Spontaneous Fetal Loss Rate Research Articles

A Single Institutional Study on Pregnancy Outcomes in Patients with Von Willebrand Disease

Background:Von Willebrand Disease (VWD) is the most common inherited bleeding disorder in the United States. Despite von Willebrand factor (VWF) antigen and activity levels rising during pregnancy particularly in those with type 1 disease, there are several obstetric concerns regarding patients with VWD, including epidural management, mode of delivery, fetal outcome, and postpartum hemorrhage. Current guidelines suggest achieving a VWF activity (RCoF) and factor VIII:C level of at least 50 IU/dL before delivery, with maintenance > 50% of normal for at least 3-5 days.Aim:To investigate the incidence of obstetric complications in women with VWD and correlate maternal and fetal outcomes with VWF levels.Methods:We conducted a single-institution retrospective observational study reviewing the charts of all women diagnosed with VWD at the Hemophilia Treatment Center from January 2000 to June 2017. We included women with single or multiple pregnancies. We assessed the following obstetric outcomes: bleeding episodes during pregnancy, mode of delivery, use of epidural anesthesia, perioperative management of bleeding, prophylactic measures during peripartum period, presence of postpartum hemorrhage or excessive incisional bleeding, rate of spontaneous fetal loss, VWF/VIII:C levels during perioperative period, and transfusions. We excluded women with other diagnosed bleeding disorders. Statistical analyses were performed using the unpaired Student's t test.Results:The charts of 231 females with VWD were reviewed. There were 71 total pregnancies from 46 patients that were evaluable. 93.5% (43/46) patients had Type 1 VWD. 9.9% (7/71) had bleeding prior to delivery which included ecchymoses, mucosal or gingival bleeding, vaginal spotting, or epistaxis. Regional epidural anesthesia was performed in 16.9% (12/71) of cases with no bleeding complications reported. 25.4% had documented C-sections and 60.6% had vaginal deliveries. Postpartum bleeding (defined as immediate or delayed excessive vaginal or incisional bleeding) occurred in 29.6% (21/71) of cases; 38.9% (7/18) who underwent C-section and 25.6% (11/43) in vaginal deliveries. 50% (6/12) developed heavy bleeding despite receiving preoperative desmopressin (DDAVP) or human factor VIII/human VWF complex. 61.9% (13/21) required transfusions of blood products (either packed red blood cells or platelets), surgical dilation and curettage, IV/IN DDAVP or FVIII/VWF concentrates. 7% (5/71) had complications which included two ectopic pregnancies, two miscarriages, and one stillbirth, and one of these resulted in postpartum heavy bleeding (20%).The baseline and third trimester factor VIII:C and RCoF levels of non-bleeders and bleeders are shown in Table 1. The absolute difference in baseline levels of FVIII:C and RCoF compared to third trimester levels in non-bleeders was statistically significant: FVIII:C (p=0.0001; absolute difference of 53.6 IU/dL), RCoF (p=0.0001; absolute difference of 65.7 IU/dL), respectively. There was no statistically significant rise in FVIII:C nor RCoF levels from baseline to third trimester in women who had bleeding events (Table 1).Discussion:A reasonable estimate for the rate of postpartum hemorrhage in the general population is 1-5%. Our study demonstrated a much higher rate of postpartum bleeding in patients with VWD with a higher rate of hemorrhage in C-sections than vaginal deliveries. In those patients selected for epidural administration of regional anesthesia there were no complications. It appears that the rise in factor VIII:C and RCoF levels from baseline predicted the absence of bleeding and a larger absolute increase of VIII:C and RCoF from baseline levels predicted the absence of postpartum bleeding. In patients with postpartum bleeding, there was a smaller absolute increase in factor VIII:C and RCoF. In both groups, there were bleeding events despite prophylactic treatment prior to delivery.Conclusion:Our study suggests that greater increases of factor VIII:C and RCoF from baseline may predict the absence of postpartum hemorrhage in patients with VWD. Larger studies are needed to further elucidate the relationship between factor VIII:C and RCoF levels at baseline and peripartum and the risk of postpartum hemorrhage. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Total pregnancy loss after chorionic villus sampling and amniocentesis: a cohort study.

