Alcohol abuse--a persistent preventable risk for congenital anomalies.

OBJECTIVE: To examine whether alcohol abuse (ALC) continued to be a health hazard to pregnant women in the 1990s. STUDY DESIGN: Analysis of a perinatal data base comprising 170,258 women with singleton pregnancies. Univariate cross table analysis and logistic regression were conducted to examine the association between alcohol abuse and congenital malformations coded according to the International Classification of Diseases (ICD). RESULTS: 14,727/170,258 mothers (8.6%) admitted to ALC during pregnancy and 36,705/170,258 (21.6%) to smoking. Anomaly rates for ALC (365/14,092, 4.3%) vs. Non-ALC (6187/149,344, 4.0%) differed significantly (p<0.001). The rates of specific anomalies varied between <0.1% and 1.1%. Odds ratios for 16 ICD 9 anomaly categories were >1 in 14 instances overall (Sign test, p=0.004), in 12 instances in women <30 years (p=0.08), and in 13 instances in women over 30 years (p=0.02). Congenital anomalies of the "respiratory system" (ICD9 748), of "genital organs" (ICD9 752.1), of the "integument" (ICD9 757), and "other anomalies of limbs/other musculoskeletal anomalies" (ICD 755/756) were statistically significantly associated with ALC, especially in women>30 years. CONCLUSION: ALC in pregnancy continued to be an important factor independently associated with an increased incidence of a broader range of congenital anomalies than previously recognized. Risk for anatomic anomalies was increased in offspring of ALC women over age 30, consistent with previous reports of increased risk of neurobehavioral abnormality in offspring of women over 30.

Parental decisions to terminate/continue following abnormal cytogenetic prenatal diagnosis: "what" is still more important than "when".

This study was undertaken to determine if parental decisions to continue or terminate following the diagnosis of a cytogenetic abnormality have changed over the past 8 years at the same center. Parental decisions in 310 prenatal chromosomal abnormalities were stratified by procedure (chorionic villus sampling [CVS] vs. amniocentesis) and the severity of the anomaly (severe vs mild-moderate). Patients with severe anomalies were much more likely to terminate regardless of gestational age. There was a trend (P = .107) toward a lower rate of termination for mild-moderate degrees in the second trimester. There was no change in patient's decisions over time. Patients' decisions about termination are focused on the severity of the disorder and only marginally influenced by when in gestation the decision is made.

Histopathology of fetal diastrophic dysplasia.

We report on three cases of diastrophic dysplasia in second trimester fetuses and discuss the differential diagnosis and clinical, radiologic, and histopathologic findings. Manifestations of typical diastrophic dysplasia in infants and older patients include abnormal pinnae, scoliosis, and joint contractures; these were absent in the fetuses, in keeping with the tendency for the clinical and radiologic aspects of this disease to become more severe with age. The histopathologic characteristics of the cartilage appear to be similar in the fetus and older patient, and therefore may be useful in differentiating diastrophic dysplasia from other osteochondrodysplasias in the second trimester.

Differential increases in AFP, hCG, and uE3 in twin pregnancies: impact on attempts to quantify Down syndrome screening calculations.

Since the advent of multiple marker screening (MMS) for Down syndrome (DS) risk calculations, limitations for twins have been apparent. Recent attempts have been made to extrapolate mathematically singleton risks to twins. Here we investigate the pattern of levels among AFP, hCG, and uE3 in twins. MMS screening data from 4,443 twin pregnancies were compared to those from 258,885 singletons from 14-21 weeks of gestational age during a 3-year period (1992-1994) in our laboratory. Medians were determined for singletons and twins, and the ratios of twins to singletons were derived. Median AFP levels for twins are approximately double those of singletons, but median increases for hCG and uE3 are less than double. The data were divided further by ethnic groups (white, African American, Asian, and Hispanic), among which there were significant variations in medians, but not in the ratios of twins to singletons. The increased serum levels of different markers in twins are not consistent across analytes, possibly reflecting independent development of different compartments. Such differences mean that a mere mathematical conversion of singleton DS risks would be imbalanced among the analytes and cannot be applied reasonably to twins. Ethnic-specific databases are as important in twins as they are in singletons.

Aneuploidy among prenatally detected neural tube defects.

