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Cocaine abuse during pregnancy: Correlation between prenatal care and perinatal outcome
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ovarian hyperstimulation. The use of a gonadotropin releasinghormone agonist (GnRH-a) with hMG induction of ovulation may improve the therapeutic outcome. In this prospective, randomized trial, 27 women with PCOS underwent a total of 25 cycles of hMG alone and 33 cycles with adjunctive GnRH-a (leuprolide) treatment. Premature luteinization was seen less frequently in the leuprolide-treated cycles than in cycles treated with hMG alone. There were no differences between the treatments in ovarian sensitivity to hMG. Cycle fecundity was 0.16 for hMG alone cycles, and 0.27 for leuprolide with hMG cycles, which were not statistically different. We conclude that the sensitivity of the PCOS ovary to hMG is not affected by 4 weeks of leuprolide pretreatment. Longitudinal ultrasonographic study of the ovarian suppressive activity of a low-dose triphasic oral contraceptive during correct and incorrect pill intake Hami1tonC.J.C.M.; Hoogland H.J. Department of Obstetrics and Gynecology, Academic Hospital, P.O. Box 1918, 6201 BXMaastricht, NLD AM. J. OBSTET. GYNECOL. 1989, 16115 (1159-1162) A longitudinal study was conducted to evaluate the ability of a low-dose triphasic oral contraceptive to suppress ovulation as documented by frequent ultrasonographic scanning and progesterone determinations, even in the event of a missed pill. The extent of follicular growth and maturation, the incidence of escape ovulation, and the effect of correct and incorrect pill intake were assessed in 30 evaluable women during two consecutive spontaneous menstrual cycles. After the first cycle, 11 of 30 women (36.6%) had follicle-like structures of at least 10 mm in diameter. Ten of 11 structures gradually disappeared during the second cycle, with one persistent structure remaining through the second cycle. Seven of 30 women (23%) developed follicle-like structures during the second cycle. Of these, one woman had a probable ovulation, and another had an elevated progesterone level without follicle rupture, suggesting the luteinized unruptured follicle syndrome. Both of these women missed a pill on day 1 of the second cycle. In all cases cervical scores indicating hostility were noted. Thus, although suppression of ovarian activity may have been incomplete when oral contraceptives were incorrectly taken, secondary mechanisms of contraception remained operant. Low-dose triphasic oral contraception consistently prevented ovulation. Estrogerdc action of tamoxifen in women treated with luteinizing hormone-releasing hormone agonists (goserelin). Lack of shrinkage of uterine fibroids Lumsden M.A.; West C.P.; Hillier H.; Baird D.T. Department of Obstetrics and Gynaecology, University of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9E W, GBR FERTIL. STERIL. 1989,52/6 (924-929) Six premenopausal women with uterine fibroids were treated with a combination of tamoxifen, 20 mg/d, and goserelin, 3.6 mg every 28 days, for a total of 24 weeks. Results were compared with those from six women, matched for pretreatment uterine volume, who had been treated with goserelin alone. Int J Gynecol Obstet 32
During combined therapy, plasma and urinary estrogen concentrations were significantly lower than during goserelin alone, whereas sex hormone binding globulin concentrations were significantly higher. Plasma luteinizing hormone and follicle stimulating hormone (FSH) concentrations were both suppressed, in contrast with results during goserelin alone when FSH levels remained within the pretreatment range. None of the women on combined therapy bled in response to the endocrine changes of the initial treatment cycle. Despite this profound pituitary-ovarian suppression, there was no significant change in uterine volume during combined therapy. These results suggest that tamoxifen is acting as an estrogen agonist in women rendered hypoestrogenic with luteinizing hormone-releasing hormone agonists. Nocturnal melatonin levels are unaltered by ovarian suppression in girls with central precocious puberty Berga S.L.; Jones K.L.; Kaufmann S.; Yen S.S.C. University of California, San Diego School of Medicine (T002), San Diego, CA, USA FERTIL. STERIL. 1989,52/6 (936-941) Girls with central precocious puberty were utilized as a model in which to study the melatonin secretory response to ovarian suppression. Eight girls with central precocious puberty documented by clinical and endocrine characteristics, including sleep-entrained augmentation of luteinizing hormone (LH) pulsatility, were investigated. Nocturnal (6:00 P.M. to 9.00 A.M.) plasma melatonin levels were measured hourly by a sensitive and specific radioimmunoassay before and after gonadotropin-ovarian downregulation with gonadotropinreleasing hormone (GnRH)-agonist. Although nocturnal melatonin elevations varied widely between girls, patterns within the same individual were remarkably reproducible and unaltered before and after treatment. Although estrogens have been shown to modulate melatonin synthesis and secretion, in this model, reduction of estrogen levels was not associated with alterations in plasma melatonin concentrations.
