Outcomes for subsequent pregnancy in women who have undergone misoprostol mid-trimester termination of pregnancy

In Australia, the most common method of mid-trimester termination of pregnancy (TOP) is by medical induction with the prostaglandin E 1 analog misoprostol. This study was undertaken to compare the pregnancy outcomes of women who had undergone a misoprostol mid-trimester TOP in their last pregnancy with those of a similar cohort of women without a history of misoprostol TOP. This study suggests a possibility that medical mid-trimester TOP with misoprostol increases the risk of preterm or very preterm delivery in a subsequent pregnancy but larger studies are needed to confirm or dismiss this.     

Management of cervical weakness based on the measurement of cervical resistance index

OBJECTIVE: To assess the value of measuring cervical resistance index (CRI) as an aid to selecting patients with a history of spontaneous mid-trimester miscarriage for cervical cerclage in subsequent pregnancies. STUDY DESIGN: An observational study of 175 patients with a history of one or more spontaneous mid-trimester losses and 123 non-pregnant women who had CRI measurements performed while undergoing routine gynaecological surgery. Those women whose CRI indicated an incompetent cervix were recommended for cervical cerclage in future pregnancies while women with a normal CRI were recommended for conservative management without cerclage. RESULTS: The median CRI in the 123 control women was 38.26 N while the median CRI in the study group was 17.00 N. In 62 of the 175 study women (35%) the CRI findings were at variance with the history of previous mid-trimester loss; 30 (16.6%) were deemed competent on CRI whereas the history suggested incompetence and 32 (18.4%) were incompetent on CRI while the history suggested that the cervix should be competent. The 175 study women had had 486 previous pregnancies with a successful outcome in 27.4% of the pregnancies. Ninety-four patients have now had 148 pregnancies with a successful outcome in 75.8% of the pregnancies. CONCLUSIONS: Non-pregnant women with a history of spontaneous mid-trimester miscarriage have a significantly lower cervical resistance index than parous women who have not suffered mid-trimester loss. In 35% of patients the CRI was at variance with the history of the previous loss. CRI may be a useful technique to aid the diagnosis of cervical weakness allowing a rational selection for treatment with prophylactic cervical cerclage.     

Chorioamnionitis and mid-trimester pregnancy loss

Mid-trimester pregnancy loss defined as miscarriage at 14-23 weeks' gestation and preterm birth between 24 and 28 weeks are in essence clinical manifestations of the same disease process. The pathogenic and socio-biologic risk factors are the same, but the timing of onset of uterine activity and cervical dilatation may be delayed in the case of preterm birth. The overwhelming majority of cases are associated with ascending infection from the lower genital tract. Women with a prior history of late miscarriage are at increased risk of preterm delivery and vice versa. The risk of preterm delivery in women with prior mid-trimester pregnancy loss approximates the same recurrence risk documented for women with a previous history of preterm delivery, suggesting that mid-trimester miscarriage represents the lower end of the spectrum of preterm birth. There are many causes of mid-trimester pregnancy loss including abnormal placentation, immunological interactions, thrombophilias, cervical insufficiency and upper genital tract anomalies to name a few. This paper, however, will focus on the role of chorioamnionitis in the pathogenesis of mid-trimester pregnancy loss and the value of current interventions to reduce recurrence.     

Mid-trimester severe intrauterine growth restriction is associated with a high prevalence of thrombophilia

Objective To investigate the association between severe mid-trimester IUGR, whose causes are unknown in most cases, and maternal thrombophilias.
Design Case–control study.
Setting Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, The Sackler Faculty of Medicine, Tel Aviv University.
Population Twenty-six women with severe mid-trimester (22–26 weeks of gestation) IUGR (birthweight  <3rd centile  ) and 52 matched multiparous women with normal pregnancies (controls).
Methods After excluding pregnancies with vascular maternal disease, chromosomal and structural aberrations and cytomegalovirus infection, 26 women out of 35 with severe mid-trimester IUGR remained and composed the study group. Each was matched for age, ethnicity and smoking status with two healthy women who had normal pregnancies. All the women were tested for genetic and acquired thrombophilias at least eight weeks after delivery.
Main outcome measures Prevalence of maternal thrombophilias.
Results The frequency of thrombophilias was 69% in the study group compared with 14% in the control group [odds ratio (OR) 4.5; 95% confidence interval (CI) 2.3–9, P  < 0.001  ]. The frequencies of factor V Leiden mutation, prothrombin gene mutation and protein S deficiency were significantly increased in the study group compared with the control group. The frequency of multiple thrombophilias was 33% in the study group versus none among the controls. Of the 26 pregnancies with severe mid-trimester IUGR, 13 ended in intrauterine fetal death before 25 weeks of gestation: 10 of these women had thrombophilia.
Conclusion Women with mid-trimester severe IUGR have an increased prevalence of inherited and acquired thrombophilias.     

