Tariq A. Siddiqi

Progression of diabetic retinopathy in pregnancy: association with hypertension in pregnancy.

OBJECTIVE To test the hypothesis that women with insulin-dependent diabetes and chronic or pregnancy-induced hypertensive disorders are at increased risk for developing retinopathic complications during pregnancy. STUDY DESIGN One hundred fifty-four women with insulin-dependent diabetes were prospectively followed in an intensive program of diabetes in pregnancy. Ophthalmologic evaluations were obtained through pregnancy and at 6 to 12 weeks post partum, and findings were graded by a standard scale. Association of retinopathic progression with risk factors was tested with chi 2 and multiple logistic regression analysis. RESULTS Fifty-one women had progression of retinopathy during pregnancy; postpartum regression was observed in 13 women. Changes in glycemic control early in pregnancy, chronic hypertension, and pregnancy-induced hypertension were significantly associated with progression of retinopathy. CONCLUSION Women with insulin-dependent diabetes who have hypertensive disorders in pregnancy are at increased risk for progression of retinopathy.

A focused preconceptional and early pregnancy program in women with type 1 diabetes reduces perinatal mortality and malformation rates to general population levels

OBJECTIVE To evaluate the impact of a focused preconceptional and early pregnancy program specializing in the care of women with Type 1 diabetes on perinatal mortality and congenital malformations. METHODS This clinical study included women with Type 1 diabetes in an interdisciplinary Diabetes in Pregnancy Program Project Grant (PPG) funded by the NIH (1978-1993); these women were enrolled preconceptionally or during the first trimester (up to 14 weeks) and had pregnancies continuing beyond 20 weeks gestation. Strict glucose control was implemented and adherence assessed. Antepartum fetal surveillance was started at 32 weeks gestation. All live-born infants and stillbirths were examined. A retrospective comparison analysis of the period before PPG I (1973-1978) and after cessation of funding (1993-1999) was performed, specifically evaluating perinatal mortality and congenital malformation rates. Data were analyzed using analysis of variance, chi2, and Fishers exact test. RESULTS Three hundred and six women were enrolled in three 5-year periods: PPG I (1978-1983) n = 111, PPG II (1983-1988) n = 103, and PPG III (1988-1993) n = 92. Entry and interval glycohemoglobin A1 concentrations obtained decreased with each consecutive PPG. An emphasis on preconception care began in 1984, with preconception enrollment reaching 23% for PPG II and increasing in PPG III to 37%. As preconception enrollment increased, perinatal mortality rate decreased from 3% for PPG I and 2% for PPG II, to 0% in PPG III, and the congenital malformation rate decreased to a low 2.2% by PPG III. Comparison data collected for the period before PPG 1 (1973-1978) n = 79 revealed a perinatal mortality rate of 7% and a congenital malformation rate of 14%. Also, a postprogram retrospective analysis of the period 1993-1999 (n = 82) revealed an increase in perinatal mortality, with one death compared to none in PPG III, and a congenital malformation rate of 3.65% compared to 2.2% during PPG III. The preconception enrollment for this period decreased (19.5%). CONCLUSIONS A program emphasizing preconceptional care, strict glycemic control preconceptionally and throughout gestation, and the use of antepartum fetal surveillance was associated with a significant decrease in the rate of perinatal mortality and congenital malformations in infants of women with Type 1 diabetes. However, ongoing improved outcome appears to depend on the availability of funding for a specialized preconception program.

Major malformations in Infants of IDDM Women: Vasculopathy and Early First-Trimester Poor Glycemic Control

From animal and in vitro studies, it has been suggested that high environmental glucose, ketone, or insulin concentrations and low glucose or insulin concentrations may be etiologic factors for congenital malformations (CMs) in infants of diabetic mothers (IDMs). Transplacental passage of antibody-bound insulin has been demonstrated in humans. Controversy exists regarding the pathophysiology of CMs in human insulin-dependent diabetes mellitus (IDDM) pregnancies. We hypothesized that CMs in IDMs are associated with maternal vasculopathy, poor first-trimester glycemic control (i.e., hyper- and/or hypoglycemia), advanced White class, and high insulin requirements. We studied 165 first pregnancies of women with IDDM from 1978 to 1986. The goals of glucose control were a fasting blood glucose of <100 mg/dl and a 90-min postprandial blood glucose of <140 mg/dl. Insulin requirements, body weight, and pre- and postprandial blood glucose were recorded at weekly clinic visits. Maternal blood HbA1 was measured on entry and every 4 wk to confirm that adequate glycemic control was achieved. Women who enrolled in the project were interviewed during gestation by a geneticist/dysmorphologist who obtained genetic and environmental histories using a standard questionnaire. All live-born infants and stillbirths were examined. Each live-born infant was assessed systematically by two independent examiners, a neonatologist and a geneticist/dysmorphologist; examination with standardized checklists was performed in the newborn nursery as soon after birth as was practical. In first pregnancies in the study, there were 13 IDMs with major CMs (7.9%). By both univariate and multivariate analyses, the following two factors were significantly associated with major CMs: preexisting vasculopathy (retinopathy and/or nephropathy; 54 vs. 25% in the CM and non-CM groups, respectively; P < .05) and increased maternal HbA, at 9 wk gestation (P < .001). CMs were not associated with White class, insulin requirements, and frequency of maternal hypoglycemia as assessed clinically. There was no significant interaction between maternal HbA, and the presence of vasculopathy. We conclude that maternal vasculopathy and poor glycemic control during embryogenesis, but not frequency of maternal clinical hypoglycemia or insulin therapy per se are independent factors associated with major CMs in IDMs. We suggest, based on these data, that in addition to establishment of meticulous glycemic control, IDDM women be assessed for vasculopathy before pregnancy and given appropriate counseling regarding risk of CMs.

