Biomedical subjects
Publications and source records attributed to L Lynch.
Information on congenital infection is continuously expanding. New diagnostic techniques are making significant contributions to the prenatal diagnosis of several fetal infections. In this review we highlight some of the most recent advances in the diagnosis and management of the most common fetal infections, those caused by cytomegalovirus, human immunodeficiency virus 1, Toxoplasma, varicella-zoster virus, and parvovirus B19.
Multifetal pregnancy reduction offers an acceptable option to patients faced with the significant risk of long-term morbidity associated with multifetal gestation, especially gestation involving 4 or more fetuses. Until advances in reproductive technology eliminate the iatrogenic occurrence of multifetal gestation, and until progress in perinatal care decreases the threat of preterm delivery, multifetal pregnancy reduction offers hope for a good outcome in an otherwise dismal situation.
OBJECTIVE: Our purpose was to determine the effect of first-trimester multifetal pregnancy reduction on maternal serum alpha-fetoprotein and coagulation profiles in the second trimester. METHODS: Maternal serum alpha-fetoprotein was determined in 57 patients 1.5 to 10 weeks after multifetal pregnancy reduction, and coagulation profile was determined in 17 patients 2 to 5 weeks after the procedure. All but one had living twins at the time of testing. RESULTS: All patients had elevated maternal serum alpha-fetoprotein levels (mean 11.6 +/- 7.6 multiples of the median) compared with normal twin values (< 3.5 multiples of the median). There was a positive correlation between maternal serum alpha-fetoprotein level and the number of dead fetuses and a negative correlation between maternal serum alpha-fetoprotein level and the number of weeks elapsed since multifetal pregnancy reduction. Amniotic fluid alpha-fetoprotein was measured in 10 patients and was normal. Fibrin split products were positive in 1 of 17 patients, intermediate in two of 17 and negative in 14 of 17. Prothrombin time, partial thromboplastin time, fibrinogen, and platelet counts remained normal. None of the patients had clinical evidence of disseminated intravascular coagulation, and treatment for that condition was not given. CONCLUSIONS: Maternal serum alpha-fetoprotein in the second trimester is always elevated after multifetal pregnancy reduction and is not necessarily indicative of fetal defects. This elevation is probably caused by release of tissue or serum from the dead fetus(es). Amniocentesis is not indicated in these cases, but ultrasonography to evaluate fetal anatomy should be considered because maternal serum alpha-fetoprotein cannot be used in these patients to screen for fetal defects. Some patients can have laboratory evidence of disseminated intravascular coagulation after multifetal pregnancy reduction, but it may resolve spontaneously.
OBJECTIVE: Pregnancy outcomes in patients with twin pregnancy undergoing second-trimester amniocentesis for fetal karyotype assessment were compared in a case-control study with twin pregnancies undergoing routine ultrasonographic studies at similar gestational ages. STUDY DESIGN: All spontaneous and induced twin gestations that underwent ultrasonographic examination between 14 and 20 weeks were compiled for the period January 1987 through January 1992. Patients having undergone multifetal reduction or chorionic villous sampling and those with fetal anatomic or chromosomal anomalies, discordant growth (> 20%), death, or a monoamniotic sac detected at ultrasonography were excluded. RESULTS: The mean (+/- SD) maternal age was significantly higher among the 101 cases than among the 108 controls (35.2 +/- 3.5 vs 30.4 +/- 5.3 years, respectively; p < 0.01). No differences were noted in gravidity, parity, number of prior spontaneous losses, or gestational age at ultrasonography between the two groups. The fetal loss rate was similar among cases and controls (seven of 202 [3.5%] vs seven of 216 [3.2%], relative risk 1.07, 95% confidence intervals 0.3 to 3.5). No losses occurred within 3 weeks of the procedure. Gestational age at delivery, birth weight, mean Apgar scores at 1 and 5 minutes, and length of neonatal stay were not significantly different between cases and controls. CONCLUSIONS: Second-trimester amniocentesis in twin pregnancies is apparently not associated with excess pregnancy loss.
