Fetal Wastage Research Articles

Using genetic epidemiology to study Rett syndrome: the design of a case-control study.

Rett syndrome is a neurological disorder that is seen almost exclusively in females. Although generally considered to have a genetic basis, the underlying mechanism remains obscure. One favoured hypothesis is that the syndrome is an X-linked dominant disorder, lethal or non-expressed in males. Genealogical research has also suggested that the mode of transmission in Rett syndrome may involve a premutation which over several generations is converted to a full mutation. Geographical clustering has been reported, and it has also been proposed that Rett syndrome is a clinically variable condition and that other neurological disorders may be occurring more commonly in families with Rett syndrome. Other studies have found an apparent increase in intellectual disability and seizures in the extended families of girls with Rett syndrome. The science of genetic epidemiology can be used to identify familial aggregation, which is the clustering of a disorder within a family. We have used a case-control study design to investigate both fetal wastage and familial aggregation of other disorders in families of girls with Rett syndrome. The Australian Rett Syndrome Database provided the source of cases, and control probands were girls of a similar age with normal development. This paper describes the methodology for a case-control study of this rare condition using pedigree data and discusses issues in the collection and evaluation of such data. The use of a control population is an important feature. Both the strengths and the shortcomings of our design are identified, and recommendations are made for future research.

Autoimmunity and pregnancy loss.

Clinicians have recognized for several decades that certain autoimmune conditions, such as systemic lupus erythematosus (SLE), are associated with pregnancy loss. During the 1980s, investigations focused attention on fetal wastage in women with antiphospholipid antibodies and the antiphospholipid antibody syndrome (APS) was characterized. Its defining features include fetal wastage in the presence of significant levels of anticardiolipin antibodies. Since that time, interest in other autoimmune diatheses and various specific autoantibodies as possible causes of pregnancy loss has increased. Investigators have attempted to establish an association between recurrent pregnancy loss and the presence of a specific autoantibody or patterns of autoantibodies. Thus far, only modest evidence supports the concept that other autoantibodies are linked to, much less cause, pregnancy loss. In this review, we will define pregnancy loss in its various forms and discuss pregnancy loss in well-characterized autoimmune diseases such as SLE and APS. We will focus on the diagnosis and management of these conditions in women attempting to achieve successful pregnancies. Later we discuss the evidence concerning the less well defined association of antiphospholipid antibodies other than the lupus anticoagulant and anticardiolipin antibodies to recurrent pregnancy loss. We then outline the significance of antinuclear antibodies and antithyroid antibodies pertaining to adverse pregnancy outcome and conclude by summarizing and making some suggestions for further study.

Immonulogical background of recurrent fetal wastage

Immonulogical background of recurrent fetal wastage

Antiphospholipid antibody syndrome in renal transplantation: occurrence of clinical events in 96 consecutive patients with systemic lupus erythematosus.

We report the results of a detailed examination of clinical events associated with the antiphospholipid antibody (aPL) syndrome in 96 consecutive patients with systemic lupus erythematosus (SLE) who underwent renal transplantation between January 1, 1984, and September 1, 1996. Because of the retrospective nature of our study, we developed strict definitions of clinical events considered to be associated with the aPL syndrome. We reviewed all available hospital, clinic, and outside records of the patients with SLE who underwent transplantation at our center during this time period and noted the results of three standard serological tests for aPLs, when available. Mean follow-up of the 96 patients was 62.6 months. Eighty-five of the 96 patients (88.5%) had at least one test for aPLs performed, and 25 patients (29.4%) had at least one abnormal test result. Among these 25 patients, 15 patients (60%) had clinical events associated with aPL syndrome. Ten patients (10.4%) either died of the aPL syndrome or had an aPL-associated clinical event within 3 months of transplantation. Other morbidity from the aPL syndrome in these 15 patients included: thrombotic arteriolar microangiopathy (2 patients), stroke (4 patients), ocular ischemia (7 patients), deep vein thrombosis or pulmonary embolism (6 patients), renal artery or vein thrombosis (4 patients), peripheral ischemia (1 patient), and fetal wastage (3 patients). By comparison, among the 60 patients with normal aPL test results, only 5 patients had clinical events compatible with the aPL syndrome (P < 0.0001 by chi-squared test). aPLs may be associated with significant morbidity and mortality in patients with SLE undergoing renal transplantation. This study is the first attempt to quantify the impact of aPLs on renal transplantation in a large population of patients with SLE. Further investigation of aPLs in SLE patients with end-stage renal disease is required to clarify the risks, benefits, and optimal clinical management of renal transplantation for these patients.