We have reported previously a 10% aneuploidy detection rate among 39 cases of fetal neural tube defects (NTD). Subsequently we amassed an additional experience of over 17,000 prenatal diagnosis cases over a 5-year period. During this period 106 cases of NTDs were identified; 44 with anencephaly, 62 with open spina bifida. The average maternal age of this population with NTDs was 29 years (15-40); 6 patients declined amniocentesis. Six of 100 cytogenetic studies were aneuploid; one anencephalic fetus had inherited a maternal marker chromosome, and 5 NTD cases had trisomy 18. The average maternal age of the aneuploid cases was 31 (19-40); 3 were 35 years or older. Four of 5 trisomy 18 cases had multiple congenital anomalies (MCA). The overall aneuploidy detection rate in our cohort was 5-6%, while aneuploidy occurred in 2% of the isolated NTD cases, and 24% of the MCA cases. Combining the earlier experience, 4/39 aneuploidy (2 trisomy 18, 4p+, del 13q) yields an aneuploidy detection frequency of 10/145 (7%), of which most (7/10) had trisomy 18. These data support fetal karyotyping for accurate diagnosis, prognosis, and recurrence-risk counseling.

Fetal compromise associated with extreme fetal bile acidemia and maternal primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis is a rare form of progressive biliary inflammation and fibrosis of unknown etiology that ultimately destroys the liver, leading to cirrhosis, liver failure, and death. Only one prior case has been reported in pregnancy. CASE: Our patient had the diagnosis of primary sclerosing cholangitis made 2 years before conception. Her course was remarkable for retroplacental hemorrhage at 14-16 weeks and preplacental hemorrhage at 28-34 weeks, with fetal growth retardation, spontaneous premature rupture of the membranes, meconium-stained amniotic fluid, fetal bradycardia, and peripartal exacerbations of her disease. Most uniquely, however, in our case the fetal compromise was associated with an extreme elevation of the bile acid level to greater than 2000 mg/dL in the fetal circulation. CONCLUSION: The extreme elevation of fetal bile acidemia at levels greater than 40 times normal in our case may well represent the pathophysiologic link between aberrations of maternal bile acid metabolism during pregnancy and fetal compromise.

Second-trimester minor ultrasound anomalies: impact on the risk of aneuploidy associated with advanced maternal age.

OBJECTIVE: To determine the impact of the presence or absence of minor ultrasound anomalies for the risk of aneuploidy in patients already at high risk because of advanced maternal age. METHODS: Eleven hundred forty-four women having amniocentesis for advanced maternal age were divided into those with minor ultrasound anomalies (n = 62) and those without (n = 1082). Two hundred fifty-nine women younger than 35 years but with minor anomalies on ultrasound were also included. RESULTS: Fetal aneuploidy was found in six of 62 (9.7%) women of advanced maternal age with minor ultrasound anomalies, in five of 1082 (0.5%) women older than 35 years with normal ultrasound results, and in five of 259 (1.9%) women younger than 35 years with minor ultrasound anomalies. CONCLUSION: Minor ultrasound anomalies increase considerably the risk of aneuploidy in women older than 35 years, and their absence lowers that risk slightly. Minor ultrasound anomalies in the fetuses of women younger than 35 raises their risk to that of a 39-year-old women in her second trimester. Ultrasound can be used to modify genetic risks at counseling and may help patients in their decision to have invasive testing.

Influence of gestational age and maternal height on fetal femur length calculations.

OBJECTIVE: To determine whether current methods of detecting Down syndrome based on fetal femur length calculations are influenced by gestational age or maternal height. METHODS: Four formulas were used to calculate expected femur length (FL) based on the fetal biparietal diameter (BPD) between 15 0/7 weeks' gestation and 19 6/7 weeks' gestation. For each gestational age, the BPD:FL ratio for women shorter than one standard deviation (SD) below the mean height was compared with the ratio for women taller than one SD above the mean height. A measured:expected FL ratio of 0.91 or less and a BPD:FL ratio greater than 1.5 SD above the mean was considered abnormal. RESULTS: The four formulas used to calculate measured:expected FL ratios were significantly more likely to be abnormal at 15--16 weeks' gestation, compared with 18-19 weeks' gestation (P <.05). Maternal height correlated with femur lengths at 18 and 19 weeks' gestation (P <.05) but not at earlier gestational ages. At 18 and 19 weeks' gestation, women shorter than one SD below the mean were twice as likely to have an abnormal BPD:FL ratio compared with women taller than one SD above the mean (relative risk 2.38; 95% confidence interval 1.21, 4.69). CONCLUSION: Early gestational age increases a woman's risk of having an abnormal measured:expected FL ratio, whereas short stature increases a woman's risk of having an abnormal BPD:FL ratio at later gestational ages. These findings indicate that risk assessment for fetal Down syndrome for such patients might be inaccurate. (Obstet Gynecol 2001;97:742-6.