OBJECTIVE: Multifetal pregnancy reduction has been proposed as a way to reduce the risk of preterm delivery in women who conceive three or more fetuses. This communication presents the outcome of 200 consecutive multifetal pregnancies in which reduction to a smaller number of fetuses was accomplished. STUDY DESIGN: All of the procedures were performed in the first trimester by the transabdominal injection of potassium chloride into the thoraces of those fetuses that underwent feticide. All of the pregnancies have been completed and outcome data have been obtained in every case. RESULTS: At the time of the procedure 88 women had triplets, 89 had quadruplets, 16 had quintuplets, and 7 had from 6 to 9 fetuses. These pregnancies were reduced to 189 sets of twins, 5 sets of triplets, and 6 singletons. Reductions to triplets were done at the patient's request, and reductions to singletons were only done for medical indications. There were no cases of chorioamnionitis or other maternal complications attributable to the procedure. A total of 181 women were delivered of one or more live infants after 24 weeks' gestation, and 19 (9.5%) lost all of their fetuses before that time. The mean gestational age for all women delivered after 24 weeks was 35.7 weeks. The mean gestational age at delivery varied inversely with the initial number of fetuses, from 36.1 weeks for women who presented with triplets to 33.8 weeks for those who had 6 or more fetuses, and this trend was statistically significant. Sixteen of the 19 complete pregnancy losses occurred > 4 weeks after the reduction procedure had been performed. The loss rates were 7.9% for those who presented with 3 or 4 fetuses, 12.5% for those with 5, and 42.9% for those with > or = 6. This trend was statistically significant. Two neonates died in the first week of life and one died at 10 months of age as a consequence of the sequelae of severe prematurity. Only two surviving infants have shown evidence of chronic morbidity related to early delivery, and all of the others are developing normally. CONCLUSION: The incidence of intrauterine growth retardation was not increased over that anticipated in a population of twins.
OBJECTIVE: Our investigation was designed to use maternal serum alpha-fetoprotein and individual or combinations of ultrasonographic parameters to examine the influence of fetal gender on the prediction of Down syndrome. STUDY DESIGN: A cohort study of 5114 patients who underwent karyotype analysis between 13 and 22 weeks' gestation was undertaken. Maternal demographic variables, anthropometric indices, and maternal serum alpha-fetoprotein values were assessed. Fetal parameters recorded included gender, biparietal diameter, head circumference, femoral and humeral length, transverse cerebellar diameter, and nuchal fold thickness. The effect of fetal gender on maternal serum alpha-fetoprotein values and ultrasonographic parameters was assessed. Gender-specific differences between fetuses with Down syndrome and euploid fetuses were identified, and the optimal cutoff values of individual and combinations of biometric parameters were determined by receiver operating characteristic curve analysis. RESULTS: A total of 42 fetuses with Down syndrome were identified. Female fetuses with Down syndrome had significantly lower maternal serum alpha-fetoprotein values than their male counterparts, and maternal serum alpha-fetoprotein screening paradigms resulted in the disproportionate identification of affected female fetuses. A nuchal fold thickness > or = 5 mm was the single best ultrasonographic predictor of Down syndrome independent of fetal gender. Affected male fetuses had significantly smaller mean femoral and humeral lengths than euploid fetuses after adjustment for biparietal diameter, but only the humeral length proved a clinically useful predictor of Down syndrome. Pearson's correlation coefficient confirmed that nuchal fold thickness and humeral length were independent of each other and of maternal age and maternal serum alpha-fetoprotein levels. The optimal ultrasonographic predictor of Down syndrome was the presence of either a nuchal fold thickness > or = 6 mm or a humeral length > 3.5 to 3.7 mm below the expected value. This combination of ultrasonographic findings identified 41.7% of female and 66.7% of male fetuses with Down syndrome. CONCLUSIONS: Fetal gender affects the prediction of Down syndrome by both maternal serum alpha-fetoprotein and ultrasonographic parameters. Moreover, the ultrasonographic detection of Down syndrome in fetuses is greatly improved by a combination of gender-specific biometric parameters.
Viruses like rubella, cytomegalovirus, varicella-zoster virus and parasites like Toxoplasma gondii can be transmitted from a pregnant woman to her fetus and can affect fetal development. Several factors determine the likelihood of fetal infection and the risk of consequences for the fetus, such as the timing of transmission during gestation or the immunologic status of the mother. No single diagnostic modality can be applied to all infections. Knowledge of the diagnostic methods available is essential for accurate counseling and treatment of affected pregnant women.
Information concerning the most recently discovered infections with perinatal implications is constantly expanding. Hepatitis C virus is responsible for the majority of cases of sporadic and transfusion-related non-A, non-B hepatitis. Its prevalence in the general obstetric population is approximately 2%, but it is much higher in intravenous drug users and recipients of blood transfusions. The risk of vertical transmission is probably small (approximately 4.5%), but mothers coinfected with hepatitis C virus and human immunodeficiency virus type 1 are at higher risk of transmitting infection, possibly as a result of higher levels of viremia. Parvovirus B19 infection can jeopardize the fetus in approximately 9% of cases, leading to profound anemia, followed by hydrops and death. B19 has not been proven to be teratogenic, but survivors have a greater risk of in utero growth retardation. Cytomegalovirus remains the most common cause of congenital infections, and the fetal effects of primary maternal infection during gestation can be devastating. Recurrent infections carry a much lower risk of vertical transmission. Prenatal diagnosis is feasible and reliable. The factors affecting the vertical transmission of human immunodeficiency virus type 1 have been further delineated, and new avenues of research have been opened.