Antiphospholipid-Thrombosis Syndromes

Antiphospholipid antibodies are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Based upon our experience, ∼25% of patients with unexplained venous thrombosis, ∼60% of patients with cerebrovascular thrombosis, ∼37% of patients with transient ischemic attacks, ∼18% with premature coronary artery thrombosis and ∼60% of patients with recurrent fetal loss (recurrent miscarriage syndrome) harbor antiphospholipid antibodies. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories have been advanced. Since the aPTT is unreliable in patients with lupus anticoagulant and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests, ELISA for IgG, IgA and IgM anticardiolipin antibodies and the dilute Russel’s viper venom time (followed by cephalin correction for confirmation) for lupus anticoagulant should be immediately ordered when suspecting the antiphospholipid syndrome in individuals with otherwise unexplained thrombotic or thromboembolic events or recurrent fetal loss. However, if one strongly suspects antiphospholipid thrombosis syndrome clinically and assays for lupus anticoagulants and anticardiolipin antibodies are negative, specific assays for all three idiotypes of phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol and phosphatidylglycerol are available and should be considered. These may clearly be indicated for difficult diagnostic cases of fetal wastage syndrome, and cerebrovascular events, but their significance in other types of thrombosis, particularly venous, remains unclear at present. Since about 65% of patients with antiphospholipid antibodies will fail warfarin therapy (rethrombose), it is important to define this common defect and institute appropriate antithrombotic therapy for appropriate time periods.

Patterns of pregnancy loss, perinatal mortality, and postneonatal childhood deaths in families of girls with Rett syndrome.

Rett syndrome is a neurodevelopmental disorder that occurs predominantly in girls and results in severe physical and intellectual handicap. A popular genetic mechanism is an X-linked dominant disorder, lethal in males. A case control study design was used to investigate fetal wastage as indicated by reported miscarriage and stillbirth prevalence, and the prevalence and cause of reported neonatal and other childhood deaths. There was no disturbance in the sibling sex ratio when case and control families were compared. In the parental generation and in the proband generation miscarriages were reported in similar proportions in case and control families. The reported stillbirth rates in case families was almost double that in control families and reported perinatal loss was more common on the maternal side in case families than in control families. Stillbirths and neonatal deaths affected slightly more boys in the parental and proband generations of case families (19 of 30) than in control families (10 of 21). Childhood deaths also occurred a little more commonly in Rett syndrome families. Sudden infant death syndrome was reported in three siblings of Rett syndrome probands but in no control siblings. Confirmation of this pattern of perinatal loss and infant mortality could indicate an alternative expression of the Rett syndrome gene.

Antiphospholipid syndrome and thrombosis.

