Jonathan W. Weeks

Gestational diabetes: Does the presence of risk factors influence perinatal outcome?

OBJECTIVE Our purpose was to determine whether gestational diabetics with risk factors for gestational diabetes have worse glucose tolerance and poorer birth outcomes than those without risk factors. STUDY DESIGN We conducted a nonconcurrent cohort study of gestational diabetics identified by universal screening and delivered from Jan. 1, 1990, to Dec. 31, 1992. Multiple gestations and patients with chronic medical conditions were excluded. The following risk factors for gestational diabetes mellitus were abstracted: obesity (> 80 kg), family history of diabetes, previous gestational diabetes mellitus, and previous macrosomic, stillborn, or anomalous fetus. Patients with one or more risk factors were compared with those without risk factors. A group of low-risk nondiabetic patients served as controls. The incidences of A2 diabetes mellitus, cesarean section, neonatal macrosomia, and shoulder dystocia were the outcome variables of interest. RESULTS Selective screening would have failed to detect 43% of gestational diabetics. Twenty-eight percent of the missed gestational diabetics would have required insulin (class A2). When compared with controls, patients with gestational diabetes mellitus were at increased risk for macrosomia (26% vs 11%, p < 0.01), cesarean section (37% vs 15%, p < 0.01), and shoulder dystocia (9% vs 2%, p < 0.05). Patients with and without risk factors did not differ in mean maternal age, gestational age at delivery, birth weight, incidence of requiring insulin, macrosomia, or cesarean delivery. The similarities between those with and without risk factors remained after stratification by maternal age (> or = 30 years). CONCLUSION Gestational diabetics are at increased risk for adverse birth outcomes compared with low-risk controls. Class A2 diabetes mellitus and fetal macrosomia with its attendant risks are equally prevalent among patients with and without risk factors for gestational diabetes mellitus. Because > 40% of cases will be missed with selective screening, universal screening should be favored for detection of gestational diabetes mellitus.

Antepartum surveillance for a history of stillbirth: When to begin?

OBJECTIVE A history of stillbirth is universally accepted as an indication for antepartum fetal heart rate testing. Our goal was to examine when fetal testing should begin in an otherwise healthy patient with a history of stillbirth. STUDY DESIGN This is a nonconcurrent cohort study of patients who were seen for antepartum surveillance from January 1979 to December 1991 with a history of stillbirth as the only indication for testing. Subsequent pregnancies were evaluated for adverse outcomes and abnormal antepartum test results. RESULTS There was one case of recurrent stillbirth among the 300 study patients. Nineteen patients (6.4%) had one or more positive antepartum surveillance tests (positive contraction stress test or biophysical profile < or = 4). Three patients (1%) had positive tests before 32 weeks, all of whom were subsequently delivered without incident at term. Three patients were delivered for positive tests at < 36 weeks, one by cesarean section for fetal distress. We could not detect a relationship between the gestational age of the previous stillborn and the incidence of abnormal tests or fetal distress in subsequent pregnancies. CONCLUSION Antepartum surveillance should begin at > or = 32 weeks in the healthy pregnant woman with a history of stillbirth.

Persistence of penicillin G benzathine in pregnant group B streptococcus carriers

Objective To determine if streptococcicidal levels of penicillin G benzathine can be detected in maternal serum 4 weeks after treatment with 4.8 million units. Methods Thirty-seven pregnant women with positive group B streptococcus vaginal or urine cultures were each given 4.8 million units of penicillin G benzathine. Maternal blood samples were collected after injection and at delivery. Serum penicillin levels were measured by high-pressure liquid chromatography. Follow-up cultures were done when possible. Results None of the patients had serum penicillin levels below 0.20 μg/mL 30 days after treatment. Cord blood levels were approximately 50% lower than maternal levels. In all but three subjects, cord blood levels exceeded 0.06 μg/mL, the minimal inhibitory concentration for group B streptococcus. The three exceptions were patients who delivered more than 100 days after treatment. Group B streptococcus cultures were negative at the time of delivery in 72% of cases. None of the patients with positive cultures were moderately or heavily colonized. Conclusion In pregnant women, penicillin G benzathine levels are high enough to inhibit the growth of group B streptococcus for more than 4 weeks after injection with 4.8 million units. Further studies are needed to evaluate whether this regimen can prevent neonatal colonization and invasive group B streptococcus disease.

Antepartum Testing for Women with Previous Stillbirth

Women with past histories of stillbirth have been referred for antepartum surveillance since the inception of electronic fetal monitoring. However, this approach was originally based on mid-twentieth century perinatal studies that noted an increase in adverse outcomes in pregnancies subsequent to stillbirth. When these landmark studies were done, Rh immune globulin, ultrasonography, and other important medical advances had not yet occurred. This article discusses whether women who have suffered a past stillbirth remain at increased risk for perinatal mortality and morbidity in future pregnancies and whether antepartum fetal surveillance can reduce the risk of recurrent stillbirth.

ANALYSIS OF POLYCYCLIC AROMATIC HYDROCARBONS IN AMNIOTIC FLUID SAMPLES FROM SMOKERS AND NONSMOKERS

Previous studies from this laboratory have focused on the characterization of blood protein adducts formed in utero as a result of maternal smoking during pregnancy. These biological samples, obtained during the third trimester of pregnancy, at delivery, have clearly shown a correlation between maternal smoking histories and exposure of the fetus to tobacco smoke carcinogens, including 4-aminobiphenyl and benzo(a)pyrene. In the present study, we examined exposure of the fetus during the first trimester of pregnancy to various environmental carcinogens, particularly those found in tobacco smoke. Amniotic fluid samples were obtained from women undergoing routine amniocentesis between 16 and 20 weeks gestational age. Amniotic fluid, produced by the fetal lungs and kidneys, is an important part of pregnancy and fetal development and this fluid surrounds the fetus throughout pregnancy. In these studies, samples of amniotic fluid were obtained from nonsmokers as well as 0.5 pack per day smokers, 1.0 pack per day smokers, and greater than 2.0 pack per day smokers. Maternal smoking status was determined by questionnaire as well as assessment of amniotic fluid for cotinine via immunoassay. Amniotic fluid samples were extracted and analyzed for the presence of polycyclic aromatic hydrocarbons (PAHs). A clear correlation was found between levels of maternal smoking and PAHs in the amniotic fluid. Amniotic fluid 1-hydroxypyrene levels ranged from 1.54 ± 0.12 μ g/L in nonsmokers to 11.72 ± 0.67 μ g/L in women smoking greater than 2 pks/da, indicating approximately a 10X increase over nonsmokers. Similar results were found 3-hydroxybenzo(a)pyrene, 6-hydroxybenzo(a)pyrene, and 3,6-dihydroxybenzo(a)pyrene, metabolites of the carcinogen benzo(a)pyrene as well as with the 9-hydroxy and 9,10-dihydroxy metabolites of anthracene. The 5-hydroxymethyl metabolite of 5-methylchrysene was found to range in concentrations from 1.65 ± 0.11 μ g/L in nonsmokers to 12.67 ± 0.79 μ g/L in greater than 2 packs per day smokers. These results demonstrate that amniotic fluid can serve as a biological marker of exposure to tobacco related polycyclic aromatic hydrocarbons. Identification of potentially harmful compounds detected at an early stage of pregnancy may prevent subsequent exposures to the fetus and as a result decrease the risk of potential genotoxic as well as teratogenic events.