Terminal transverse limb defects with tethering and omphalocele in a 17 week fetus following first trimester misoprostol exposure.

We report a fetus from an elective termination at 17 weeks gestation following maternal ingestion of 1200 micrograms of misoprostol at 7 weeks of gestation. The fetus had abscence of the middle and distal phalanges of fingers 1, 3, 4 and 5 with tethering by thin strands of tissue on one hand, a below-knee amputation of one leg and omphalocele. There was absence of amnion on the chorionic surface of the placenta, a pathologic feature of early amnion rupture.

Cardiovascular malformations: changes in prevalence and birth status, 1972-1990.

Through an ongoing hospital-based active malformation surveillance program, we identified cardiovascular malformations (CVMs) in 3.3 per 1,000 liveborn and stillborn infants, and fetuses from pregnancies terminated electively during a 15-year period. We excluded the children of mothers who had planned delivery elsewhere, but were transferred for care of anomalies that had been detected in prenatal screening.

Adams-Oliver syndrome associated with cardiovascular malformations.

We describe two families with Adams-Oliver syndrome (AOS), an autosomal dominant malformation syndrome (MIM No. 10030), in which cardiovascular malformations (CVMs) have been reported previously. In the first family, twin boys and their mother had the typical digital and scalp defects of AOS with various obstructive CVMs of the left heart (bicuspid aortic valve, Shone's complex).

The Diabetes in Early Pregnancy Study: beta-hydroxybutyrate levels in type 1 diabetic pregnancy compared with normal pregnancy. NICHD-Diabetes in Early Pregnancy Study Group (DIEP). National Institute of Child Health and Development.

Objective: The objective was to assess relationships between beta-hydroxybutyrate (beta-OHB) level and pregnancy outcome in human pregnancy in light of the fact that high levels of beta-OHB cause malformations and growth retardation in in vitro studies.

Research Design And Methods: We analyzed beta-OHB in prospectively collected specimens from the National Institute of Child Health and Human Development-Diabetes in Early Pregnancy Study, in gestational weeks 6-12 in diabetic (n = 204-239) and nondiabetic (n = 316-332) pregnant women.

Results: Levels of beta-OHB in diabetic women were 2.

Prenatal anticonvulsant drug exposure: teratogenic effect on the dentition.

Prenatal exposure to anticonvulsant medication has been shown to cause craniofacial dysmorphology, prenatal growth retardation, hypoplastic nails and phalanges, and visceral abnormalities. In this study we examined maxillary and mandibular stone dental casts (45) and panoramic radiographs (39) from 45 individuals with ages 4.5 to 22.

Physiological reduction in fasting plasma glucose concentration in the first trimester of normal pregnancy: the diabetes in early pregnancy study.

Previous studies indicate that fasting plasma glucose decreases during gestation, but the timing and extent are not consistent from study to study. We had an opportunity to examine this question in the normal pregnancy cohort of women studied in the Diabetes in Early Pregnancy Study. Subjects were monitored to identify pregnancy by human chorionic gonadotropin testing, enrolled within 21 days of conception, and screened to rule out gestational diabetes at the juncture of the second and third trimesters.

The prenatal detection of significant alcohol exposure with maternal blood markers.

Objective: To examine the efficacy of a combination of 4 blood markers of alcohol use in detecting alcohol-abusing pregnant women.

Study Design: Two new markers of alcohol use, whole blood-associated acetaldehyde and carbohydrate-deficient transferrin, and 2 traditional markers of alcohol use, gamma-glutamyl transpeptidase and mean red blood cell volume, were measured in the blood of pregnant women. Each woman was interviewed about alcohol and drug use, medical and obstetric histories, and nutrition.

Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy.

Background: Misoprostol is commonly used to induce abortion in Brazil, and in other countries in South and Central America where abortions are illegal. However, misoprostol is not very effective in inducing abortions, and exposure to the drug in utero can cause abnormalities in the fetus. We aimed to define the common phenotypical effects of exposure to the drug.

Lack of association between antiphospholipid antibodies and first-trimester spontaneous abortion: prospective study of pregnancies detected within 21 days of conception.

Objective: To determine the role of antiphospholipid antibodies and anticardiolipin antibodies in first-trimester losses, addressing experimental pitfalls that preclude excluding the possibility that these antibodies reflect merely the selection bias of studying couples only after they have already experienced losses.

Design: Given that retrospective studies cannot exclude the possibility that such antibodies arise as a result of the fetal death, blood samples were obtained either before pregnancy or very early in pregnancy. Sera were obtained within 21 days of conception.

New syndrome? Prominent, constricted ears with malformed condyle of the mandible.

We report on several relatives in 5 generations of one family with prominence of the ears, with a marked constriction at the junction between the lower and middle thirds of the pinna. Computerized tomography and radiographs in the propositus and his affected father showed abnormalities of the condyle of the mandible. The propositus had more severe changes in the condyle with microstomia and reduced range of motion of the mandible in the temporomandibular joint.

Bob was right.

During his career Bob Brent has been instrumental in developing the methodology to use in determining whether an exposure in pregnancy has a harmful effect on the fetus. Experience has also shown the importance of using this approach to determine when an exposure is not teratogenic. Unfortunately, the attendant debate, as illustrated in two examples reviewed, exogenous sex hormones and Bendectin, requires persistence and a thick skin.

Severe malformation of one foot from amniocentesis needle injury.

An 11-year-old boy is described who was born with a poorly developed right foot. At 16 weeks gestation his mother had had amniocentesis without direct ultrasound guidance. After the insertion of the amniocentesis needle, she felt strong abdominal resistance, which disappeared with slight withdrawal of the needle.

Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome.

Ulnar-mammary syndrome is a rare pleiotropic disorder affecting limb, apocrine gland, tooth and genital development. We demonstrate that mutations in human TBX3, a member of the T-box gene family, cause ulnar-mammary syndrome in two families. Each mutation (a single nucleotide deletion and a splice-site mutation) is predicted to cause haploinsufficiency of TBX3, implying that critical levels of this transcription factor are required for morphogenesis of several organs.