Neonatal polycythemia in infants of insulin-dependent diabetic mothers.

&NA; The rate of neonatal polycythemia was determined prospectively in 34 infants of diabetic mothers pair‐matched to 34 infants of nondiabetic mothers (control group) for site of sampling, time of sampling, time of cord clamping, gestational age, mode of delivery, and one‐ and five‐minute Apgar scores. Polycythemia (venous hematocrit greater than or equal to 65%) was present in 29.4% of infants of diabetic mothers and 5.9% of control subjects (P < .03). Mean nucleated red blood cell counts were significantly higher in infants of diabetic mothers than in controls. Polycythemia did not correlate with higher maternal hemoglobin A1 concentration or with increased infant weight percentile, but did correlate with neonatal hypoglycemia. The authors speculate that increased erythropoiesis exists in infants of diabetic mothers and might be subsequent to fetal hypoxemia due to fetal hyperglycemia, hyperinsulinism, and hyperketonemia. (Obstet Gynecol 68:370, 1986)

American Institute of Ultrasound in Medicine consensus report on potential bioeffects of diagnostic ultrasound: Executive summary

The continued examination of potential biological effects of ultrasound and their relationship to clinical practice is a key element in evaluating the safety of diagnostic ultrasound. Periodically, the American Institute of Ultrasound in Medicine (AIUM) sponsors conferences bringing experts together to examine the literature on ultrasound bioeffects and to develop conclusions and recommendations related to diagnostic ultrasound. The most recent effort included the examination of effects whose origins were thermal or nonthermal, with separate evaluations for potential effects related to fetal ultrasound. In addition, potential effects due to the introduction of ultrasound contrast agents were summarized. This information can be used to assess risks in comparison to the benefits of diagnostic ultrasound. The conclusions and recommendations are organized into 5 broad categories, with a comprehensive background and evaluation of each topic provided in the corresponding articles in this issue. The following summary is not meant as a substitute for the detailed examination of issues presented in each of the articles but rather as a means to facilitate further study of this consensus report and implementation of its recommendations. The conclusions and recommendations are the result of several rounds of deliberations at the consensus conference, subsequent review by the Bioeffects Committee of the AIUM, and approval by the AIUM Board of Governors.

Perinatal asphyxia in infants of insulin-dependent diabetic mothers†

Infants of diabetic mothers are thought to be at risk for perinatal asphyxia. We hypothesized that the following are significant risk factors for perinatal asphyxia: poor third-trimester glycemic control, diabetic vascular disease (nephropathy, retinopathy) appearing in pregnancy, pregnancy-associated hypertension, smoking, prematurity, fetal macrosomia, and maternal hyperglycemia and hypoglycemia within 6 hours preceding delivery. We prospectively studied 162 infants born to 149 diabetic mothers (White classes B through R-T). Perinatal asphyxia was defined clinically as fetal distress during labor (late decelerations, persistent fetal bradycardia, or both), 1-minute Apgar score less than or equal to 6, or intrauterine fetal death. Forty-four infants (26.7%) had perinatal asphyxia. The presence of perinatal asphyxia did not correlate with third-trimester glycemic control, pregnancy-associated hypertension, smoking, fetal macrosomia, or maternal hypoglycemia before delivery, but it did correlate significantly with nephropathy appearing in pregnancy, maternal hyperglycemia before delivery, and prematurity. We speculate that (1) the appearance of diabetic vasculopathy (nephropathy) during pregnancy is accompanied by placental vascular disease and subsequently by fetal compromise and (2) in pregnancy complicated by diabetes, maternal and subsequently fetal hyperglycemia before delivery leads to fetal hypoxemia.