Antiphospholipid antibodies [such as anticardiolipin antibodies (ACLA)] are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories have been advanced. The most common thrombotic events associated with ACLA are deep vein thrombosis and pulmonary embolus (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome) or cerebrovascular/retinal vessel thrombosis (type III syndrome), and occasionally patients present with mixtures (type IV syndrome). Type V patients are those with antiphospholipid antibodies and fetal wastage syndrome. It is as yet unclear how many seemingly normal individuals who may never develop manifestations of antiphospholipid syndrome (type VI) harbor asymptomatic antiphospholipid antibodies. The relative frequency of ACLA in association with arterial and venous thrombosis strongly suggests that these should be looked for in any individual with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed. Also, the type of syndrome (I through VI) should be defined, if possible, as this may dictate both type and duration of both immediate and long-term anticoagulant therapy. Unlike those with ACLA, patients with primary lupus anticoagulant thrombosis syndrome usually suffer venous thrombosis. Because the activated partial thromboplastin time (aPTT) is unreliable in patients with lupus anticoagulant (prolonged in only about 40 to 50% of patients) and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests including ELISA for ACLA, the dRVVT for lupus anticoagulant, hexagonal phospholipid neutralization procedure, and B-2-GP-I (IgG, IgA, and IgM) should be immediately ordered when suspecting antiphospholipid syndrome or in individuals with otherwise unexplained thrombotic or thromboembolic events. If these are negative, in the appropriate clinical setting, subgroups should also be assessed. Finally, most patients with antiphospholipid thrombosis syndrome will fail warfarin therapy and, except for retinal vascular thrombosis, most will fail antiplatelet therapy, thus it is of major importance to make this diagnosis in order that patients can be treated with the most effective therapy for secondary prevention, low-molecular weight heparin (LMWH) or unfractionated heparin (UHF) in most instances.

Interleukin-10 as an explanation for pregnancy-induced flare in systemic lupus erythematosus and remission in rheumatoid arthritis.

Rheumatoid arthritis (RA) and systemic lupus erythIL-10 production in human lymphocytes [6 ]. Increased ematosus (SLE) have in part overlapping clinical feaproduction of IL-10 may be of particular interest tures, but behave strikingly differently during pregnancy. because experimental work, in particular in Pregnant patients with SLE have a doubled incidence CBA×DBA/2 mice, showed that the administration of of flare [1], whereas diminution of disease activity IL-10 can prevent the elevated fetal wastage present in is observed in patients with RA [2]. Apparently, an this strain [7]. Moreover, administration of anti-IL-10 immunomodulating mechanism is activated during pregfurther increases fetal loss in this mouse model. Other nancy that is responsible for the opposite effect on the investigators recently identified a mechanism for active activity of these two autoimmune diseases. allo-immunosuppression in which IL-10 is of major Immunosuppression in pregnancy is essential to proimportance. tect the ‘allo-immune’ fetus. Already in the 1930s, the IL-10 was shown to drive the generation of antigensearch for the ‘pregnancy-induced’ immunosuppressive specific T cells that suppress antigen-specific immune factor ‘X’ had resulted in the discovery of glucocortiresponses [8]. These cells, designated Tr1 cells, could coids and subsequently Hench received the Nobel prize strongly reduce the alloantigen-specific proliferative for using corticosteroids to diminish disease activity in responses of autologous human CD4+ T-cell proliferaRA [3]. However increased secretion of corticosteroids tion. Activated Tr1 cells may create an environment in reduces disease activity in both SLE and RA, and which the allo-pregnancy is tolerated by active immunotherefore cannot explain the opposite effect of pregnancy suppression. The mechanism of this active immunosupon the activity of these diseases. Recently, it was reported pression was studied by determination of the cytokines that during pregnancy enhanced secretion of various produced by these Tr1 cells upon antigen-specific stimuimmunosuppressive cytokines, in particular translation. These cells secrete high levels of IL-10, but forming growth factor beta (TGF-b), interleukin (IL)-4 virtually no T-cell growth-promoting cytokines like IL-2 and IL-10 contributes to the state of tolerance in utero and IL-4. Thus, antigen-specific activation of Tr1 cells [4]. Here, the question is addressed whether pregnancyonly results in the production of immunosuppressive induced secretion of these cytokines explains both maincytokines and does not result in the production of tenance of an ‘allo’-pregnancy and the opposite influence essential growth factors for antigen-specific stimulation of pregnancy on disease activity in SLE and RA. of other T cells. Therefore, experimental data suggested that secretion of IL-10 to maintain pregnancy is importAllo-pregnancy and immunosuppressive ant to induce tolerance for the allo-immune fetus. The cytokines higher production of IL-10 in pregnancy has been demonstrated in an elegant study by Marzi et al. [9] Anti-inflammatory cytokines are produced at the materin which they showed that phytohaemagglutininnal–fetal interface in order to prevent feto-placental stimulated lymphocytes from mothers with a normal damage that could ensue from local inflammation [5]. pregnancy produced 85 pg IL-10/ml during the first Interestingly, the supernatants of fertilized human ovum trimester, 259 pg IL-10/ml during the second trimester harvested in in vitro fertilization procedures induced and 325 pg IL-10/ml during the third trimester, whereas lymphocytes from mothers with pregnancies that Submitted 26 August 1998; revised version accepted 25 January resulted in spontaneous abortions produced 15 pg 1999.