Complications rate and pregnancy outcome in women who underwent early and mid trimester amniocentesis

OBJECTIVES: Evaluation of the complications rate, as well as pregnancy outcome, in women who underwent early and mid-trimester amniocentesis. MATERIAL AND METHODS: The study was conducted among 454 patients, including 162 women after the procedure performed before 15 gestational week and 292 patients who underwent classic amniocentesis. All patients were hospitalized in Division of Reproduction of University of Medical Sciences in Poznan between 1999 and 2005. The analysis, based both on clinical observations and questionnaire sent to patients, concerned especially the frequency of following complications: miscarriage, premature rupture of membranes and club foot in newborns. RESULTS: Total pregnancy loss rate due to amniocentesis amounted to 1.2% and 0.3% in early and mid-trimester amniocentesis, respectively, not reaching statistical significance. The frequency of club foot in newborns of mothers who underwent amniocentesis did not differ significantly between the groups, although it was four times higher in early amniocentesis group than in patients in whom mid-trimester amniocentesis had been performed. CONCLUSIONS: The safety of early amniocentesis is comparable with safety of mid-trimester amniocentesis.     

Subarachnoid cyst with hydrocephalus--a complication of mid-trimester amniocentesis

We report a child with a subarachnoid cyst with hydrocephalus following a mid-trimester amniocentesis. Although fetal trauma is a rare complication, it is important to stress the need to perform amniocentesis under ultrasound control. Children with neurological disease or convulsions of unknown origin in early infancy who are born to mothers who have had mid-trimester amniocentesis should have a CT scan as part of the investigations to exclude this rare but nevertheless important complication.     

Prediction of pre-eclampsia with maternal mid-trimester total renin, inhibin A, AFP and free beta-hCG levels

We wanted to study if maternal serum mid-trimester total renin, inhibin A, AFP or free beta-hCG levels predict the development of pre-eclampsia. Maternal serum alpha-fetoprotein (AFP) and human chorion gonadotrophin (beta-hCG) were evaluated in the screening programme for Down syndrome in 4356 patients prospectively. Data on pregnancy outcome were available in 1242 women. Pregnancy-induced hypertension (PIH) developed in 69 women, 282 women with uneventful pregnancy outcome were selected for controls. Serum total renin and inhibin A levels were measured retrospectively in the trisomy screening samples of 69 and 30 patients who later developed PIH, and in 282 and 7 patients, respectively, who had an uneventful pregnancy outcome. No significant differences were found in the levels of maternal mid-trimester serum total renin, inhibin A or free beta-hCG levels between PIH and healthy women. The multiples of the median (MoM) of AFP values were significantly higher in the subgroup of patients who later developed severe pre-eclampsia than in patients with mild pre-eclampsia or gestational hypertension and healthy pregnant women. Maternal mid-trimester serum levels of total renin, inhibin A and free beta-hCG are not predictive for development of PIH. High mid-trimester serum AFP values may help in the prediction of severe pre-eclampsia.     

Comparative audit of booking and mid-trimester ultrasound scans in the prenatal diagnosis of congenital anomalies.

During 1988 and 1989, 3565 women booked under consultants who performed an ultrasound scan at booking, whilst 4984 booked under consultants who performed a formal mid-trimester scan between 16 and 18 weeks. All significant anomalies diagnosed prenatally and in the neonatal period were recorded, the incidence in each group being 12.9/1000 and 9.83/1000, respectively (NS). The sensitivity of diagnosis before 20 weeks was 45 percent in the 'mid-trimester' group (kappa 0.62) compared with 30 percent in the 'booking' group (kappa 0.46), overall sensitivity of prenatal diagnosis, however, being similar in both groups (63 vs. 65 percent, kappa 0.77 vs. 0.79). Cardiac anomalies were the single largest group which were not detected equally prenatally in both groups. This study shows that formal mid-trimester scanning leads to anomalies being detected significantly earlier in the antenatal period. Although not statistically significant, three lethal anomalies were missed prenatally in the 'booking' group which we would have expected to diagnose on a mid-trimester scan. These figures are discussed in the light of previous reports.     

