Teratology最新文献

Background: Although previous studies provide some evidence that timing of prenatal care initiation is associated with risks of congenital malformation, the issue has not previously been examined in depth. This study uses data from a large population-based registry to explore the association of timing of prenatal care initiation with risks of selected congenital malformation phenotypes.

Methods: Data on cases were grouped according to four-digit malformation codes of the International Classification of Diseases, Ninth Revision (ICD-9). A randomly selected group of 10,000 nonmalformed deliveries served as the comparison group. Information on month of initiation of prenatal care (categorized as during months 1-3 of gestation, months 4-7, or after month 7) and other maternal characteristics were derived from vital statistics data.

Results: Among the 176 four-digit ICD groupings, 67 had an adjusted odds ratio for at least one of the two prenatal care categories that was either < or = 0.67 or > or = 1.50. Later prenatal care initiation was associated with risk > or = 1.50 for most groups. Later care was associated with risk < or = 0.67 for only two groups, and the effects were imprecise. Statistical interaction between parity and prenatal care was indicated for 13 groups (P < 0.10). Risks among women with no previous pregnancy tended to increase with later prenatal care initiation; risks among parous women tended to be somewhat weaker. In general, associations applied to a wide range of malformation groups.

Conclusions: This is the first large-scale study of the association of timing of prenatal care initiation and congenital malformation risks. Further defining the phenomena that surround prenatal care as a marker may help clarify the etiologies of a variety of malformations.

Background: The etiology of monozygotic twinning is not known. Some investigators have implicated abnormal X-inactivation, which could also be related to the increased female:male ratio in higher order multiple gestations in general, and in monozygotic and conjoined twins (CTS) in particular. CTS are rare, and even more unusual when part of a triplet pregnancy.

Methods: DNA polymorphism analysis using 13 markers in the buccal cells of the triplets and the lymphocytes of the parents were used to evaluate zygosity. We investigated the X-inactivation pattern of the triplets by analyzing methylation at the androgen receptor gene.

Results: We found a female triplet gestation consisting of CTS and a normal singleton. The thoracopagus CTS were joined from the clavicles to the umbilicus. Congenital heart disease was suspected antenatally, but the precise delineation of the heart defects required extensive postnatal evaluation. There was a single placental mass with a thin dividing membrane. Cesarean section was carried out at 32 weeks after the onset of labor. Histologically, the placenta was diamniotic monochorionic. The normal singleton did well after delivery; the CTS died at 35 days from cardiopulmonary collapse. The babies were monozygotic (>99.99% probability). Each baby in this triplet set exhibited a random and symmetric X-inactivation pattern. The degree of X-inactivation skewing fell in the range of 50-65%.

Conclusion: Genetic or environmental factors other than abnormal X-inactivation must be involved in causing monozygous multiple gestation or CTS. Despite prenatal diagnosis, shared myocardium or cardiac anomalies in CTS often determine the prognosis.

Background: Caspases play a pivotal role in the regulation and execution of apoptosis, an essential process during limb development. Caspase 8 activation is usually downstream of the Fas/FasL death receptors, whereas caspase 9 mediates the mitochondrial signaling pathway of apoptosis. Caspase 3 is an effector caspase. Previous studies have shown that the exposure of embryonic murine limbs in vitro to 4-hydroperoxycyclophosphamide (4-OOHCPA), an activated analog of the anticancer alkylating agent, cyclophosphamide, induced limb malformations and apoptosis. The goal of this study was to determine the role of caspases in mediating apoptosis in this model system.

Methods: Limb buds from gestational day 12 CD-1 mice were excised and cultured in roller bottles in a chemically defined medium for up to 6 days in the absence or presence of 4-OOHCPA. Apoptosis was indicated by internucleosomal DNA fragmentation, as detected by TUNEL staining. The profile of caspase activation was characterized by Western blot analysis and immunohistochemistry of control and treated limbs. To determine the consequences to limb morphology of inhibiting caspase activation, DEVD-CHO, a caspase-3 inhibitor, was added to the cultures.

Results: Limbs cultured in the presence of 4-OOHCPA were growth retarded and malformed; apoptosis was increased in the apical ectodermal ridge and interdigital areas. Western blot analysis showed that 4-OOHCPA exposure did not activate procaspases 8 or 9 in limbs. In contrast, procaspase-3 cleavage was increased in a concentration and time-dependent manner after exposure of limbs to 4-OOHCPA. Immunoreactive activated caspase-3 was localized in the interdigital areas and the apical ectodermal ridge region in control limbs; staining in these areas and in the interdigital areas was increased dramatically in limbs exposed to 4-OOHCPA. Inhibition of caspase 3 activation with DEVD-CHO partially protected limbs from insult with 4-OOHCPA.

Conclusion: Caspase-dependent and caspase-independent pathways of cell death are both important is mediating the abnormal limb development triggered by insult with 4-OOHCPA.

Background: Systemic lupus erythematosus (SLE) with or without evidence of antiphospholipid antibodies (aPA) and antiphospholipid syndrome (APS) is associated with a high rate of spontaneous abortions. The placenta is thought to be the site of pathological damage in many of these abortions. To test this hypothesis, we studied the effects of sera obtained from women with SLE with or without treatment on human placental explants in culture.

Methods: We cultured 5.5- to 7.5-week-old human placental explants in a culture medium containing F-12 DMEM and 10% FCS or in 90% human serum obtained from nonpregnant women with SLE prior to or after treatment. Culture was carried out for 96 hr. At the end of the culture period, we studied the secretion of the placental hormones estrogen (E2), progesterone (PGN), and human chorionic gonadotropin (hCG). In addition, we studied the proliferation rate (using PCNA staining) and the rate of apoptosis (using ApoTag) of the trophoblastic cells.

Results: Placentae grew better in normal human serum than in a chemically defined medium of F-12 DMEM and 10% FCS. Enhanced growth and higher secretion rates for hCG and estradiol (E2) were manifested in placentae cultured in control sera with no change in PGN secretion. Secretion rates of hCG and PGN (but not of E2 in the treated group) by placental explants were similar to that of controls. However, the serum levels prior to culture were not measured. Further, explants in serum from untreated women with SLE produced a significant decrease in the proliferation rate of the trophoblastic cells and an increase of apoptosis. Treatment significantly reduced the apoptotic rate and increased cell proliferation, but the cell proliferation rate was still lower than that noted in controls.

Conclusions: We conclude that sera from women with SLE may directly damage the developing placenta reducing proliferation and enhancing apoptosis. Successful treatment of the women reduces that damage.

Background: We present a case of partial facial duplication in a male infant.

Methods: The clinical, radiological, and laboratory findings for this patient are described, followed by a review of the literature.

Results: Craniofacial duplication is a rare form of conjoined twinning and presents in a wide spectrum, from dicephalus to diprosopus to partial facial duplication. Many of these cases can be diagnosed prenatally. Prenatal assessment of our patient revealed only agenesis of the corpus callosum.

Conclusions: The pathogenesis is believed to involve duplication of the notochord. Where there are more severe associated anomalies, the prognosis is poor. Partial facial duplication, as in our case, is associated with fewer anomalies, and the prognosis is better. Symmetry and an excess of tissue, rather than deficiency, favor a positive result.