Transforming growth factor-β1 expression during placental development

Abstract Placental growth has several malignant characteristics, including properties of invasiveness, rapid cell proliferation, and a lack of cell contact inhibition. These malignant characteristics of placental development are strictly regulated throughout normal gestation, because placental growth is limited in both extent and duration. Transforming growth factor-β 1 , inhibits growth of many normal and malignant cell lines. In this study, using Northern blot analysis, we found transforming growth factor-β 1 expression to occur in human placenta throughout gestation. Peak expression was noted at midgestation (near 17 weeks) and again in late gestation (near 34 weeks). Immunohistochemical analysis localized transforming growth factor-β 1 protein expression to the syncytiotrophoblastic layer. The process of trophoblastic invasion of the decidua and myometrium is usually complete by 18 weeks of gestation, and absolute growth of the placenta ceases in late gestation (near 35 weeks). The time frames of maximal transforming growth factor-β 1 , expression noted in our studies correlate with these events. We speculate that peak transforming growth factor-β 1 , expression at these stages of placental development is suggestive of its regulation of both trophoblastic invasion and proliferation.

Changes in activity of cytosolic phospholipase A2 in human amnion at parturition

OBJECTIVE The purpose of this study was to determine whether increased cytosolic phospholipase A2 activity mediated arachidonic acid mobilization for prostaglandin synthesis in amnion at parturition. STUDY DESIGN Amnion was collected immediately after delivery from four groups of patients: preterm (<37 weeks) with no labor or labor and term (>37 weeks) with no labor or labor and stored at -70 degrees C. Tissues were homogenized and centrifuged for 1 hour at 100,000 g, and cytosol was assayed for cytosolic phospholipase A2 activity with use of carbon 14-labeled 1-stearoyl-2 arachidonyl phosphatidylcholine plus 10 micromol/L unlabeled substrate and 5 mmol/L calcium in 10 mmol/L N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid, pH 7.4. Incubations were performed in duplicate +/- 10 micromol/L arachidonyl trifluoromethyl ketone, a specific inhibitor of cytosolic phospholipase A2 activity, at 30 degrees C for 45 minutes. RESULTS Total cytosolic phospholipase A2 activity (in picomoles of arachidonic acid per minute per milligram of protein) calculated as the difference between the activity in the presence and absence of arachidonyl trifluoromethyl ketone was (mean +/- SE) as follows: preterm no labor (n = 7) 8.94 +/- 3.08, preterm with labor (n = 6) 6.79 +/- 2.31, term no labor (n = 7) 14.85 +/- 1.66, and term with labor (n = 5) 5.51 +/- 1.52. Enzyme activity increased with gestational age and was highest in the term no labor group. A significant decrease in cytosolic phospholipase A2 activity occurred with labor (p < 0.05). The greatest decrease in activity was in the term group (p < 0.05). CONCLUSION Total cellular cytosolic phospholipase A2 activity in amnion is highest in anticipation of labor but during labor total activity is depleted, resulting in the low activity measured after delivery of the placenta. The substrate specificity and changes in amnion total cytosolic phospholipase A2 activity with labor strongly suggests a role in mediation of arachidonic acid mobilization and prostaglandin synthesis at labor.

Placental transfer of ganciclovir in a woman with acquired immunodeficiency syndrome and cytomegalovirus disease

A pregnant woman with AIDS developed cytomegalovirus (CMV) retinitis and pneumonitis, requiring intravenous ganciclovir. At 34 weeks gestation the woman delivered a 1.4-kg girl. Examination of the placenta revealed transplacental passage of CMV. Low concentrations of ganciclovir were detected in the neonates plasma. The neonate had mild anemia but no other signs of congenital CMV infection.

The effect of early discharge after vaginal delivery on neonatal readmission rates

Objective To determine the effect of a structured program for early neonatal discharge from a tertiary medical center on the risk of neonatal readmission. Methods An early-discharge program was instituted at our tertiary medical center in July 1993, with the objective of discharging mothers and infants within 24 hours after vaginal birth. The readmission rate of vaginally delivered infants during the early-discharge period (July 1, 1993, through March 31, 1995) was compared with the rate during a conventional-discharge period (January 1, 1992, through June 30, 1993). Analyses were performed to examine two groups within the early-discharge group: those discharged within 24 hours of vaginal delivery; and those discharged within 1 hospital day of vaginal delivery. Results During the early-discharge period, 1.24% of neonates were readmitted within 10 days of birth, compared with 1.35% during the conventional-discharge period. In the early-discharge period group, infants born vaginally and discharged within 24 hours of birth had a readmission rate of 1.46% compared with 1.14% for those who stayed longer than 24 hours after delivery. Similarly, the readmission rate was no different for infants who were discharged within 1 hospital day. The primary indications for readmission in both periods were infections and jaundice. Conclusion Implementation of a structured program for early neonatal discharge does not have an association with increased risk of neonatal readmission to the hospital.