OBJECTIVE: To evaluate the safety and efficacy of transabdominal multifetal pregnancy reduction (MFPR) in the management of iatrogenic and spontaneous multifetal pregnancies. METHODS: Data were combined from 463 completed pregnancies that underwent MFPR at major worldwide centers. RESULTS: Multifetal pregnancy reduction was performed with a 100% technical success rate (there were no failed procedures); 83.8% had delivery of potentially viable fetuses (defined as 24 weeks' gestation or later), and 83.5% of these viable pregnancies delivered at 33 weeks or later. The risk of fetal loss was 3.9% at 2 weeks or less post-procedure, 4.6% at 4 weeks or less, and 16.2% at less than 24 weeks of gestation. Gestational age at delivery varied principally with the number of fetuses remaining, with 7.1% delivering prematurely at less than 28 weeks, and 9.4% at 29-32 weeks. The incidence of obstetric and medical complications appeared to be unaffected, and there was no increase in congenital malformations. CONCLUSIONS: Multifetal pregnancy reduction is an efficient and safe way of improving outcome in multifetal pregnancies, unambiguously for quadruplets or more, and arguably for triplets. However, particularly at higher starting numbers, there are still suboptimal outcomes. We cannot answer the question of whether MFPR should be offered to women with triplets or twins. The only major risk appears to be fetal loss per se, and because the procedure itself does not damage the survivors, parental autonomy should be given a higher priority in the decision process than previously. However, to obviate the need for this procedure, infertility specialists must continue to be vigilant in the use of fertility drugs.
OBJECTIVE: The aim of our study was to determine whether the reported increased morbidity associated with failed attempted vaginal birth after cesarean section is attributable to the presence of a uterine scar alone or to labor preceding a cesarean section. STUDY DESIGN: Primiparous women (N = 237) who underwent repeat cesarean section after a failed trial of vaginal birth after cesarean section were retrospectively compared with 1582 nulliparous women who underwent a primary cesarean section after a failed trial of labor. RESULTS: There were no significant differences in maternal or neonatal morbidity between the two groups except for an increase in the prevalence of thin meconium in patients undergoing primary cesarean section. CONCLUSION: Our results suggest that the presence of a previous cesarean section scar does not increase the overall baseline morbidity associated with cesarean section after labor.
This study retrospectively reviewed 142 fatal cases of aortic laceration. Data were collected from the autopsy reports (including toxicology results) and included the circumstances of the injury. In the case of automobile crashes this included the direction of impact, time of day, and vehicular damage. Seventy percent of the victims were men with a mean age of 37.5 years; 30% were women with a mean age of 46 years. Thirty-five percent of the 142 victims had elevated blood alcohol levels. Fifty-four percent of the lacerations were located at the classic site (the isthmus). The majority of the aortic lacerations (102) were sustained in automobile crashes. Of these, 42% were broadside collisions and 58% were head-on collisions. Seventy-three percent and 67% of the victims in broadside and head-on collisions, respectively, had aortic lacerations at the classic site. The results suggest that the pathogenesis of aortic rupture involves a lateral oblique compression impact to the chest, which causes thoracic mediastinal structures to shift and deflect the aortic arch, resulting in severe shearing and stretching at the isthmus. The use of seat belts and air bags may reduce the number of aortic injuries.
OBJECTIVE: Neonatal alloimmune thrombocytopenia is caused by platelet antigen incompatibility between the mother and fetus. Affected fetuses may have severe thrombocytopenia leading to intracranial hemorrhage before or at birth. We sought to treat this condition in utero to prevent these hemorrhages. METHODS: Eighteen women who had previously delivered infants with severe alloimmune thrombocytopenia were treated with weekly infusions of intravenous gamma globulin from the diagnosis of fetal thrombocytopenia until birth; nine were also treated with corticosteroids. RESULTS: There were no intracranial hemorrhages in the treated fetuses, compared with ten cases among the 21 untreated siblings (48%). Only three treated fetuses, compared with 16 of 20 untreated siblings, had platelet counts of less than 30,000/microL, with no bleeding complications. CONCLUSION: Antenatal treatment of alloimmune thrombocytopenia with weekly gamma globulin effectively improves the fetal platelet count and prevents intracranial hemorrhage.