PREGNANCY, DELIVERY Cocaine abuse during pregnancy: Correlation between prenatal care and perinatal outcome MacGregor S.N.; KeithL.G.; Bachicha J.A.; Chasnoff I.J. Department of Obstetrics and Gynecology, Northwestern University Medical School, Chicago, IL, USA OBSTET. GYNECOL. 1989,74/6 (882-885) Cocaine abuse during pregnancy has been associated with increased perinatal morbidity and mortality regardless of the quantity or quality of prenatal care. In this study, we tested the hypothesis that among cocaine-abusing women delivering at the same institution, those receiving comprehensive prenatal care have better perinatal outcome than those receiving little or no prenatal care. Between January 1, 1984 and July 1, 1987, 120 pregnant women who abused cocaine received multidisciplinary prenatal care in the Perinatal Center for Chemical Dependence of Northwestern University (group 1). During this
Citations from the Literature same period, we identified 21 cocaine-abusing parturients at our institution who were not enrolled in the Perinatal Center for Chemical Dependence and who received little or no prenatal care (group 2). Control subjects were selected from the general obstetric population for comparison. Data from these two groups were compared with each other and with matched control pregnancies. Group 2 pregnancies had lower mean gestational age at delivery, lower mean birth weight, and a higher incidence of preterm delivery than group 1 pregnancies. Furthermore, groups 1 and 2 were significantly different from control pregnancies for these parameters. We conclude that comprehensive prenatal care may improve outcome in pregnancies complicated by cocaine abuse; however, the perinatal morbidity associated with cocaine abuse cannot be eliminated solely by improved prenatal care. Bias against the null hypothests: The reproductive hazards of cocaine Koren G.; Shear H.; Graham K.; Einarson T. Motherbk Programme, Department of Pediatrics, Divkion of CIinical Pharmacology, Hospitai for Sick Children, 555 University Avenue, Toronto, M5G IX8 Ont., CAN LANCET 1989,2/8677 (1440-1442) To examine whether studies showing no adverse effects of cocaine in pregnancy have a different likelihood of being accepted for presentation by a large scientific meeting, all abstracts submitted to the Society of Pediatric Research between 1980 and 1989 were analysed. There were 58 abstracts on fetal outcome after gestational exposure to cocaine. Of the 9 negative abstracts (showing no adverse effect) only 1 (llolo) was accepted, whereas 28 of the 49 positive abstracts were accepted (57%). This difference was significant. Negative studies tended to verify cocaine use more often and to have more cocaine and control cases. Of the 8 rejected negative studies and the 21 rejected positive studies, significantly more negative studies verified cocaine use, and predominantly reported cocaine use rather than use of other drugs. This bias against the null hypothesis may lead to distorted estimation of the teratogenie risk of cocaine and thus cause women to terminate their pregnancy unjustifiably Maternal
phenylketonuria and hyperphenylalaninemia: for medical practice in the United States Luder AS.; Green C.L. Inherited Metabolic Diseases Clinic, University of Colorado Health Sciences Center, Box CZ33, 4200 E. 9th Ave., Denver, CO 80262, USA AM. J. OBSTET. GYNECOL. 1989, 161/5 (1102-1105) The risk of maternal phenylketonuria and hyperphenylalaninemia syndrome, a preventable cause of severe birth defects and retardation with a near 100% recurrence risk if untreated, is increasing in the United States. The reasons for this are reviewed. Women with hyperphenylalaninemia and those with phenylketonuria diagnosed and treated at birth are intellectually normal, as are some women with undiagnosed phenylketonuria. Both groups are at risk for maternal phenylketonuria syndrome in their offspring if blood Implications
297
phenylalanine levels are not controlled by diet during pregnancy. The problems and pitfalls of suspecting, diagnosing, and managing the condition are discussed. Suggested strategies for reversing the increasing trend include the greater use of genetic registers, increased clinical awareness, and some form of rescreening. The advantages and costs of rescreening a subset of pregnant women or all pregnant women at or before their first registration are examined. Amniotic fhdd particles: Are they related to a mature amniotic flnid phospholipid profile? Helewa M.; Manning F.; Harman C. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Manitoba, Winnipeg, Man., CAN OBSTET. GYNECOL. 