Effects of mid-trimester induced abortion on the subsequent pregnancy

The outcome of the pregnancy following (a) a mid-trimester termination of pregnancy (TOP) for fetal neural tube defect (NTD) (77 women = group 1); (b) mid-trimester TOP for fetal Down's syndrome (13 women = group 2); (c) delivery of a baby with NTD (119 women = group 3) was studied. The prenatal fetal loss was relatively high in all groups. In group 1 it was similar to that found in other studies after first trimester TOP, in group 2 it was associated with advanced maternal age and the unexpected finding in group 3 was not attributable to advanced maternal age. It is suggested that a previous NTD per se might increase the risk of fetal loss in the next pregnancy. A previous mid-trimester TOP for NTD was not associated with an increase in premature labour, small for dates babies or congenital abnormality in the next pregnancy, but there was a slight increase in the number of babies weighing less than 2500 g.     

Child outcome following mid-trimester amniocentesis: development, behaviour, and physical status at age 4 years

Summary. Four-year-old children whose mothers had mid-trimester amniocentesis ( n = 88) were compared with children whose mothers chose not to have the procedure ( n = 46). Intelligence, visual-motor-perccptual skills, language, behaviour, social competence, temperament, physical growth, hearing, and middle-ear function were measured using standardized procedures. Health histories were obtained by maternal report. The results suggest that the wide range of developmental and behavioural variables studied is not influcnced by removal of amniotic fluid in the mid-trimester. However, mothers who had amniocentesis were more likely to report a history of ear infections in their child ( P = 0.04). In support of this finding were the results of audiological assessment which demonstrated a trend toward a higher rate of bilateral middle-ear impedance abnormalities in children whose mothers had amniocentesis ( P = 0.06). Further study of the upper respiratory system is recommended to explore potential long-term sequelae of mid-trimester amniocentesis.     

Midtrimester pregnancy termination--contemporary methods and techniques. Review

The improvement in the diagnostic procedures for early detection of fetal abnormalities has led to an increase in the number of induced mid-trimester pregnancy terminations. Hence, the total number of pregnancies terminated in the second trimester comprises somewhere between 10 and 15% of all terminations, but they are responsible for 2/3 of the complications and half of the deaths. These simple facts draw our attention to the procedure. There are two main types of mid-trimester termination- surgical and medical. Surgical methods require special skills and qualification, while medical methods are considered safer and are more common. The latter group includes Oxytocin i.v., prostaglandin preparations Pg E2, Pg F2alpha, Pg E1 and their synthetic analogues, antiprogesteron drugs and etc. We have reviewed Bulgarian and foreign scientific resources and articles. We have outlined the recommendations of The Royal College of Obstetricians and Gynaecologists and William's Obstetrics. Also we have cited some relevant trials and we have made a short review of the available on the Bulgarian market prostaglandin preparations for mid-trimester pregnancy termination.     

Heat shock protein-containing exosomes in mid-trimester amniotic fluids

Exosomes are multivesicular bodies formed by inverse membrane budding into the lumen of an endocytic compartment. Fusion with the plasma membrane leads to their release into the external milieu. The incorporation of heat shock proteins into exosomes has been associated with immune regulatory activity. We have examined whether heat shock protein-containing exosomes are present in mid-trimester amniotic fluid. Exosomes were isolated from mid-trimester amniotic fluids by sequential low-speed and high-speed centrifugation followed by sucrose density gradient centrifugation. Biochemical characterization included floatation pattern in sucrose gradients, acetylcholinesterase (AChE) activity and Western blot analysis for exosome-containing proteins. Exosomes were present in each of 23 amniotic fluids tested. They banded at a density of 1.17g/ml in sucrose gradients, were positive for AChE activity and contained tubulin, the inducible 72kDa heat shock protein, Hsp72 and the constitutively expressed heat shock protein, Hsc73; they were negative for calnexin. Exosome concentrations correlated positively with the number of pregnancies. Heat shock protein-containing exosomes are constituents of mid-trimester amniotic fluids and may contribute to immune regulation within the amniotic cavity.     

An immature stillbirth with lymphangiectasis and gonadal agenesis.

To the best of our knowledge, this is the first reported case of gonadal agenesis in a mid-trimester abortion.     

The clinical significance of asymptomatic mid-trimester low placentation diagnosed by ultrasound

A prospective investigation of the problem of low placentation in mid-trimester, in uncomplicated pregnancies was performed. 773 pregnant women were included and 70 (9.1%) had a low-positioned placenta, defined as a placenta reaching or partially covering the cervical os, diagnosed by ultrasound between the 19th and 21st week of pregnancy. In no case did the placenta completely cover the cervical os. By repeat ultrasound examination in the 36th week of pregnancy, all low placentations had converted to normal position. Low placentation in mid-trimester was not associated with pregnancy complications or neonatal complications. A placenta reaching or partially covering the cervical os, in early pregnancy, seems to be normal, not influencing the subsequent course of pregnancy.     