To identify maternal-, operator- and procedure-related variables that affect procedure-related pregnancy loss after transcervical (TC) and transabdominal (TA) chorionic villus sampling (CVS) and amniocentesis and to estimate the rates of spontaneous and procedure-related loss in comparable subgroups of women. This was a retrospective cohort study conducted at the University Medical Center Groningen and the Academic Medical Center, The Netherlands. Databases of both centers were searched to identify singleton pregnancies that had undergone a combined test and/or anomaly scan at around 20 weeks' gestation, or an invasive procedure (CVS and/or amniocentesis) between January 2001 and December 2011. Maternal characteristics, obstetric history, technical aspects of the invasive procedure, ultrasound examinations and fetal and neonatal outcomes were available for 29 201 cases. Women were categorized, according to the type of examination they had received, into the following five groups: first-trimester combined test (and 20-week anomaly scan); 20-week anomaly scan only; CVS; amniocentesis; amniocentesis after unsuccessful CVS. Rates of fetal loss were compared between groups. Variables significantly associated with a higher rate of fetal loss were, for CVS, repeat attempts during the procedure, use of TC cannula instead of biopsy forceps, gestational age at procedure ≥ 13 weeks and a pregnancy after assisted reproductive techniques, and, for amniocentesis, if indication was fetal anomaly or family history of anomalies and repeat attempts during the procedure. In women aged ≥ 36 years who did not undergo an invasive procedure, spontaneous fetal loss rate (FLR) after first-trimester combined test was 1.40%, whereas after CVS, FLR was 2.76% and 2.43% for a TC and TA approach, respectively. The additional risk of fetal loss with TC-CVS was therefore 1.36% (1 : 74), which varied according to the instrument used (0.27% for forceps and 3.12% for cannula), and with TA-CVS was 1.03% (1 : 97). In women aged ≥ 36 years who underwent a 20-week anomaly scan only, spontaneous FLR was 0.63%. In women who underwent amniocentesis solely because of advanced maternal age, FLR was 1.11%. The additional risk of fetal loss with amniocentesis was 0.48% (1 : 208). The total rate of procedure-related fetal loss after TA- and TC-CVS and amniocentesis appears lower than the risks on which women are currently counseled. There was a trend for a decrease in risk when the level of experience of the operator increased. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal screening for fetal aneuploidies during the first and second trimester of pregnancy

Prenatal screening for chromosomal defects during the first and second trimesters of pregnancy has become an established part of obstetric practice in many countries. The goal of current maternal serum screening programmes is to identify women who are at an increased risk of having a baby affected with Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) or neural tube defects and who will benefit from such diagnostic tests. The most commonly used test for genetic diagnosis is amniocentesis; however, the rate of spontaneous fetal loss caused by this test averages at about 1 in every 200 procedures. Because of this risk, serum analyte testing has become an important and non-invasive first step in detecting patients at risk of carrying a child with congenital abnormalities. The non-invasive screening options which are currently available to patients include combining maternal age with one of the following: first-trimester serum screening [nuchal translucency (NT) and maternal serum biochemistry markers]; second-trimester serum screening (maternal serum biochemistry markers such as the triple test and the quadruple test); or the two-step integrated screening, which comprises first- and second-trimester serum screening with or without NT.

Influence of chorionicity on perinatal outcome in a large cohort of Danish twin pregnancies

