Standardization of amniotic fluid leptin levels and utility in maternal overweight and fetal undergrowth.

OBJECTIVE: Leptin is an adipokine that regulates energy homeostasis. The objective of this study was to establish a gestational age-specific standard for amniotic fluid leptin (AFL) levels and examine the relationship between AFL, maternal overweight and fetal growth restriction. STUDY DESIGN: Amniotic fluid was obtained at mid-gestation from singleton gravidas, and leptin was quantified using enzyme-linked immunosorbent assay. Amniotic fluid samples from 321 term pregnancies were analyzed. Clinical data, including fetal ultrasound measurements and maternal and infant characteristics, were available for a subset of patients (n=45). RESULTS: The median interquartile range AFL level was significantly higher at 14 weeks' gestation (2133 pg ml(-1) (1703 to 4347)) than after 33 weeks' gestation (519 pg ml(-1) (380 to 761), P trend<0.0001), an average difference of 102 pg ml(-1) per week. AFL levels were positively correlated with maternal pre-pregnancy body mass index (BMI) (r=0.36, P=0.03) adjusting for gestational age at measurement, but were not associated with fetal growth. CONCLUSIONS: AFL levels are higher at mid-gestation than at late gestation, and are associated with maternal pre-pregnancy BMI.

Risk of chromosomal abnormalities in patients with idiopathic polyhydramnios.

This prospective investigation was designed to assess the incidence of chromosomal abnormalities in patients with idiopathic polyhydramnios. Polyhydramnios was defined as 25 cm or greater in total vertical height in all four quadrants (amniotic fluid index) in any nonreferral patient (ie, primary care population) undergoing sonographic examination with a singleton pregnancy, normal fetal anatomical survey, normal glucose screening, and negative antibody screen. During the 2-year period from May 1, 1988 through April 30, 1990, 5038 gravidas delivered at Madigan Army Hospital Center. Unexplained polyhydramnios was detected sonographically in 125 patients, an incidence of 2.5%. After obtaining informed written consent, amniocentesis was performed in all patients. Within this group (N = 125), four chromosomal abnormalities (incidence of 3.2%) were detected. There were two trisomy 18 and two trisomy 21 fetuses. None of the four patients had maternal serum alpha-fetoprotein screening performed. The incidence of aneuploidy in patients with idiopathic polyhydramnios (3.2%) is much higher than the reported incidence of major karyotype abnormalities in live births (0.59%). We conclude that fetal chromosomal analysis should be considered in all obstetric patients with sonographic evidence of idiopathic polyhydramnios.

Screening for illicit drug use in a military obstetric population.

The purpose of our investigation was to determine the prevalence of illicit drug use within our socioeconomically heterogeneous obstetric population, in order to assess the need for institution of universal screening. Five hundred consecutive new obstetric registrants had urine collected for routine culture. Following removal of a small aliquot of urine for culture, the samples were sent to the Armed Forces Institute of Pathology, Division of Forensic Toxicology. Each specimen was screened for the presence of alcohol, cocaine metabolites, cannabinoids, opiates, and amphetamines using fluorescent polarization immunoassay techniques. All positive screening tests were confirmed by gas chromatography mass spectrometry. Thirty samples were either lost in processing or of insufficient quantity to test. Five of the 470 samples (1.06%) tested were positive. One subject was taking prescription narcotics, so the correlated prevalence was 0.85%. Three tested positive for tetrahydrocannabinol and two for opiates. Analysis of our data demonstrates that our obstetric population has a significantly lower prevalence of illicit drug use than other populations reported previously (P less than .01). We recommend that each institution providing obstetric services determine its specific prevalence of illicit drug use.

The association of antiphospholipid antibodies with pregnancies complicated by fetal growth restriction.

The association of antiphospholipid antibodies with fetal growth restriction is often cited, but the published evidence for this is based on few patients and comes primarily from patient histories, not study groups. In this prospective study, we evaluated a subgroup of our population with fetuses whose estimated weights at ultrasound were at or below the tenth percentile for gestational age. Plasma and serum testing was performed to determine the presence of antiphospholipid antibodies, specifically lupus anticoagulant and anticardiolipin antibodies, respectively. From March 1990 through March 1991, 55 women were followed for suspected fetal growth restriction. Intensive monitoring of the fetal condition and modification of the mother's activity were recommended, resulting in 100% compliance. Despite this, 37 newborns were confirmed by birth weight to be at or below the tenth percentile, and all were below the 45th percentile. Fifteen of 55 women (27%) were positive for anticardiolipin antibodies, as were nine of 37 (24%) with correctly diagnosed fetal growth restriction. Five of 15 women whose newborns had ponderal indexes below the tenth percentile tested positive for anticardiolipin antibodies. None of the women had a positive lupus anticoagulant test. The prevalence of anticardiolipin antibodies in this study group was significantly higher than in our general population. We conclude that there is a statistically significant association between the presence of circulating maternal anticardiolipin antibodies and fetal growth restriction.