Multifetal pregnancy reduction: modification of the technique and analysis of the outcome

Objective: To modify the technique of multifetal pregnancy reduction and to study the outcome of reduced twins in comparison with nonreduced twins and high-order multiple gestations. Design: Prospective controlled study. Setting: The Egyptian IVF-ET Center, Cairo. Patient(s): Seventy-five patients with high-order multiple pregnancies resulting from assisted reproduction. Controls were 40 nonreduced twin pregnancies and 22 high-order multiple gestations. Intervention(s): Transvaginal ultrasonically guided multifetal pregnancy reduction was performed. The first 30 cases were done using KCl as a cardiotoxic agent. The modified technique was used for the last 45 cases at an earlier gestational age (approximately 7 weeks) by eliminating the use of KCl and by aspirating the embryonic parts. Main Outcome Measure(s): Miscarriage rate, gestational age at delivery, birth weight, and pregnancy complications. Result(s): Using the modified technique, the miscarriage rate was 8.8% and 41 patients delivered between 32 and 39 weeks of gestation (mean ± SD, 36.9 ± 2.45 weeks). The mean (± SD) birth weight was 2,450.51 ± 235.44 g. The miscarriage rate, fetal wastage rate, mean gestational age, and mean birth weight were similar in reduced and nonreduced twins and were significantly better than in nonreduced triplets and quadruplets. Conclusion(s): The modified technique of multifetal pregnancy reduction significantly improved outcomes, which were similar to those of nonreduced twins resulting from assisted reproduction and significantly better than those of nonreduced triplets and quadruplets.

Evaluation of the Different Antiphospholipid Antibodies for the Diagnosis of Antiphospholipid Syndrome

Objective: Antiphospholipid syndrome (APS) or Hughes syndrome is a frequently seen condition in Kuwait that is characterised by the presence of significant titres of a variety of antiphospholipid antibodies (aPL). The main clinical features of this syndrome include thrombosis (both venous and arterial), recurrent fetal wastage and thrombocytopenia. The aim of the present study was to find out the antibodies with a high predictive value for the diagnosis of APS. Methodology: The study included a total of 38 subjects. Nine of them were patients with proven primary APS, 10 with secondary APS and 19 were patients (controls) with weak clinical evidence of APS. After a complete clinical examination and routine investigations, the following categories of aPL were estimated by standard laboratory techniques: anticardiolipin antibodies of IgG and IgM isotypes (GPL and MPL, respectively), anti-β₂-glycoprotein-I antibodies (anti-β₂-GPI) of IgG and IgM isotypes and activated partial thromboplastin time as a surrogate for lupus anticoagulant (LAC). The tests were considered positive if the titres were more than a standard cut-off value provided by the manufacturer of the kits, and in one instance, the normal range was established in our laboratory (LAC). Results: The highest sensitivity (78.9%) and diagnostic accuracy (71.1%) were obtained by the estimation of GPL. However, excellent specificity (100%) and positive predictive value (100%) with almost as good a diagnostic accuracy (68.4%) were also obtained with anti-β₂-GPI of IgG isotype. All the other tests performed poorly when compared with these two. There was no difference in the performance of these tests between primary and secondary APS. Conclusion: Of the various aPL estimated, GPL and anti-β₂-GPI of IgG isotype were statistically sensitive and specific investigations for confirming the diagnosis of APS.