To assess outcome in twin pregnancies according to chorionicity. A cohort was retrieved from local ultrasound databases at 14 obstetric departments in Denmark, comprising all twin pregnancies with two live fetuses scanned between weeks 11 and 14 in the period 1 January 2004 to 31 December 2006. Outcome data were retrieved from the National Board of Health. Among 2038 twin pregnancies, 1757 (86.2%) were dichorionic (DC) and 281 (13.8%) were monochorionic diamniotic (MC). In MC pregnancies, the rate of spontaneous fetal loss in both second and third trimesters was more than threefold higher than the comparable rate in DC pregnancies: 6.0% vs. 1.9% for at least one fetus in the second trimester (P < 0.001) and 2.1% vs. 0.7% in the third trimester (P = 0.03). In 98.4% of DC pregnancies and in 91.1% of MC pregnancies, at least one infant was liveborn. Amongst pregnancies with two live fetuses at 24 weeks, the proportion with two live infants at 28 days after delivery was 97.5% and 95.1%, respectively. The increased incidence of fetal loss in MC pregnancies compared with DC pregnancies predominantly occurs before 24 weeks' gestation. After this stage, although the risk of intrauterine fetal death is still higher in MC than in DC pregnancies, if both fetuses are alive at 24 weeks, the chance of a woman having two live infants 1 month after delivery is similar in MC and DC pregnancies.

OC56: Miscarriage after a normal scan at 12–14 gestational weeks in women at low risk of carrying a fetus with chromosomal anomaly according to nuchal translucency screening

The aim was to estimate the risk of second-trimester miscarriage in women with a low risk of carrying a fetus with chromosomal abnormality according to nuchal translucency (NT) screening, and to determine if NT thickness or other factors affect the risk. The study population comprised 14 278 singleton pregnancies with a risk of Down syndrome < 1 : 250 at NT scan, and in whom no fetal karyotyping was performed at < 25 weeks. Risk factors for miscarriage were investigated by logistic regression. The median risk of Down syndrome was 1 : 3138 (range, 1 : 9651–1 : 251) and median NT was 1.7 (range, 0.4–3.0) mm. The miscarriage rate was 0.5% (77/14 278; 95% CI 0.4–0.6%). After controlling for maternal age we found the number of previous deliveries and miscarriages to independently predict miscarriage: odds ratio (OR) for each previous delivery 1.48 (95% CI, 1.22–1.80), P < 0.0001; OR for each previous miscarriage 1.34 (95% CI, 1.07–1.68), P = 0.01. Excluding women with any previous miscarriage and adjusting for parity we found a U-shaped relationship between maternal age and miscarriage (P = 0.04). In singleton pregnancies with an estimated risk of Down syndrome < 1 : 250 according to NT screening at 12–14 weeks, the spontaneous fetal loss rate before 25 weeks is likely to be around 0.5%. NT thickness up to 3 mm does not seem to affect the risk of miscarriage in such pregnancies. Instead, the risk seems to increase with number of previous miscarriages and deliveries, and possibly the risk is highest in the youngest and oldest women.

Miscarriage after a normal scan at 12–14 gestational weeks in women at low risk of carrying a fetus with chromosomal anomaly according to nuchal translucency screening

To estimate the risk of second-trimester miscarriage in women with low risk of carrying a fetus with chromosomal abnormality, according to nuchal translucency (NT) screening, and to determine whether NT thickness or other factors affect the risk. The study population comprised 14 278 singleton pregnancies with a risk of Down syndrome < 1:250 at NT scan, and where no fetal karyotyping was performed < 25 weeks. Risk factors for miscarriage were investigated by logistic regression. The median risk of Down syndrome was 1 : 3138 (range 1 : 9651-1 : 251) and median NT was 1.7 (range 0.4-3.0) mm. The miscarriage rate was 0.5% (77/14 278; 95% CI 0.4-0.6). After having controlled for maternal age, we found the number of previous deliveries and miscarriages to independently predict miscarriage: odds ratio (OR) for each previous delivery 1.48, 95% CI 1.22-1.94, P < 0.0001; OR for each previous miscarriage 1.34, 95% CI 1.07-1.68, P = 0.01. Excluding women with any previous miscarriage and adjusting for parity, we found a U-shaped relationship between maternal age and miscarriage (P = 0.04). In singleton pregnancies with estimated risk of Down syndrome < 1:250 according to NT screening at 12-14 weeks, the spontaneous fetal loss rate before 25 weeks is likely to be around 0.5%. NT thickness up to 3 mm does not seem to affect the risk of miscarriage in such pregnancies. Instead, the risk seems to increase with number of previous miscarriages and deliveries, and possibly the risk is highest in the youngest and oldest women.