Many congenital infections can produce foetal diseases and are sometimes responsible for major disablements. The most frequent infectious foetal diseases are toxoplasmosis, rubella and chickenpox. Diseases caused by parvovirus or cytomegalovirus are exceptional. Foetal blood sampling has considerably simplified the prenatal diagnosis and made it accessible to more medical centres; it has also widened the therapeutic possibilities and above all, it has considerably reduced the number of therapeutic abortions. It may well be that the development of molecular biology, which has the great advantage of permitting an earlier diagnosis, will in the near future make it possible not only to detect numerous monogenic diseases before birth, but also to diagnose some foetal infections. We might then hope that a much earlier treatment in utero will also be more effective.
The usefulness of ultrasonography in detecting fetuses with Down syndrome in the second trimester has been the subject of considerable debate during the past 3 years. Conflicting reports have led to increasing confusion about the subject in the medical community and among the public. A review of the existing literature indicates that structural malformations that are chiefly cardiac are present in half of Down syndrome fetuses but are not consistently found during routine second-trimester ultrasonography. Although excess posterior nuchal skin-fold thickness is frequently present in infants with Down syndrome, it is also not consistently identified during second-trimester ultrasonographic examinations. Studies evaluating the efficacy of screening programs that are based on femur length shortening associated with Down syndrome have revealed markedly discrepant intercenter results. Although variations in methods may account for some of the observed variability, the magnitude of femoral shortening in Down syndrome suggests that this measurement may be only marginally useful. In summary, antenatal ultrasonography will allow for the detection of only those fetuses with Down syndrome who have multiple characteristic phenotypic features or anomalies. Moreover, current second-trimester ultrasonography does not appear to be either sensitive enough specific enough to be used as a unique Down syndrome screening modality; however, it may be a useful adjunct to maternal age and serum biochemical markers in the assignment of risk for Down syndrome.
Twelve fetuses were evaluated with a combination of ultrasonography, amniocentesis, and blood sampling for possible cytomegalovirus infection. In seven the mother had a documented primary cytomegalovirus infection. All seven women had normal ultrasonographic findings and one fetus was found to be infected. In the other five cases fetal cytomegalovirus infection was diagnosed in association with abnormal ultrasonographic findings. There was no history of maternal infection in the latter group. All positive and negative diagnoses were confirmed and none of the six infected fetuses survived. In this series, the most reliable parameters of infection were the isolation of the virus from amniotic fluid and elevations of total immunoglobulin M and gamma-glutamyl transpeptidase in fetal blood. In the majority of infected fetuses cytomegalovirus-specific immunoglobulin M was not detected in blood. Prenatal diagnosis of fetal cytomegalovirus infection is possible with a combination of amniocentesis and fetal blood sampling.
We have identified six new cases of Fanconi's anaemia (FA) who had pregnancies, and reviewed 11 others from the literature. At least 110 FA females have reached 16 years of age or more, of whom 15% became pregnant. There were a total of 26 pregnancies, resulting in 19 births and 18 surviving children. Anaemia and/or thrombocytopenia worsened during pregnancy in 10 patients, but five subsequently improved: seven had no haematological problems. Seven of the FA patients who had pregnancies died subsequently from cancer, and two from thrombocytopenic bleeding 3 and 20 years later. There were no peripartum deaths. Pregnancy in FA is clearly possible, with increased risks that are manageable from both the haematological and the obstetric aspects.
Congenital cytomegalovirus infection is the most common perinatal infection. We describe a case of primary maternal cytomegalovirus infection during pregnancy and the prenatal diagnosis of fetal cytomegalovirus infection. Diagnosis was accomplished with percutaneous umbilical blood sampling. The fetal blood was evaluated with viral cultures, cytomegalovirus serologic testing, and nonspecific indicators of infection. Amniotic fluid was also cultured. All cultures were positive, which confirmed fetal infection. The pregnancy was terminated. Autopsy findings were consistent with fetal infection. The significance and utility of prenatal diagnosis are discussed.
The role of high-dose intravenous (IV) gamma globulin in the treatment of erythroblastosis fetalis was assessed in five pregnancies with severe Rh (four) or Kell (one) isoimmunization. These women were treated with IV gamma globulin (1.0 g/kg body weight) once a week. In addition, fetal blood transfusions were performed when indicated. In four patients with Rh sensitization, high-dose IV gamma globulin treatment had no apparent effect on the total number of intrauterine transfusions required, the interval between transfusions, or the volume of blood required at each transfusion. The treatment did not prevent fetal hydrops and had no effect on maternal antibody titers. In one patient with Kell sensitization, however, the course of the disease was less severe than anticipated, suggesting that IV gamma globulin treatment may have modified the severity of the disease. We conclude that high-dose IV gamma globulin does not appear to be useful in the treatment of severe Rh disease. Its role in Kell and other types of red-cell isoimmunization deserves further evaluation.