Structural chromosome rearrangements in couples with recurrent fetal wastage

Objective. A review of the cytogenetic data in 1743 couples (3486 patients) with recurrent fetal wastage (RFW) who were examined for RFW at the Leuven Centre for Human Genetics in the period 1986–1995. These results were compared with a previous study in the period 1970–1985. Subjects. Patients who had at least two first trimester miscarriages or patients who had a spontaneous first trimester abortion, preceded or followed by a second or third trimester fetal death. Results. Chromosomal rearrangements were found in 5.34%. Two-thirds of these chromosomal rearrangements were autosomal balanced translocations. This finding is a 30-fold increase compared to the general population. Other chromosomal abnormalities included Robertsonian translocations, inversions and sex-chromosomal abnormalities. Discussion. The Leuven experience was compared with several other studies. Mechanisms causing these chromosomal abnormalities are presented. Conclusions. Chromosomal analyses are an important and necessary part of the etiological investigations in couples with RFW.

Associations between Wife-Beating and Fetal and Infant Death: Impressions from a Survey in Rural India

This report examines the linkages between wife-beating and one health-related consequence for women, their experience of fetal and infant mortality. Community-based data are used drawn from women surveyed in two culturally distinct sites of rural India: Uttar Pradesh in the north, in which gender relations are highly stratified, and Tamil Nadu in the south, in which they are more egalitarian. Results suggest that wife-beating is deeply entrenched, that attitudes uniformly justify wife-beating, and that few women can escape an abusive marriage. They also suggest that the health consequences of domestic violence--in terms of pregnancy loss and infant mortality--are considerable and that Indian women's experience of infant and fetal mortality is powerfully conditioned by the strength of the patriarchal social system. Results are tentative because of data limitations, but they are consistent and strong enough to warrant concern. They argue for the integration of services to identify, refer, and prevent domestic violence in the primary or reproductive health programs of the country and for the safe motherhood programs to be particularly vigilant, sensitive, and responsive to the conditions of battered women during pregnancy and the postpartum period.

Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in mice.

Deficiency of blood coagulation factor V or tissue factor causes the death of mouse embryos by 10.5 days of gestation, suggesting that part of the blood coagulation system is necessary for development. This function is proposed to require either generation of the serine protease thrombin and cell signaling through protease-activated receptors or an activity of tissue factor that is distinct from blood clotting. We find that murine deficiency of prothrombin clotting factor 2 (Cf2) was associated with the death of approximately 50% of Cf2(-/-) embryos by embryonic day 10.5 (E10.5), and surviving embryos had characteristic defects in yolk sac vasculature. Most of the remaining Cf2(-/-) embryos died by E15.5, but those surviving to E18.5 appeared normal. The rare Cf2(-/-) neonates died of hemorrhage on the first postnatal day. These studies suggest that a part of the blood coagulation system is adapted to perform a developmental function. Other mouse models show that the absence of platelets or of fibrinogen does not cause fetal wastage. Therefore, the role of thrombin in development may be independent of its effects on blood coagulation and instead may involve signal transduction on cells other than platelets.

The "Unbooked Mother" at a University Teaching Hospital: Factors Mitigating Against Antenatal Clinic Attendance

Ever since the publication of Bellantyne in 1901, advocating a promaternity hospital, 1 the concept of prenatal care has grown progressively to become a universal component of obstetrics care, not only in the developed world, but also in the developing countries. Nevertheless, the problem of the “unbooked mother” presenting for delivery in the labor ward has continued to create a dilemma for many practicing obstetricians and other health care providers. This is because many obstetric units have to decide whether to admit the unbooked mother and accept all responsiblity for the possible complications and unfavorable outcome that may issue, or turn her away and bear the consequences for such drastic measures. The question that often arises is why the unbooked mother has not bothered to attend the antenatal clinic, 2 and how her non-attendance might affect the outcome of her pregnancy, especially in view of the high perinatal and fetal wastage among these mothers. 2-4 It may be possible that the unbooked mother requires little or no attention from the health care provider, because she receives no antenatal care and spends a relatively short time in hospital for delivery. 2,5 Indeed, some studies contend that there is no apparent difference between the booked and unbooked mothers in terms of obstetric outcome. However, it has been shown that the unbooked mother contributes very substantially to the perinatal morbidity and mortality of the average obstetrics unit, and constitutes a large drain on the resources of the Neonatal Intensive Care Unit (NICU). 9,10 If a mother does not book for care in the hospital, there is little that can be done to ensure a favorable outcome. Adverse reactions by the health care provider to the mother who has failed to book her pregnancy for care in the hospital, on the other hand, can only be counterproductive,