Mid‐trimester amniocentesis and antibiotic prophylaxis

Assuming that the rate of fetal loss after amniocentesis may be reduced in patients receiving antibiotic prophylaxis, we conducted a retrospective study on untreated versus treated patients receiving prophylactic antibiotics (amoxicillin/clavulanic-acid or azithromycin) and evaluated the fetal loss rate within the 22nd week of gestation, also with respect to the risk of spontaneous abortion, both preexisting and related to mid-trimester amniocentesis. Spontaneous abortion occurred in 22 cases out of 1744 (1.26%). The incidence of spontaneous abortion was 1.3% among patients treated with antibiotic prophylaxis and 1.2% among untreated patients. Between patients with risk factors that predated amniocentesis, the spontaneous fetal loss rate was 9.2% in untreated patients versus 2.3% in patients treated (p = 0.10). In patients with procedure-related risk factors at amniocentesis, the spontaneous abortion rate was, respectively, 2.2 and 1.2% (p = 0.72). Our data demonstrate that antibiotic prophylaxis does not reduce the risk of spontaneous abortion within the 22nd week of gestation. Compared with untreated patients, patients treated with amoxicillin showed the lower fetal loss rate (1.16 vs 0.31%), but the difference was not statistically significant (odds ratio (OR) = 3.68, p = 0.32). The same was true for patients with preexisting risks (OR = 4.25, p = 0.10).

Pregnancy Loss Rates After Midtrimester Amniocentesis

The purpose of this study was to quantify the contemporary procedure-related loss rate after midtrimester amniocentesis using a database generated from patients who were recruited to the First And Second Trimester Evaluation of Risk for Aneuploidy trial. A total of 35,003 unselected patients from the general population with viable singleton pregnancies were enrolled in the First And Second Trimester Evaluation of Risk for Aneuploidy trial between 10 3/7 and 13 6/7 weeks gestation and followed up prospectively for complete pregnancy outcome information. Patients who either did (study group, n=3,096) or did not (control group, n=31,907) undergo midtrimester amniocentesis were identified from the database. The rate of fetal loss less than 24 weeks of gestation was compared between the two groups, and multiple logistic regression analysis was used to adjust for potential confounders. The spontaneous fetal loss rate less than 24 weeks of gestation in the study group was 1.0% and was not statistically different from the background 0.94% rate seen in the control group (P=.74, 95% confidence interval -0.26%, 0.49%). The procedure-related loss rate after amniocentesis was 0.06% (1.0% minus the background rate of 0.94%). Women undergoing amniocentesis were 1.1 times more likely to have a spontaneous loss (95% confidence interval 0.7-1.5). The procedure-related fetal loss rate after midtrimester amniocentesis performed on patients in a contemporary prospective clinical trial was 0.06%. There was no significant difference in loss rates between those undergoing amniocentesis and those not undergoing amniocentesis. II-2.

Age-specific risk of fetal loss observed in a second trimester serum screening population

The purpose of this study was to investigate age-specific spontaneous fetal loss rates of pregnancies without known chromosomal or structural abnormalities from mid-second trimester onward. The study consisted of 264,653 women screened between October 1995 and September 2000 with available pregnancy outcomes. Pregnancies associated with fetal chromosomal or structural abnormalities, insulin dependent diabetes mellitus, and multiple pregnancies were excluded. Spontaneous fetal losses at or after 15 weeks of gestation were identified. Women were grouped according to maternal age at expected date of delivery. Spontaneous fetal loss rates in each group were evaluated after adjusting fetal losses associated with amniocentesis and identifiable ethnic groups. Fetal loss rates increased in both younger and older women. The lowest rate was seen in women at mid-20s. Compared with Caucasian and Asian women, black women had higher fetal loss rate at nearly every age group. The results of the study provided a baseline age-specific spontaneous fetal loss rate of pregnancies at a specified gestational window.

The role of fetal nuchal translucency in prenatal screening.