1989,74/6 (893-896) In a prospective, blinded clinical study, the relationship between amniotic fltid free-floating particles measured by a dynamic ultrasound imaging method and phospholipid profile was studied in 82 women undergoing amniocentesis between 26 -42 weeks’ gestation. None of 11 patients with sonographitally clear amniotic fluid had a mature phospholipid profile (lecithin-sphingomyelin ratio greater than 2 and detectable phosphatidylglycerol). Thirty-eight of 71 women (53W) with turbid or markedly turbid amniotic fluid had a mature phospholipid profile. The sensitivity of this method was lOO%, specificity 25%, positive predictive value 53%, and negative predictive value 1OOolo.Although the Ending of sonographitally clear amniotic fluid may eliminate unnecessary amniocentesis, markedly turbid amniotic fluid is not a reliable indicator or a mature amniotic fluid phospholipid profile. Examination of amniotic fluid in diagnosing congenital syphilis with fetal death Wendel G.D.; Maberry M.C.; Christmas J.T.; Goldberg M.S.; Norgard M.V. Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dollas, TX 75235, USA OBSTET. GYNECOL. 1989,74/6 (967-970) The diagnosis of congenital syphilis is difficult, particularly in stillborn fetuses, who are often macerated and have undergone autolysis. These changes can obscure both syphilitic histology findings and special stains for spirochetes in tissue specimens used to confirm the diagnosis of congenital syphilis. Five gravidas with untreated syphilis and fetal deaths underwent sonographic examination and amniocentesis. In all five cases, dark-field microscopic examination of the amniotic fluid showed spirochetes with morphology and motility characteristics of Treponema pallidum. Organisms were infrequent, but easily identified at 400 x magnification and confirmed using an oil-immersion objective yielding a 900 x magnification. After delivery, fetal-placental examination and autopsy showed clinical findings typical of congenital syphilis in all five cases. Histologic changes compatible with syphilis were found in all four autopsied fetuses. Silver impregnation stains were positive in two of five tissue specimens, and anti-treponemalmonoclonal antibody immunofluorescence assays were positive Int J Gynecol Obstet 32
Citations from the Literature
ovarian hyperstimulation. The use of a gonadotropin releasinghormone agonist (GnRH-a) with hMG induction of ovulation may improve the therapeutic outcome. In this prospective, randomized trial, 27 women with PCOS underwent a total of 25 cycles of hMG alone and 33 cycles with adjunctive GnRH-a (leuprolide) treatment. Premature luteinization was seen less frequently in the leuprolide-treated cycles than in cycles treated with hMG alone. There were no differences between the treatments in ovarian sensitivity to hMG. Cycle fecundity was 0.16 for hMG alone cycles, and 0.27 for leuprolide with hMG cycles, which were not statistically different. We conclude that the sensitivity of the PCOS ovary to hMG is not affected by 4 weeks of leuprolide pretreatment. Longitudinal ultrasonographic study of the ovarian suppressive activity of a low-dose triphasic oral contraceptive during correct and incorrect pill intake Hami1tonC.J.C.M.; Hoogland H.J. Department of Obstetrics and Gynecology, Academic Hospital, P.O. Box 1918, 6201 BXMaastricht, NLD AM. J. OBSTET. GYNECOL. 1989, 16115 (1159-1162) A longitudinal study was conducted to evaluate the ability of a low-dose triphasic oral contraceptive to suppress ovulation as documented by frequent ultrasonographic scanning and progesterone determinations, even in the event of a missed pill. The extent of follicular growth and maturation, the incidence of escape ovulation, and the effect of correct and incorrect pill intake were assessed in 30 evaluable women during two consecutive spontaneous menstrual cycles. After the first cycle, 11 of 30 women (36.6%) had follicle-like structures of at least 10 mm in diameter. Ten of 11 structures gradually disappeared during the second cycle, with one persistent structure remaining through the second cycle. Seven of 30 women (23%) developed follicle-like structures during the second cycle. Of these, one woman had a probable ovulation, and another had an elevated progesterone level without follicle rupture, suggesting the luteinized unruptured follicle syndrome. Both of these women missed a pill on day 1 of the second cycle. In all cases cervical scores indicating hostility were noted. Thus, although suppression of ovarian activity may have been incomplete when oral contraceptives were incorrectly taken, secondary mechanisms of contraception remained operant. Low-dose triphasic oral contraception consistently prevented ovulation. Estrogerdc action of tamoxifen in women treated with luteinizing hormone-releasing hormone agonists (goserelin). Lack of shrinkage of uterine fibroids Lumsden M.A.; West C.P.; Hillier H.; Baird D.T. Department of Obstetrics and Gynaecology, University of Edinburgh, Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9E W, GBR FERTIL. STERIL. 1989,52/6 (924-929) Six premenopausal women with uterine fibroids were treated with a combination of tamoxifen, 20 mg/d, and goserelin, 3.6 mg every 28 days, for a total of 24 weeks. Results were compared with those from six women, matched for pretreatment uterine volume, who had been treated with goserelin alone. Int J Gynecol Obstet 32