Mechanical factors in the etiology of premature rupture of the membranes.

The physiologic cascade that results in PROM is cyclic and probably can be entered at many points--through the production of collagenases, peroxidases, phospholipases, or prostaglandins. It can be initiated or exacerbated by bacteria. In addition, PROM is the result of direct bacterial insults or host-mediated autodestruction in response to bacterial presence or challenge. It may be affected by physical properties and stresses that are mechanical. This review of the mechanical factors that support normal chorioamnion membranes may provide an understanding of where the support can be eroded, thus leading to PROM. With this basic overview of the pathophysiology contributing to PROM, the clinician can justify clinical decisions better, depending on the patient's presentation and gestational age. The judicious use of various tocolytic agents, antimicrobial agents, and/or corticosteroids singly or in combination is predicated on the effect each of these iatrogenically administered agents will have on the mother and fetus. As more investigations are done, we will gain greater insight into the mechanical factors involved in causing PROM.

The etiology of premature rupture of the membranes.

The etiology of PROM is multifactorial. It is clear that maternal enzymes, maturational and mechanical forces, chorionicamniotic membrane phospholipid content, collagen disruption, amniotic cell cytokines induced by fetal signals, and bacterial phospholipases and collagenases all play major and interrelated roles. It is also clear that the production of oxytocic prostaglandins is a major, if not exclusive, common pathway leading to PROM and preterm delivery. The increasing awareness of the fetal role, i.e., fetal interleukins, fetal polymorphonuclear leukocytes and type V collagenase, make this area of research ripe for further investigation. The complex host defense mechanisms and biologic variability make any universal treatment impossible. Even with a specific etiology determined, the reduced availability of pharmacologic interventions for the fetal compartment portend suboptimal success. Therefore, it appears that continued research and aggressive measures to optimize the quality and availability of prenatal care are the best foci of our efforts.

Fetal choroid plexus cysts in association with cri du chat (5p-) syndrome.

The significance of fetal choroid plexus cysts is controversial. We report a case of antenatally detected cri du chat syndrome (5p-) in one fetus of a twin pregnancy in association with bilateral fetal choroid plexus cysts and unassociated with other structural malformations. Choroid plexus cysts may be nonspecific markers for chromosomal anomalies.

A pilot study identifying type V collagenolytic activity in human amniotic fluid.

Amniorrhexis complicates pregnancies if it occurs in a preterm pregnancy or remote from the onset of labor in a term pregnancy. There are different collagen types (I-V) that create the extracellular matrix of the amnion. Collagenases specific to these collagen types, with the exception of type V collagen, are found in human amniotic fluid, fibroblasts, polymorphonuclear leukocytes and bacteria. Type V collagen is a major component of the amniotic basement membrane and is responsible for maintaining a barrier to bacteria and to the loss of amniotic fluid. We sought to find evidence of type V collagenolytic activity in human amniotic fluid obtained from pregnancies in different clinical states.

Transabdominal amnioinfusion in preterm pregnancies complicated by fetal growth restriction, oligohydramnios and umbilical cord compression.

Fetal growth restriction with oligohydramnios occurring in the preterm gestation is associated with significant fetal morbidity and mortality. We investigated the possibility that transabdominal amnioinfusion might relieve acute cord compression and allow prolongation of gestation long enough to administer corticosteroids. Four patients with fetal growth restriction, oligohydramnios and evidence of significant cord compression with otherwise reassuring fetal heart rate testing underwent transabdominal amnioinfusion. Pregnancy was prolonged 22, 38, 10 and 9 days, and cord compression was relieved in all cases. One patient showed findings consistent with reversal of chronic hypoxemia with stabilization of amniotic fluid index measurements in the normal range and normalization of fetal growth. Transabdominal amnioinfusion may be useful as an adjunctive technique to prolong pregnancy in preterm gestations with fetal growth restriction, oligohydramnios and evidence of umbilical cord compression.