An update of findings from studies on first trimester nuchal translucency screening. New first trimester markers can substantially improve efficacy of screening. When fully informed, preliminary data indicate that women prefer first trimester above second trimester testing. Recent reports on nuchal translucency screening reiterate the importance of standardization of technique and quality control as proposed by the Fetal Medicine Foundation in London. Effective quality control can be achieved through quantitative analysis of operator specific data. Three-dimensional ultrasound does not provide substantially higher success rates in obtaining reliable nuchal translucency measurements than two-dimensional ultrasound. New data confirm the previously reported association between increased nuchal translucency and increased rate of spontaneous fetal loss, genetic syndromes and a high prevalence (15%) of anomalies, among which cardiac defects are the commonest. Researchers agree that increased nuchal translucency ought to be an indication for specialized echocardiography. Promising data have become available on new markers that can enhance first trimester screening. It is estimated that when assessment of nasal bone and maternal serum analytes are taken into account, first trimester screening can identify 97.5% of trisomy 21 pregnancies for a 5% false-positive rate. It is stressed that parents need to be informed about the possible implications of screening before testing. Preliminary data indicate that when appropriately informed, women prefer first trimester above second trimester testing. Furthermore, the uptake of screening is likely to be relatively low among younger women.

Transcervical chorionic villus sampling in multiple pregnancies using a biopsy forceps

The aim of this study was to assess the effectiveness and safety of chorionic villus sampling (CVS) performed in multiple pregnancies by means of a transcervical biopsy forceps. The study included CVS performed from January 1990 to March 2000 in our Unit. The results were analysed in two consecutive periods, period A (1990-1994) and period B (1995-2000), in an attempt to assess the effect of increasing experience. Seventy-five samplings were performed in 39 multiple pregnancies, 38 twin sets and one triplet. A cytogenetic report was obtained in 73% of cases in period A and in 98% in period B. An abnormal karyotype was observed in 11 samples. The need for subsequent amniocentesis decreased from 38% in period A to 10% in period B. The spontaneous fetal loss rate in chromosomally and structurally normal fetuses before the 20th week decreased from 8.7% in period A to 3.3% in period B. The fetal loss rate after the 20th week was 3.3% in period B and none in period A. It must be noted that in three out of the four cases of fetal loss an amniocentesis was needed after CVS. Our results suggest that effectiveness and safety improved with increasing experience. Transcervical chorionic villus sampling allows an earlier prenatal genetic diagnosis in multiple pregnancies and this may be particularly relevant for a safer selective termination when chosen by parents if one of the fetuses has an abnormal karyotype.

Spontaneous fetal loss rates in a non‐selected population

The objective of this work was to determine the rate of spontaneous fetal loss up to 28 weeks of gestation in uncomplicated pregnancies of a low-risk population after sonographically identified intact intrauterine pregnancy during the first trimester. Transvaginal ultrasounds were given to 2,534 women at between six and 12 weeks of gestation. Inclusion criteria were a positive fetal cardiac activity and no antecedent signs of vaginal bleeding. Gestational age was confirmed by measurement of the crown-rump length and/or biparietal diameter (BIP). Patients were followed until delivery or up to a fetal loss. The mean fetal loss rate between 12 and 28 weeks was 3.86% (n = 99). Fetal loss increased with maternal age: fetal loss rate under 20 yr: 2.94% (OR 0.75; CI 0.23–2. 46), 20–24 yr: 3.20% (OR 0.77; CI 0.48–1.23), 25–29 yr: 3.39% (OR 0.77; CI 0.50–1.19), 30–34 yr: 3.89% (OR 1.01; CI 0.59–1.71), 35–39 yr: 7.82% (OR 2.13; CI 1.04–4.32), 40–45 y: 50% (OR 13.84; CI 6.67–28.72) and > 45 yr: 50% (OR 13.05; CI 1.96–86.71) respectively. The frequency of spontaneous fetal loss before 28 weeks gestation was assessed systematically in a low-risk population. There was a very clear correlation with advancing maternal age. These data now can be used as background loss rate information for evaluating the safety of invasive prenatal diagnosis, and they will be more valid for this purpose than the available data taken from selected cohorts of women, such as those from hospital clinics or from infertility programs. © 2001 Wiley-Liss, Inc.