During combined therapy, plasma and urinary estrogen concentrations were significantly lower than during goserelin alone, whereas sex hormone binding globulin concentrations were significantly higher. Plasma luteinizing hormone and follicle stimulating hormone (FSH) concentrations were both suppressed, in contrast with results during goserelin alone when FSH levels remained within the pretreatment range. None of the women on combined therapy bled in response to the endocrine changes of the initial treatment cycle. Despite this profound pituitary-ovarian suppression, there was no significant change in uterine volume during combined therapy. These results suggest that tamoxifen is acting as an estrogen agonist in women rendered hypoestrogenic with luteinizing hormone-releasing hormone agonists. Nocturnal melatonin levels are unaltered by ovarian suppression in girls with central precocious puberty Berga S.L.; Jones K.L.; Kaufmann S.; Yen S.S.C. University of California, San Diego School of Medicine (T002), San Diego, CA, USA FERTIL. STERIL. 1989,52/6 (936-941) Girls with central precocious puberty were utilized as a model in which to study the melatonin secretory response to ovarian suppression. Eight girls with central precocious puberty documented by clinical and endocrine characteristics, including sleep-entrained augmentation of luteinizing hormone (LH) pulsatility, were investigated. Nocturnal (6:00 P.M. to 9.00 A.M.) plasma melatonin levels were measured hourly by a sensitive and specific radioimmunoassay before and after gonadotropin-ovarian downregulation with gonadotropinreleasing hormone (GnRH)-agonist. Although nocturnal melatonin elevations varied widely between girls, patterns within the same individual were remarkably reproducible and unaltered before and after treatment. Although estrogens have been shown to modulate melatonin synthesis and secretion, in this model, reduction of estrogen levels was not associated with alterations in plasma melatonin concentrations.
PREGNANCY, DELIVERY Cocaine abuse during pregnancy: Correlation between prenatal care and perinatal outcome MacGregor S.N.; KeithL.G.; Bachicha J.A.; Chasnoff I.J. Department of Obstetrics and Gynecology, Northwestern University Medical School, Chicago, IL, USA OBSTET. GYNECOL. 1989,74/6 (882-885) Cocaine abuse during pregnancy has been associated with increased perinatal morbidity and mortality regardless of the quantity or quality of prenatal care. In this study, we tested the hypothesis that among cocaine-abusing women delivering at the same institution, those receiving comprehensive prenatal care have better perinatal outcome than those receiving little or no prenatal care. Between January 1, 1984 and July 1, 1987, 120 pregnant women who abused cocaine received multidisciplinary prenatal care in the Perinatal Center for Chemical Dependence of Northwestern University (group 1). During this
Citations from the Literature same period, we identified 21 cocaine-abusing parturients at our institution who were not enrolled in the Perinatal Center for Chemical Dependence and who received little or no prenatal care (group 2). Control subjects were selected from the general obstetric population for comparison. Data from these two groups were compared with each other and with matched control pregnancies. Group 2 pregnancies had lower mean gestational age at delivery, lower mean birth weight, and a higher incidence of preterm delivery than group 1 pregnancies. Furthermore, groups 1 and 2 were significantly different from control pregnancies for these parameters. We conclude that comprehensive prenatal care may improve outcome in pregnancies complicated by cocaine abuse; however, the perinatal morbidity associated with cocaine abuse cannot be eliminated solely by improved prenatal care. Bias against the null hypothests: The reproductive hazards of cocaine Koren G.; Shear H.; Graham K.; Einarson T. Motherbk Programme, Department of Pediatrics, Divkion of CIinical Pharmacology, Hospitai for Sick Children, 555 University Avenue, Toronto, M5G IX8 Ont., CAN LANCET 1989,2/8677 (1440-1442) To examine whether studies showing no adverse effects of