Antiphospholipid syndrome in pregnancy—animal models and clinical implications

The antiphospholipid (APS) syndrome frequently includes severe pregnancy complications such as fetal wastage and recurrent spontaneous abortions. Animal models for APS in pregnancy can provide both an understanding of the pathogenic mechanisms of anti-phospholipid antibodies (aPL), and aid in the evaluation of various therapeutic modalities in APS. Animal models for APS include both spontaneously developed diseases, as is the case for secondary APS in mice with another autoimmune disease, and induced models of APS. The latter includes either passive induction of disease by antibodies infusion, or active induction via manipulation of the idiotypic network. This article summarizes the literature reports of animal models of APS in pregnancy, deal with the various possible mechanisms of action of aPL in pregnancy, and discuss the treatment options of women having pregnancy complications of APS.

The Antiphospholipid Thrombosis Syndromes: A Common Multidisciplinary Medical Problem

Antiphospholipid antibodies are increasingly being identified as a cause of arterial and venous thrombosis as well as fetal wastage syndrome via placental vascular thrombosis. The antiphospholipid thrombosis syndromes should be considered and searched for when suggestive clinical findings are present or when unexplained arterial or venous thrombosis occurs. Noting the presence and type of antiphospholipid antibody thrombosis syndrome assumes major importance with respect to not only making an accurate diagnosis of cause of thrombosis but also in selecting effective antithrombotic therapy. The antiphospholipid thrombosis syndromes and the thrombotic and other clinical manifestations span almost all medical specialities and should be construed as a truly multidisciptinary medical problem. Key Words: Thrombosis-Anticardiolipin antibody—Lupus anticoagulant.

Quantitative analysis of constitutive heterochromatin in couples with fetal wastage.

Heteromorphism of constitutive heterochromatin is a stable evolutionary feature that is thought to cause no phenotypic alterations. Nevertheless, the role of constitutive heterochromatin is still unknown. The instability of constitutive heterochromatin was generally restricted to T-lymphocytes and was associated with variable immunodeficiency. The heterochromatin regions of chromosomes 1, 9, 16, and Y have been postulated to play a role in the immune response and during early embryo development. To investigate a possible influence of constitutive heterochromatin in human reproductive ability, quantitative analysis of constitutive heterochromatin in human chromosomes 1, 9, 16 and Y was done. Thirty couples were divided into two groups, owing to the clinical heterogeneity of their reproductive disorders. The first group included couples with two or more spontaneous abortions as the only pregnancy outcomes, and the second group included couples with a stillborn child with or without malformations. In the control group were couples with one or more healthy children without a history of fetal wastage. All of the persons in this study had normal karyotypes. The amount of constitutive heterochromatin was expressed by relative value using the simple transformation [q/(p + q)]. This value, obtained on GTG-banded metaphase chromosomes, represented an indirect measure of heterochromatin content. The Y/F index was used to express the relative amount of heterochromatin in chromosome Y. There was a significant increase in the heterochromatin content of the chromosomes 16 homologue pair in males and females with a stillborn or a stillborn malformed child (P < 0.01) and an increase in total heterochromatin cell content compared to controls (P = 0.005). The same couples had significantly increased mean maximal heterochromatin content in the potential zygotes (P < 0.02). The couples who experienced spontaneous abortions only had a minimal total heterochromatin content in the potential zygotes (P < 0.05). The Y/F index was significantly lower in the males in both groups compared to controls (P1 < 0.02; P2 < 0.02). The quantitative analysis of constitutive heterochromatin could be valuable in predicting pregnancy outcome.