Spontaneous fetal loss rates in a non-selected population

The objective of this work was to determine the rate of spontaneous fetal loss up to 28 weeks of gestation in uncomplicated pregnancies of a low-risk population after sonographically identified intact intrauterine pregnancy during the first trimester. Transvaginal ultrasounds were given to 2,534 women at between six and 12 weeks of gestation. Inclusion criteria were a positive fetal cardiac activity and no antecedent signs of vaginal bleeding. Gestational age was confirmed by measurement of the crown-rump length and/or biparietal diameter (BIP). Patients were followed until delivery or up to a fetal loss. The mean fetal loss rate between 12 and 28 weeks was 3.86% (n = 99). Fetal loss increased with maternal age: fetal loss rate under 20 yr: 2.94% (OR 0.75; CI 0.23-2. 46), 20-24 yr: 3.20% (OR 0.77; CI 0.48-1.23), 25-29 yr: 3.39% (OR 0.77; CI 0.50-1.19), 30-34 yr: 3.89% (OR 1.01; CI 0.59-1.71), 35-39 yr: 7.82% (OR 2.13; CI 1.04-4.32), 40-45 y: 50% (OR 13.84; CI 6.67-28.72) and > 45 yr: 50% (OR 13.05; CI 1.96-86.71) respectively. The frequency of spontaneous fetal loss before 28 weeks gestation was assessed systematically in a low-risk population. There was a very clear correlation with advancing maternal age. These data now can be used as background loss rate information for evaluating the safety of invasive prenatal diagnosis, and they will be more valid for this purpose than the available data taken from selected cohorts of women, such as those from hospital clinics or from infertility programs.

Fetal outcome and maternal morbidity after early amniocentesis

We have studied a large population-based cohort of women who had amniocentesis at 14 weeks' gestation (early amniocentesis) in Victoria, a state of Australia, to determine fetal loss rates and maternal morbidity. This was done by linking two registers--one containing information on all prenatal diagnostic tests in the state, and the other a register of all births at or after 20 weeks' gestation. Almost complete follow-up was achieved. The spontaneous fetal loss rate was significantly higher for women of age 37 years and over having early amniocentesis (2.5 per cent), as compared with the fetal loss rate found previously on the same geographically defined population who had amniocentesis at about 16 weeks' gestational age (1.1 per cent). Three classes of maternal morbidity reported to the birth register (post 20 weeks' gestation) were also analysed. The most significant finding was a reduced rate of premature rupture of membranes with early amniocentesis when compared with a group having later amniocentesis, or the background population not having any amniocentesis. There was no significant increase in the occurrence of antepartum bleeding or genito-urinary tract infection for women having early amniocentesis. These data agree with other studies in showing that early amniocentesis is associated with a significant increased risk of fetal loss, as compared with later amniocentesis. In addition we have shown no significant increase in the occurrence of three indicators of maternal morbidity, reported at or after 20 weeks' gestation.

Fetal outcome and maternal morbidity after early amniocentesis

We have studied a large population-based cohort of women who had amniocentesis at 14 weeks' gestation (early amniocentesis) in Victoria, a state of Australia, to determine fetal loss rates and maternal morbidity. This was done by linking two registers—one containing information on all prenatal diagnostic tests in the state, and the other a register of all births at or after 20 weeks' gestation. Almost complete follow-up was achieved. The spontaneous fetal loss rate was significantly higher for women of age 37 years and over having early amniocentesis (2·5 per cent), as compared with the fetal loss rate found previously on the same geographically defined population who had amniocentesis at about 16 weeks' gestational age (1·1 per cent). Three classes of maternal morbidity reported to the birth register (post 20 weeks' gestation) were also analysed. The most significant finding was a reduced rate of premature rupture of membranes with early amniocentesis when compared with a group having later amniocentesis, or the background population not having any amniocentesis. There was no significant increase in the occurrence of antepartum bleeding or genito-urinary tract infection for women having early amniocentesis. These data agree with other studies in showing that early amniocentesis is associated with a significant increased risk of fetal loss, as compared with later amniocentesis. In addition we have shown no significant increase in the occurrence of three indicators of maternal morbidity, reported at or after 20 weeks' gestation. © 1998 John Wiley & Sons, Ltd.