Estimating the risk of a fetal autosomal trisomy at mid-trimester using maternal serum alpha-fetoprotein and age: a retrospective study of 142 pregnancies.

Risks appropriate for mid-trimester prenatal screening for autosomal trisomies have been estimated from a combination of maternal age and maternal serum (MS) alpha-fetoprotein (AFP) levels at 16-20 weeks gestation. Published data on the frequency of Down's syndrome births relative to maternal age were modified to include the additional age-related frequency of trisomy 18 and trisomy 13 cases to provide an overall risk for an autosomal trisomy at mid-trimester. MSAFP results from a retrospective study of 142 affected (114 trisomy 21, 19 trisomy 18, and 9 trisomy 13) and 113,000 unaffected pregnancies were converted to multiples of the appropriate gestational median (MOM). The AFP levels in the autosomal trisomy pregnancies were found to be significantly reduced at 0.72 MOM of the unaffected pregnancies. Risks (likelihood ratios) were derived from the overlapping log Gaussian distributions for affected and unaffected pregnancies and combined with maternal age risks to give the overall odds of an affected pregnancy. A mid-trimester cut-off risk of 1:280 gave an estimated 37 per cent detection rate for autosomal trisomies in the west of Scotland population for a follow-up (false-positive) rate of 6.6 per cent. These figures compare with a 30 per cent detection and 6.7 per cent false-positive rate if age 35 years and over is used as the sole criterion for selection of at-risk pregnancies.     

Down's syndrome screening in twin pregnancies by nuchal translucency measurement. Current concept

During the last 2 decades various non-invasive Down syndrome (DS) screening methods were introduced in clinical practice. However, specific problems were encountered when these methods were applied for twin pregnancies. The current review aims to explore the problematic issue of antenatal DS screening in twins. The implication and the adjusted management in the attempt to achieve the best evaluation for this type of gestation is discussed. Overall more women with twin pregnancies (mainly those who conceived via assisted reproduction) are found false positive for DS. This is because the standard screening algorithms include maternal age. In addition, mid-trimester maternal serum screening is associated with a higher false positive rate; secondary to changes in the feto-placental endocrinologic metabolism in assisted conception pregnancies. Therefore, in twins mid-trimester maternal serum screening is of limited clinical value. In those pregnancies, DS screening by means of nuchal translucency measurements at 10-14 weeks is associated with a lower false positive rate than mid-trimester serum screening. In addition, this screening method enables to specifically identify those fetuses at risk of DS and other anomalies, and thus contributes to a better outcome.     

Genetic amniocentesis: gestation-specific pregnancy outcome and comparison of outcome following early and traditional amniocentesis.

Amniocentesis remains the most common prenatal diagnostic invasive procedure for fetal karyotyping. During counselling prior to this procedure miscarriage rates are often quoted as a single figure. In this review of 2924 amniocenteses, we report that miscarriage rates vary with the gestational age at which the procedure is performed. The total miscarriage rate was 1.0 per cent after early amniocenteses (11 + 0-14 + 6 weeks) and 1.2 per cent after traditional mid-trimester amniocenteses (15 + 0-18 + 6 weeks). The rate was greatest (3.1 per cent) for amniocenteses performed after 18 + 6 weeks' gestation. The cumulative miscarriage risk increased from 0.03 per cent one week after the procedure to plateau at 1.1 per cent five weeks after the procedure. The preterm and still-birth rates following amniocenteses were similar in early and traditional mid-trimester amniocenteses but were significantly higher when amniocenteses were performed after 19 weeks' gestation. Although the incidence of talipes equinovarus was higher after early amniocentesis compared with traditional mid-trimester amniocenteses (1.4 per cent versus 0.2 per cent), none of the affected infants required corrective surgery. We conclude that counselling for this procedure should be tailored to each unit's unintended fetal loss rate based on cumulative rates. Such figures should be available to parents to assist them in their decision-making.     