cocaine in pregnancy have a different likelihood of being accepted for presentation by a large scientific meeting, all abstracts submitted to the Society of Pediatric Research between 1980 and 1989 were analysed. There were 58 abstracts on fetal outcome after gestational exposure to cocaine. Of the 9 negative abstracts (showing no adverse effect) only 1 (llolo) was accepted, whereas 28 of the 49 positive abstracts were accepted (57%). This difference was significant. Negative studies tended to verify cocaine use more often and to have more cocaine and control cases. Of the 8 rejected negative studies and the 21 rejected positive studies, significantly more negative studies verified cocaine use, and predominantly reported cocaine use rather than use of other drugs. This bias against the null hypothesis may lead to distorted estimation of the teratogenie risk of cocaine and thus cause women to terminate their pregnancy unjustifiably Maternal
phenylketonuria and hyperphenylalaninemia: for medical practice in the United States Luder AS.; Green C.L. Inherited Metabolic Diseases Clinic, University of Colorado Health Sciences Center, Box CZ33, 4200 E. 9th Ave., Denver, CO 80262, USA AM. J. OBSTET. GYNECOL. 1989, 161/5 (1102-1105) The risk of maternal phenylketonuria and hyperphenylalaninemia syndrome, a preventable cause of severe birth defects and retardation with a near 100% recurrence risk if untreated, is increasing in the United States. The reasons for this are reviewed. Women with hyperphenylalaninemia and those with phenylketonuria diagnosed and treated at birth are intellectually normal, as are some women with undiagnosed phenylketonuria. Both groups are at risk for maternal phenylketonuria syndrome in their offspring if blood Implications
297
phenylalanine levels are not controlled by diet during pregnancy. The problems and pitfalls of suspecting, diagnosing, and managing the condition are discussed. Suggested strategies for reversing the increasing trend include the greater use of genetic registers, increased clinical awareness, and some form of rescreening. The advantages and costs of rescreening a subset of pregnant women or all pregnant women at or before their first registration are examined. Amniotic fhdd particles: Are they related to a mature amniotic flnid phospholipid profile? Helewa M.; Manning F.; Harman C. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Manitoba, Winnipeg, Man., CAN OBSTET. GYNECOL. 1989,74/6 (893-896) In a prospective, blinded clinical study, the relationship between amniotic fltid free-floating particles measured by a dynamic ultrasound imaging method and phospholipid profile was studied in 82 women undergoing amniocentesis between 26 -42 weeks’ gestation. None of 11 patients with sonographitally clear amniotic fluid had a mature phospholipid profile (lecithin-sphingomyelin ratio greater than 2 and detectable phosphatidylglycerol). Thirty-eight of 71 women (53W) with turbid or markedly turbid amniotic fluid had a mature phospholipid profile. The sensitivity of this method was lOO%, specificity 25%, positive predictive value 53%, and negative predictive value 1OOolo.Although the Ending of sonographitally clear amniotic fluid may eliminate unnecessary amniocentesis, markedly turbid amniotic fluid is not a reliable indicator or a mature amniotic fluid phospholipid profile. Examination of amniotic fluid in diagnosing congenital syphilis with fetal death Wendel G.D.; Maberry M.C.; Christmas J.T.; Goldberg M.S.; Norgard M.V. Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dollas, TX 75235, USA OBSTET. GYNECOL. 1989,74/6 (967-970) The diagnosis of congenital syphilis is difficult, particularly in stillborn fetuses, who are often macerated and have undergone autolysis. These changes can obscure both syphilitic histology findings and special stains for spirochetes in tissue specimens used to confirm the diagnosis of congenital syphilis. Five gravidas with untreated syphilis and fetal deaths underwent sonographic examination and amniocentesis. In all five cases, dark-field microscopic examination of the amniotic fluid showed spirochetes with morphology and motility characteristics of Treponema pallidum. Organisms were infrequent, but easily identified at 400 x magnification and confirmed using an oil-immersion objective yielding a 900 x magnification. After delivery, fetal-placental examination and autopsy showed clinical findings typical of congenital syphilis in all five cases. Histologic changes compatible with syphilis were found in all four autopsied fetuses. Silver impregnation stains were positive in two of five tissue specimens, and anti-treponemalmonoclonal antibody immunofluorescence assays were positive Int J Gynecol Obstet 32