Transcervical chorionic villus sampling beyond 12 weeks of gestation

The aim of this study was to evaluate the feasibility of transcervical chorionic villus sampling (CVS) after 12 completed weeks of pregnancy. The transcervical route for CVS, using thin biopsy forceps, was accomplished in 335 procedures in the study group, between 12 + 1 and 15 + 0 weeks. Cases were subdivided into two subgroups, the late (13 + 0 to 15 + 0 weeks) and intermediate (12 + 1 and 12 + 6 weeks) subgroups, and the results were compared with a previous series of 1202 early (8 + 0-12 + 0 weeks) transcervical CVS. A successful diagnosis was made in 97.3% of the cases. No differences were found in diagnostic success between the study subgroups, in comparison to the early transcervical CVS series. However, success rates in the study group increased from 90% in the first 60 procedures to 98.9% in the remaining cases (p < 0.001). Amniocentesis was eventually performed in nine cases (2.7%). All cases were rescanned 2 weeks after the procedure, and fetal demise was detected in five cases (1.5%). The spontaneous fetal loss rate up to 28 weeks was 3.1% (2.7% for intermediate and 4.0% for late subgroups). No cases of transverse limb reduction defects were observed. The results of our study suggest that the transcervical route for CVS beyond the 12th week of pregnancy has a satisfactory diagnostic success rate, and an acceptable pregnancy loss rate.

Fetal cardiac anomalies

Fetal cardiac anomalies are increasingly identified during regular obstetric scanning. About 2 1000 pregnancies will have an abnormality of the four chamber view and a further 1 1000 will have an abnormality of the great arteries. These cases can then be referred to the specialist in fetal cardiology for further evaluation and counselling. There is a higher rate of chromosomal and other extracardiac anomalies in fetuses with congenital heart disease, so a careful study of the fetal anatomy, and often an amniocentesis, is indicated, particularly in continuing pregnancies. The natural history of many defects which are identifiable prenatally tends to be worse than that expected postnatally. This is because of an increased rate of spontaneous fetal loss, progression of cardiac disease prenatally and because a more severe spectrum of disease is seen in fetal life. Many parents will choose to interrupt a pregnancy where there is complex disease present. In continuing pregnancies, ideal management includes delivery of the affected infant in a center where postnatal treatment can be expedited immediately and cardiac surgery can take place if indicated.

Detection of pregnancies with trisomy 18 in screening programmes for Down's syndrome.

