Issues in implementing prenatal screening for cystic fibrosis: results of a working conference.

PURPOSE: To summarize a conference convened to examine how cystic fibrosis screening might appropriately be introduced into routine prenatal practice. METHODS: Participants included experts from various relevant disciplines. Systematic reviews and data from individual trials were presented; issues were identified and discussed. RESULTS: Judged by published criteria, prenatal cystic fibrosis screening is suitable for introduction. Screening can be performed cost-effectively by identifying racial/ethnic groups at sufficient risk and then using either of two models for delivering laboratory services. Validated educational materials exist. Ethical issues are not unique. CONCLUSIONS: Once adequate facilities for patient and provider education, testing, counseling, quality control, and monitoring are in place, individual programs can begin prenatal screening for cystic fibrosis.

Massive chronic intervillositis associated with recurrent abortions.

Massive chronic intervillositis (MCI) is an unusual placental lesion associated with poor fetal growth and adverse pregnancy outcome; it has not previously been associated with spontaneous abortion or recurrent pregnancy loss. This article reports a patient who had 10 spontaneous abortions with repetitious massive chronic intervillositis documented in four of five gestations spanning all three trimesters. Characteristic placental histology induced massive infiltration of the maternal intervillous space by chronic inflammatory cells and fibrin, without associated chronic villitis; the cellular infiltrate was composed predominantly of LCA and CD68 immunoreactive cells with scattered CD45RO positivity, consistent with a monocyte/macrophage population with occasional T lymphocytes. Elevated maternal serum alpha-fetoprotein was documented in two pregnancies. These findings support the concept that this unusual placental lesion may have an immunologic basis, and suggest that MCI may be a histopathologically recognizable cause of recurrent spontaneous abortion.

Animal models for perinatal transmission of pathogenic viruses.

In earlier work, mouse models have been used to demonstrate the efficacy and lack of toxicity of transplacental and perinatal AZT therapy. These practical small animal models can be useful for evaluating antiviral drugs aimed at common retroviral functions only, since Type C MuLVs are used. A primate model for fetal infection with an immunosuppressive lentivirus, SIV, has been established using ultrasound-guided inoculation of the amniotic fluid. The infection rate was 86% overall and 100% if the fetal SIV exposure occurred at least 19 days before delivery. The suspected major route of vertical HIV-1 transmission, that is, virus entry through fetal mucous membranes or skin, is replicated by our approach. The high fetal infection rate will allow studies of SIV pathogenesis during various stages of fetal development. This model should be well suited to development and evaluation of therapeutic strategies for preventing fetal infection.

Simian immunodeficiency virus infection via amniotic fluid: a model to study fetal immunopathogenesis and prophylaxis.

The rising prevalence of infection with the human immunodeficiency virus type 1 (HIV-1) in young women will increase the number of infected children worldwide. Because HIV-1 seems to be transmitted mostly intrapartum, fetal infection probably occurs mainly via skin or mucous membrane exposure. A model for this route of fetal infection has been established in primates. After injecting the simian immunodeficiency virus (SIV) into amniotic fluid during late gestation, six of seven rhesus monkeys were born infected. All infected neonates were viable and showed signs of disease, such as low birth weights, lymphadenopathy, and rashes. Cytotoxic T-cell responses to SIV were absent in neonates, but present in mothers. The high fetal infection rate allows studies of lentiviral immunopathogenesis during ontogeny and the development of strategies to prevent maternal HIV-1 transmission.

Renal dysplasia, megalocystis, and sirenomelia in four siblings.

First degree relatives of infants with bilateral renal agenesis or dysplasia have an increased risk of renal abnormalities including renal agenesis. We report a family in which four successive offspring exhibited a previously undescribed combination of congenital lethal renal disorders: bilateral renal dysplasia, megalocystis secondary to urethral obstruction and, sirenomelia with associated renal agenesis.

The prenatal sonographic features of Noonan's syndrome.

The sonographic findings in four infants with Noonan's syndrome are described. All four fetuses had cystic hygromata located laterally along the cervical spine and normal karyotypes. Three of the four pregnancies were complicated by polyhydramnios and those three fetuses had associated pleural effusions. One fetus developed frank hydrops and did not survive, a clinical course that appears to be part of the clinical spectrum of Noonan's syndrome. The diagnosis of Noonan's syndrome was given serious consideration prenatally based on the sonographic findings and normal karyotype and confirmed at birth in all four cases. Three of the infants survived.