Neonatal Deaths in the Asir Region of Saudi Arabia: Experience in a Referral Neonatal Intensive Care Unit

We reviewed a total of 169 deaths among 969 infants referred from various health institutions in the Asir Region to the neonatal intensive care unit of Asir Central Hospital, Abha, Saudi Arabia, during a four-year period (January 1992 to December 1995). The results showed that the major causes of neonatal mortality in the region were low birth weight (LBW) (45%), congenital malformations (CM) (30.8%), infection (13.6%), and birth asphyxia (7.7%). The majority of the LBW infants died from respiratory insufficiency, sepsis, and necrotizing enterocolitis. The alimentary, central nervous and cardiovascular systems were the parts most commonly involved in CM, with cardiac defect accounting for the highest fatality rate due to lack of facilities for cardiac surgery in the region, and delay in effecting a transfer. Klebsiella, Serratia and E. coli are the predominant organisms causing neonatal sepsis, in contrast with the group B streptococcus dominating in America and the United Kingdom. Generally, factors causing neonatal deaths in the Asir region are similar to those reported in other tertiary hospitals in Saudi Arabia, and tally closely with observations in America and Europe, where the standard of health care is excellent. Nevertheless, the study indicates the need for upgrading of facilities, as well as for more trained personnel for obstetric and neonatal care in Asir region. It may be necessary to consider the need for the establishment of a regional cardiac surgery center in the region.

Role of placental cytokines and inflammation in vertical transmission of HIV infection.

In light of new evidence suggesting that maternal human immunodeficiency virus (HIV) infection produces at least a three-fold increase in the number of early spontaneous abortions, it is important to search for factors that may predispose to fetal wastage. Immunological factors are thought to play an important role in permitting the HLA-disparate fetus to continue to term, despite powerful maternal immune forces capable of rejection. In the context of a heightened incidence of spontaneous abortion in HIV infection, evidence is now accumulating that implicates an imbalance in immune factors in contributing to this fetal loss. Soluble immune factors, such as cytokines, have been suggested as contributing agents to recurrent spontaneous abortions. Inflammatory cytokines-interleukin 1beta, interleukin 6 and tumor necrosis factor alpha-have been measured in isolated placental trophoblastic cells in HIV-infected and non-infected pregnant women in an attempt to explore this hypothesis. These inflammatory cytokines and their messenger RNAs were significantly elevated before and after stimulation in HIV-infected women, supporting the belief that HIV-infected women present their fetuses a milieu of imbalanced immune factors capable of contributing to immunological rejection. In addition, these elevated inflammatory cytokine levels may contribute to HIV disease progression in fetuses by virtue of activation of HIV gene transcription factors similar to what has been demonstrated in in vitro systems. We therefore propose that HIV infection in pregnant women produces an altered state of certain soluble immune factors, which in concert with other immune factor abnormalities, such as loss of immune selection in the fetal thymus, predisposes the fetus to advanced HIV infection and possible spontaneous abortion.

Effects of space flight on ovarian-hypophyseal function in postpartum rats.

The effect of space flight in a National Aeronautics and Space Administration (NASA) shuttle was studied in pregnant rats. Rats were launched on day 9 of gestation and recovered on day 20 of gestation. On day 20 of gestation, rats were unilaterally hysterectomized and subsequently allowed to go to term and deliver vaginally. There was no effect of space flight on pituitary and ovary mass postpartum. In addition, space flight did not alter healthy and atretic ovarian antral follicle populations, fetal wastage in utero, plasma concentrations of progesterone and luteinizing hormone (LH) or pituitary content of follicle stimulating hormone (FSH). Space flight significantly increased plasma concentrations of FSH and decreased pituitary content of LH at the postpartum sampling time. Collectively, these data show that space flight, initiated during the postimplantation period of pregnancy, and concluded before parturition, is compatible with maintenance of pregnancy and has minimal effects on postpartum hypophyseal parameters; however, none of the ovarian parameters examined was altered by space flight.