It is possible to identify pregnancies with trisomy 18 as part of screening programmes for Down's syndrome that use maternal age, IX fetoprotein (AFP), unconjugated oestriol (uE3), and either total human chorionic gonadotrophin (total hCG) or its subunit, free ~-hCG. While the detection rates and false positive rates using risk as the test variable have been published for maternal age with (a) AFP, uE3, and hCG 2 and with (b) AFP and free ~-hCG3 this has not been done for maternal age with AFP, uE3,and free ~-hCG. Here we summarise the parameters of the distributions of the markers in affected and unaffected pregnancies, and in affected pregnancies we calculate the' standard deviation for the free ~-hCG and the correlation between free i3-hCG and AFP and between free ~-hCG and uE3.We then estimate the detection rates and false positive rates. The parameters of the distribution of all four markers in unaffected pregnancies have been published. In trisomy 18 pregnancies: (a) the parameters for AFP, uE3, and total hCG were taken from reference 2; (b) the median free ~-hCG was taken from reference 3; (c) the standard deviation for free ~-hCG was calculated by taking the difference in variance between trisomy 18 and unaffected pregnancies from reference 3 and adding this to the unaffected variance from reference 4; (d) the correlation between AFP and free ~-hCG was calculated by taking the difference in covariance between trisomy 18 and unaffected pregnancies obtained from reference 3, adding this to the unaffected covariance from reference 4 and then dividing by the standard deviations in (a) and (c); (e) there is no available correlation between uE3 and free ~-hCG and so it is assumed to be the same as in unaffected pregnancies. The truncation limits (that is, the range over which the distributions are Gaussian) for AFP, uE3, and total hCG were taken from reference 2. The limits for free i3-hCG are not yet known and are therefore assumed to be the same as for total hCG because of the high correlation between these two markers. Table 1 shows the parameters for the serum markers in the detection of trisomy 18. As in Down's syndrome pregnancies, trisomy 18 pregnancies tend to have low values for AFP and uE3, but unlike Down's pregnancies they have low levels of total hCG and free ~-hCG. Table 2 shows the detection rates, false positive rates, and odds of being affected given a positive result (OAPR) when using maternal age (England and Wales, 1984-88), AFP, uE3, and either total hCG or free ~-hCG. The birth prevalence of trisomy 18 is taken as one tenth that of Down's syndrome' with a spontaneous fetal loss rate of 70% between 16 weeks and term. A mid-trimester risk cut off of 1 in 100 with AFP, uE3, and total hCG in combination with maternal age yields a detection rate of 59% and a false positive rate of 0·19%. The OAPR at term is 1:23. With a 1% fetal loss rate due to amniocentesis there would be 0·23 unaffected fetal losses for every term pregnancy

Chromosomal anomalies in fetal congenital heart disease.

A series of 467 cases of congenital heart disease detected in prenatal life were analyzed to identify the forms of cardiac malformation associated with karyotypic defects and to calculate the incidence of chromosomal abnormalities associated with such malformations. Of these, 77 were proved to have chromosomal anomalies although not all were karyotyped. The results were analyzed in two ways. First, the whole series of 77 cases was examined in order to describe the form of congenital heart disease found in association as, although many cases were forms of heart disease known to be associated with chromosomal defects, several were unexpected. In many cases which proved positive, there were other abnormal findings on ultrasound, further suggesting a high likelihood of a chromosomal defect. Some cardiac defects, however, such as atrial isomerism or transposition of the great arteries, were not associated with trisomies. The second part of the study examined in detail the records of 124 cases of congenital heart disease seen in 1989, as these were more completely documented than the previous cases. No chromosomal anomaly was therefore thought to be missed. Of this group, 20 (16%) proved positive. This is a higher rate than would be expected in an unselected population of live births. The difference between prenatal and postnatal life can be accounted for by the increased rate of spontaneous fetal loss in those with chromosomal defects. We conclude that, because of the high rate of chromosomal anomaly, all continuing pregnancies where congenital heart disease has been found in the fetus should be karyotyped unless specific types of heart defect which are rarely associated are confidently defined.

Allogeneic matings and immunization have different effects on nulliparous and multiparous mice.

CBA/J female mice have a high rate of spontaneous fetal loss when mated with DBA/2 males. We have confirmed that this fetal resorption rate can be significantly reduced by immunizing the female with C57BL rather than DBA leukocytes. The current studies have been extended to show the effect of continued immunization into second pregnancies. Three new findings emerge: second pregnancies in unimmunized CBA/J females X DBA/2 males proceed with a low percentage of spontaneous resorptions; continued immunization of multigravid, multiparous mice is associated with a high percentage of late onset fetal resorptions; and comparison of sex ratios between treated and untreated pregnancies showed no significant shift. These results suggest that untreated CBA/J females mated to DBA/2 males can be immunized to trophoblast antigens during first pregnancies, and that such immunization leads to "normal" reproductive outcome in subsequent untreated pregnancies. Persistent immunization with leukocytes appears to increase the percentage of fetal wastage in subsequent pregnancies regardless of whether the mother receives paternal or nonpaternal leukocytes. Intentional chronic immunization with male leukocytes does not influence the sex ratio of viable offspring. These data are discussed with reference to immunotherapy for women who suffer unexplained, recurrent spontaneous abortions.