Similarity of insulin-dependent diabetics' and non-insulin-dependent diabetics' levels of beta-hCG and unconjugated estriol with controls: no need to adjust as with alpha-fetoprotein.

OBJECTIVE: To determine if the same systematic alteration of serum values seen for alpha-fetoprotein (AFP) in diabetic patients is also seen for beta-hCG and unconjugated estriol (uE3). METHODS: Serum AFP, beta-hCG, and uE3 results were obtained in 18,639 patients for whom complete follow-up information was obtained. Patients were divided into euglycemic (n = 18,088), insulin-requiring diabetics (n = 104), and non-insulin-requiring diabetics (n = 437), as well as by race. RESULTS: The 20% adjustment used for AFP appropriately corrects serum values. No such systematic variation is seen for either beta-hCG or uE3 by glycemic status or race. CONCLUSION: No adjustment for beta-hCG or uE3 is necessary for diabetes for biochemical screening programs.

Cocaine and development: mechanisms of fetal toxicity and neonatal consequences of prenatal cocaine exposure.

As cocaine use during pregnancy has become increasingly recognized, there also has been increased concern about the toxic and teratogenic properties of cocaine on the fetus. A significant literature exists describing the adverse fetal and neonatal outcomes associated with in utero cocaine exposure. However, specific causality by cocaine on outcome in the human is difficult to ascertain because of multiple confounding variables associated with substance abuse including social factors and polydrug use as well as difficulty in confirming timing, dose and frequency of cocaine exposure. Most literature suggests that prenatal cocaine exposure is associated with developmental risk to the fetus. What is currently unknown is the extent of risk, the additive and/or synergistic factors contributing to cocaine's toxicity and the reversibility of the injury. In this paper we review the pharmacologic properties of cocaine as related to a model of mechanisms for developmental injury secondary to cocaine exposure and the published literature on the adverse fetal and neonatal outcomes associated with cocaine use during pregnancy. Specific attention has been focused on the structural, neurobehavioral and respiratory control teratogenesis.

Maternal cocaine addiction and fetal behavioral state. I: A human model for the study of sudden infant death syndrome.

Abnormalities of respiratory regulation, such as apnea and abnormal hypoxic arousal during sleep, are mechanistic in the pathophysiology of SIDS. In utero cocaine exposure is associated with poor head growth, abnormal neurodevelopment, and an increased incidence of sudden, unexplained death, suggesting that in utero cocaine exposure disrupts the central regulation of breathing. It is likely that this disruption is due to altered CNS maturation. Indeed, cocaine alters norepinephrine metabolism within the locus coeruleus, important in arousal from sleep, suggesting that the increased incidence of SIDS in cocaine exposed infants may be secondary to sleep-related deficits in arousal. Since components of fetal behavioural state organization reflect the successful integration of the Central Nervous System, have a specific developmental timetable, and can be studied by fetal ultrasound techniques, we developed a strategy for assessing the state organization of the fetus by ultrasound techniques. We hypothesize that fetal evaluation of state will be a marker of abnormal CNS maturation and a predictor of risk, i.e. abnormal neurodevelopment and/or state related arousal deficits predisposing the cocaine exposed neonate to SIDS. We propose that the study of in utero cocaine exposed fetuses will provide a human model for examining the pathophysiology of SIDS.

Selective reduction for multifetal pregnancy. Early opinions revisited.

Multifetal pregnancy reduction has emerged as a staple of infertility therapy. With increasing utilization of aggressive infertility therapies, thousands of couples have been able to achieve pregnancies who otherwise would not have, but an increasing number and proportion of patients have multifetal pregnancies. Multifetal pregnancy reduction (MFPR) has been shown to be a safe and effective treatment for reducing the number of pregnancies, thereby reducing both perinatal morbidity and mortality in resultant pregnancies. The world experience suggests that the risks of MFPR are directly related to the starting number of fetuses but that in the majority of instances, healthy children can be achieved.

Impact of prenatal care with reduced frequency of visits in a residency teaching program.

