortion was statistically similar in the unscarred compared with the scarred uteri groups (8.03 +/- 4.40 vs 7.46 +/- 4.42, respectively) and was statistically different when the indication for evacuation was missed abortion (6.08 +/- 1.86 vs 4.81 +/- 2.11, respectively; p < 0.005). This difference in operative time could be explained by the number of laminaria tents used in each group. Atony with hemorrhage occurred in two patients who underwent induced abortion, and disseminated intravascular coagulation occurred in eight missed abortion cases, but none had scarred uterus. Previous cesarean section scar does not seem to increase the perioperative risk of late termination (14 to 22 weeks) by the laminaria and evacuation technique.

Rat embryo culture to detect nutritional deficiency in women with poor reproductive histories

The cause of habitual early pregnancy loss is not known for most affected couples. It has been proposed that a deficiency of amino acids or other nutrients may contribute to early embryo loss, and an assay based on culture of rat embryos in human serum has been proposed to evaluate women with poor reproductive histories. We tested this assay in women with unexplained infertility ( n = 27), habitual abortion ( n = 15), and normal midtrimester pregnancies ( n = 10) by examining the ability of subject's serum to support the normal development of rat embryos in culture with and without supplemental vitamins and amino acids. Nonpregnant women with nutrient deficiencies identified in this manner were given oral supplements or placebo and were retested. A similar proportion of women in each group had serum that was unable to support the normal development of rat embryos without supplemental vitamins and amino acids. When oral supplements were used, most sera were able to support normal embryo growth. There were no seroconversions on placebo. In spite of the apparent success in producing seroconversions on oral supplementation, only two women conceived, one on the placebo treatment and one on nutritional supplements. Because serum nutrient deficiencies identified by rat embryo culture could not distinguish normal pregnant women from women with unexplained infertility or habitual abortion, and because of the low pregnancy rates, we could not confirm the utility of this assay for the general population of women with habitual abortion. If subtle nutritional deficiencies play a role in early pregnancy loss, it may require a more homogeneous population of women with, for example, a history of five or more spontaneous pregnancy losses.

Randomized trial of intraumbilical vein oxytocin in midtrimester pregnancy losses

The purpose of this double-blind prospective randomized trial was to determine whether high-dose intraumbilical vein oxytocin injection shortens the third stage of labor in midtrimester pregnancy losses. Patients (n = 50) with spontaneous or induced midtrimester pregnancy losses (14 to 26 weeks' gestation) were randomized to receive either 100 IU of oxytocin in 20 ml of normal saline solution or 20 ml of normal saline solution alone as a placebo. The umbilical vein was injected as soon as the cord was clamped. Outcome data were collected. Of the 50 patients randomized, 45 completed the study. Five were excluded after randomization because of either cesarean delivery (1 patient) or en caul delivery (4 patients). Twenty-one patients received oxytocin, and 14 received placebo. Ten patients who were not injected because of technical failure were evaluated separately. There were no differences between the three groups with regard to gestational age, fetal weight, length of the third stage, blood loss, or need for operative removal of the placenta. Injection of high-dose oxytocin into the umbilical vein in second-trimester pregnancy losses does not shorten the third stage of labor or decrease the need for surgical intervention because of retained placenta.