Fetal surgery and general anesthesia: a case report and review.

Fetal surgery, in utero, is now a viable option for some congenital conditions due to recent advances in ultrasound and microsurgical technology. Previous reports of anesthesia for such procedures have focused on spinal or epidural conduction techniques. General endotracheal anesthesia may have several advantages in this setting. In addition to maternal anesthesia, general anesthesia can provide fetal neuromuscular block (without direct fetal injection of blocking agents) and uterine relaxation. It may also blunt fetal response to surgical stimulation.

Insulin stimulates cord blood erythroid progenitor growth: evidence for an aetiological role in neonatal polycythaemia.

Polycythaemia in the neonate is a serious pathologic entity which occurs particularly in infants of diabetic mothers (IDM) and small-for-gestational age (SGA) infants. Both of these conditions are associated with fetal hyperinsulinaemia. Cultures of cord blood mononuclear cells from polycythaemic IDM showed increased growth of late erythroid progenitor colonies, compared to cord blood mononuclear cells from non-polycythaemic infants, reflecting a possible expansion of this progenitor population in the polycythaemic fetus. No changes were observed in early erythroid progenitor populations. Biosynthetic human insulin at physiological levels characteristic of IDM stimulated growth in culture of late erythroid progenitors in cord blood from premature, term and IDM infants. Three out of five polycythaemic infants had elevated cord blood plasma levels of insulin C-peptide at birth, whereas no infant with a haematocrit of less than 65% had high insulin C-peptide measurements. These data suggest that the polycythaemia noted in infants of diabetic mothers may be secondary, in large part, to a stimulatory effect on erythroid progenitor growth by the hyperinsulinaemic environment in which they develop in utero.

Prenatal sonographic diagnosis of congenital hemivertebra.

The prenatal sonographic diagnosis of spinal abnormalities associated with neural tube element malformations has been well described; however, the diagnosis of fetal skeletal anomalies of the vertebral bodies with a neurologically intact spine has received little attention. Three cases of congenital hemivertebra should alert the sonographer to search for other congenital defects and for orthopedic complications of vertebral body malformations in childhood. Prior knowledge of the presence of an abnormal vertebral body can alert the pediatrician to watch for early signs of problems such as scoliosis or kyphoscoliosis, and to plan surgery if necessary.

Complexities of intraventricular abnormalities.

We identified 59 fetuses and infants with intracranial anomalies over 5 1/2 years. The cases represented heterogeneous diagnostic groups: hydrocephalus with a neural tube defect, hydrocephalus with a specified structural anomaly, hydrocephalus of unspecified or miscellaneous cause, holoprosencephaly, and hydranencephaly. One or more major nonneural tube malformations were present in 19 of 54 cases. Eight of 32 cases had a significant chromosomal abnormality. The rate of survival was poor: 13 of 59 pregnancies were terminated electively before 24 weeks gestation, 10 of 59 infants were stillborn, and 16 of the remaining 38 liveborn infants have died since birth. A prenatal ultrasonographic diagnosis was made in the majority of cases (50 of 59). Diagnostic accuracy of prenatal ultrasound examinations ranged from a high of 90% for hydrocephalus to 33% for holoprosencephaly and hydranencephaly, and a low of 22% for the presence of extracranial malformations. Eleven cases in this series could have been considered potential candidates for in utero treatment of ventriculomegaly; this therapy would have been ineffective or inappropriate in eight of these. We recommend that each case undergo thorough diagnostic evaluation, including ultrasound examination and chromosome studies; that parents be informed of the high frequency of associated anomalies, the poor prognosis regarding survival, and the current limitations of ultrasound diagnostic accuracy; and that in utero treatment of fetal ventriculomegaly seems inadvisable at the present time.

Pregnancy complicated by homozygous hypercholesterolemia.

The course of pregnancy in a woman with homozygous type IIa hypercholesterolemia is described. Despite prepartum cholesterol levels as high as 700 mg/dL, her cholesterol level increased further during gestation. Pathological examination of the placenta did not reveal insufficiency or vasculopathy.