OBJECTIVE: To determine if decreasing the number of prenatal visits for routine obstetric patients affects pregnancy outcome. STUDY DESIGN: A historical control study was designed to include 734 deliveries from January 1 to December 31, 1991, in women who had prenatal care per American College of Obstetricians and Gynecologists Committee Opinion no. 79, January 1990, guidelines for uncomplicated obstetric care. A prospective study cohort of women with 711 deliveries from January 1 to December 31, 1994, underwent prenatal care with modified guidelines to include: first visit at 6-12 weeks to confirm dating and obtain initial laboratory data, second visit at 16-20 weeks to obtain maternal serum alpha-fetoprotein screening, third visit at 24-28 weeks for 28-week laboratory data, fourth visit at 32 weeks, fifth visit at 36 weeks, sixth visit at 38 weeks, seventh visit at 40 weeks and weekly thereafter. Pregnancy outcomes included estimated fetal weight, gestational age at delivery, preeclampsia, Apgar score at one and five minutes and delivery mode. Neonatal outcomes, including stillbirth rate, preterm delivery rate, intraventricular hemorrhage rate, bronchopulmonary dysplasia and neonatal mortality, were evaluated. RESULTS: There were no statistically significant differences in perinatal or neonatal outcomes with decreased prenatal visits from an average of 12 per pregnancy to 8. CONCLUSION: Prenatal visits can be decreased in a teaching hospital in women with uncomplicated pregnancies from the standard number, 12-14 visits, to an average of 7 or 8 per patient without adverse perinatal outcomes.

Development of a core curriculum in professional growth: practice management military model.

Military medicine has faced some big challenges in recent years. Military treatment facilities have not been exempt from these alterations, as the American public has sought to reinvent government practices with regard to medicine. Until recently, professional education consisted almost entirely of emphasis in the particular content of the chosen field. Obstetrics and gynecology was one of the first medical specialties to recognize the importance of practice management, professional growth and development, and to require exposure to it as part of the residency process. The Department of Obstetrics and Gynecology's instructional objectives dealing with professional growth and development originated as part of the military-unique curriculum for physicians implemented at Tripler Army Medical Center in Hawaii. Later, these objectives were used at Madigan Army Medical Center in Tacoma, Washington. Recent changes in the health care environment, coupled with an increasing awareness of professional liability and the newer specter of managed care, force physicians to learn the cost of each health encounter and to be more familiar with the business aspects of health care. As medicine in general is changing, the curricula have been revised and tailored to the needs of our physicians with the addition of ethics, managed care, utilization, and practice management.

Integrated Obstetric Curriculum for Obstetrics and Gynecology Residency, Radiology Residency and Maternal-Fetal Medicine Fellowship program at an accredited American Institute of Ultrasound in Medicine Diagnostic Ultrasound Center.

OBJECTIVE: The purpose of this work was to demonstrate the approach to developing an integrated curriculum for obstetric ultrasound training by utilizing an accredited American Institute of Ultrasound in Medicine teaching platform. METHODS: During the 1996-98 academic years, the American College of Obstetricians and Gynecologists and American Institute of Ultrasound in Medicine guidelines for ultrasound performance and training were integrated into a multifaceted training program for obstetric and radiological residents and maternal-fetal medicine fellows consisting of a structured reading program, self study of a 35-mm slide program of normal/abnormal anatomy, a basic ultrasound and fetal echocardiography interactive CD program, hands-on supervised scanning program and practical and certificate-bearing fetal echocardiography courses for fellows. All obstetric residents were given pretests and post-tests to measure learning performance in the program. The results from these tests were analyzed for statistical significance. RESULTS: Thirteen obstetric residents completed the training program. The locally developed pretest showed a mean of 16/40 correct questions with an SD of 1.85. After completing the training, the mean obstetric resident scores on the post-test were 32/40 with an SD of 5.9. This difference was statistically significantly different, P < 0.009. Radiology residents showed an improvement from no residents passing the obstetric ultrasound portion on the 1996 Radiology Boards to 100% pass rate in 1997 (four residents per year) after completing the course. Maternal-fetal medicine fellows progressed from inability to perform acceptable fetal echocardiography to full ability to perform fetal echocardiographic examinations. CONCLUSION: An integrated approach to obstetric ultrasound training for obstetric and radiologic residents and maternal-fetal medicine fellows with multifaceted learning methods is easily achieved with available guidance from the American College of Obstetricians and Gynecologists and American Institute of Ultrasound in Medicine.

Outcome of term gestation neonates whose mothers received intrapartum antibiotics for suspected chorioamnionitis.