Maternal serum alpha-fetoprotein (MSAFP) and fetal growth

Early mid-trimester screening of maternal serum alpha-fetoprotein (MSAFP) for the detection of neural tube defects is becoming a routine part of obstetrical care. In singleton pregnancies in the absence of fetal chromosomal abnormalities and anatomical anomalies high levels of AFP have been variably related to increased risk for low birthweight infant outcome. The overall relationship, if any, of maternal serum AFP to infant birthweight has, however, not been previously characterized. Between 15 and 20 weeks gestation, MSAFP values were determined for 110 women carrying single, anatomically and karyotypically normal fetuses. Statistical analysis utilizing polynomial and multilinear regression was used to determine the relationship of early mid-trimester MSAFP first to neonatal birthweight and then to gestational age and birthweight adjusted for gestational age. For every increase of one multiple of the median in MSAFP, neonatal birthweight fell 322 grams. This was accounted for almost entirely by decreased fetal growth; early mid-trimester MSAFP was linearly related to birthweight adjusted for gestational age ten times more strongly than to gestational age alone. The explanation for this relationship remains speculative, but the utility of routine AFP screening for the antenatal detection of intrauterine growth retardation certainly deserves further study.     

An elevated amniotic fluid matrix metalloproteinase-8 level at the time of mid-trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery.

OBJECTIVE: Strong evidence implicates chronic intra-amniotic inflammation in the etiology of mid-trimester abortion and spontaneous preterm delivery. The purpose of this study was to determine if concentrations of amniotic fluid matrix metalloproteinase-8, and cytokines such as interleukin-6 and angiogenin can identify patients at risk for spontaneous preterm delivery in patients undergoing mid-trimester amniocentesis. STUDY DESIGN: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin in patients who delivered at term and in those who delivered before term. The study included 19 cases with spontaneous preterm delivery and 95 matched controls with normal outcomes. Patients with abnormal fetal karyotypes or major anomalies were excluded. Matrix metalloproteinase-8, interleukin-6, and angiogenin were measured by using specific immunoassays. Mann-Whitney U tests, Fisher exact tests, and receiver-operating characteristic curves were used for statistical analysis. RESULTS: The median amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin concentrations of patients with spontaneous preterm delivery were significantly higher than those of control cases (matrix metalloproteinase-8: median, 3.1 ng/mL [range, 0.3-1954.9 ng/mL] vs median, 1.3 ng/mL [range, <0.3-45.2 ng/mL], P <.01; interleukin-6: median, 0.32 ng/mL [range, 0.04-2.52 ng/mL] vs median, 0.18 ng/mL [range, 0.01-1.81 ng/mL], P <.01; angiogenin: median, 11.1 ng/mL [range, 4.5-30.7 ng/mL] vs median, 6.7 ng/mL [range, 1.3-21.9 ng/mL], P <.001). Amniotic fluid matrix metalloproteinase-8 concentrations higher than 23 ng/mL had the highest specificity and odds ratio (sensitivity, 42% [8/19]; specificity, 99% [94/95]; OR, 68.4 [95% CI, 7.8-599.1]) in the identification of the patients with preterm delivery after genetic amniocentesis. CONCLUSIONS: Elevated mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin are a risk factor for early spontaneous preterm delivery (<32 weeks). An elevated matrix metalloproteinase-8 level of >23 ng/mL is a powerful predictor of spontaneous preterm delivery (<32 weeks) with an odds ratio of 68.4. Amniotic fluid studies can be used to improve the risk assessment for preterm delivery in women who undergo mid-trimester amniocentesis for genetic indications.     

Chorionic villus sampling and amniocentesis

PURPOSE OF REVIEW: The advantages and disadvantages of common invasive methods for prenatal diagnosis are presented in light of new investigations. RECENT FINDINGS: Several aspects of first-trimester chorionic villus sampling and mid-trimester amniocentesis remain controversial, especially fetal loss rate, feto-maternal complications, and the extension of both sampling methods to less traditional gestational ages (early amniocentesis, late chorionic villus sampling), all of which complicate genetic counseling. A recent randomized trial involving early amniocentesis and late chorionic villus sampling has confirmed previous studies, leading to the unquestionable conclusion that transabdominal chorionic villus sampling is safer. The old dispute over whether limb reduction defects are caused by chorionic villus sampling gains new vigor, with a paper suggesting that this technique has distinctive teratogenic effects. The large experience involving maternal and fetal complications following mid-trimester amniocentesis allows a better estimate of risk for comparison with chorionic villus sampling. SUMMARY: Transabdominal chorionic villus sampling, which appears to be the gold standard sampling method for genetic investigations between 10 and 15 completed weeks, permits rapid diagnosis in high-risk cases detected by first-trimester screening of aneuploidies. Sampling efficiency and karyotyping reliability are as high as in mid-trimester amniocentesis with fewer complications, provided the operator has the required training, skill and experience.