Intrapartum antibiotics are commonly given to women suspected of having chorioamnionitis. However, there is no consensus regarding management of their babies. To date, there are no data concerning the clinical courses and outcomes of term gestation, "pretreated" neonates. We performed a retrospective review to assess the clinical courses of such infants. From 1987 to 1989, chorioamnionitis was diagnosed in 123 women, 102 of whom received intrapartum antibiotics. Of the 86 term gestation infants born to women in the latter group, 63 were completely asymptomatic. When compared with these neonates, the 23 symptomatic infants were more likely to have lower median 1 and 5 minute Apgar scores (3 vs 8 and 7 vs 9, respectively; p < 0.0001), higher immature:mature neutrophil ratios on their initial complete blood counts (0.48 vs 0.24; p = 0.0003), and positive urine antigen studies for group B Streptococcus in the presence of negative blood cultures (4 vs 2; p = 0.042). The intrapartum courses of those infants destined to be symptomatic were more likely to be complicated by fetal tachycardia (p = 0.049) and malodorous amniotic fluid (p = 0.005). Since more than 95% of asymptomatic, pretreated, term gestation neonates have a benign clinical course, aggressive evaluation and management of these infants may not be necessary.

Vasodilatory response of fetoplacental vasculature to adrenomedullin after constriction with the thromboxane sympathomimetic U46619.

OBJECTIVE: This study was undertaken to determine whether adrenomedullin, a hypotensive peptide, decreases vasomotor tone in fetoplacental vasculature that has been constricted with the thromboxane sympathomimetic U46619. STUDY DESIGN: The fetoplacental vascular beds of 20 perfused human placental cotyledons were vasoconstricted with a continuous infusion of U46619 (10(-8) mol/L). The vasculature was then sequentially injected with deionized water, 30 ng adrenomedullin, 300 ng adrenomedullin, and 3000 ng adrenomedullin. Any change in perfusion pressure was noted after each dose. In a separate experiment the fetoplacental vasculature in 2 perfused cotyledons from each of 10 placentas was vasoconstricted with U46619 (10(-8) mol/L). Adrenomedullin was infused continuously at either 200 ng/min (n = 5) or 2000 ng/min (n = 5) for 40 minutes. A corresponding control cotyledon from each placenta had isotonic sodium chloride solution added to its perfusion. Perfusion pressures were recorded every minute during the infusion and for 40 minutes afterward. Analysis of variance was used to compare pressure changes in the cotyledons that received bolus doses of adrenomedullin. Paired t tests of mean percentage pressure changes were used to compare the study and control groups that received the continuous infusions. RESULTS: In the cotyledons that received bolus doses of adrenomedullin, the mean (+/-SEM) percentage perfusion pressure changes from the baseline were -6.7 +/- 0.5 for 30 ng adrenomedullin (P =.0039), -8.5+/- 0.7 for 300 ng adrenomedullin (P <.0001), and -13.1 +/- 1.0 for 3000 ng adrenomedullin (P <.0001). With the continuous adrenomedullin infusion of 200 ng/min, there was no significant difference in the mean percentage pressure change from baseline between the study and control groups (-0.57%). At 2000 ng/min there was a significant difference (-15.34%; P <.0001). CONCLUSION: Adrenomedullin caused vasodilatation of fetoplacental vasculature previously constricted with the thromboxane sympathomimetic U46619 in the isolated perfused placental cotyledon. This vasodilatation occurred in a dose-dependent manner.

Multifetal pregnancy reduction.

Multifetal pregnancy reduction (MFPR) has become a mainstay of infertility therapy as its development has allowed physicians to become more aggressive in treating patients resistant to more conservative therapies. Over the course of the past decade, MFPR has become practised in a limited number of tertiary specialty centres, which have improved its performance and very substantially lowered its risks. The majority of physicians performing MFPR employ a transabdominal needle injection of potassium chloride into the fetal thorax. Risks for pregnancy losses of patients starting with triplets and/or quadruplets reduced to twins have improved over the past decade and are not substantially different from those in patients whose pregnancy began as twins. There have been no substantiated risks of coagulopathies or damage to surviving fetuses.

Intracranial cavernous angioma initially presenting in pregnancy with new-onset seizures.

A case of an intracranial cavernous angioma, which presented with headaches and seizures in a pregnant patient, is described. Diagnosis was established with magnetic resonance imaging. A computer-assisted literature search uncovered no previously reported case of intracranial cavernous angioma initially presenting during pregnancy.