Amelia C. Cruz

Expression Profile of MicroRNAs and mRNAs in Human Placentas From Pregnancies Complicated by Preeclampsia and Preterm Labor

MicroRNAs (miRNAs) have emerged as key regulators of gene expression stability implicated in cell proliferation, apoptosis, and development, whereas their altered expression has been associated with various pathological disorders. The objective of this study was to assess the expression profile of miRNAs and their predicted target genes in placentas from patients with preeclampsia (PC) and preterm (PT) labor as compared to normal term (NT) pregnancies. Using microarray profiling of 820 miRNAs and 18,630 mRNA transcripts, the analysis indicated that 283 of these miRNAs and 9119 mRNAs were expressed in all placentas, of which the relative expression of 20 miRNAs (P < .05 and ≥1.5-fold) and 120 mRNAs (P < .05, and 2-fold cutoff) was differentially expressed in PT and PC as compared to NT. The expression of miR-15b, miR-181a, miR-200C, miR-210, miR-296–3p, miR-377, miR-483–5p, and miR-493 and a few of their predicted target genes: matrix metalloproteinases (MMP-1, MMP-9), a disintegrin and metalloproteinase domains (ADAM-17, ADAM-30), tissue inhibitor of metalloproteinase 3 (TIMP-3); suppressor of cytokine signaling 1 (SOCS1); Stanniocalcin (STC2); corticotropin-releasing hormone (CRH), CRH-binding protein (CRHBP); and endothelin-2 (EDN2) were validated in these cohorts using real-time polymerase chain reaction (PCR), some displaying an inverse correlation with the expression of their predicted target genes. Functional analysis indicated that the products of these genes regulate cellular activities considered critical in normal placental functions and those affected by PC and PT labor. In conclusion, the results provide further evidence that placentas affected by PC and PT labor display an altered expression of a number of miRNAs with potential regulatory functions on the expression of specific target genes whose altered expression and function have been associated with these pregnancy complications.

Psychological response to prenatal genetic counseling and amniocentesis.

The purpose of the present study was to characterize the psychological status (attitudes toward selective abortion, perceived risk, comprehension, patient satisfaction, coping, and state anxiety) of pregnant women at increased risk for fetal genetic anomalies who were referred for prenatal genetic counseling and amniocentesis; to determine which of these factors would predict amniocentesis use; and to identify patient outcomes associated with counseling and testing. Participants were 129 women aged 18 years and older who had one or more fetal genetic risk factors. All were recruited from an urban womens health clinic. The results revealed elevated perceptions of risk and moderate state anxiety despite adequate comprehension of, and patient satisfaction with, the process and content of genetic counseling. Approximately 78% agreed to testing; those who consented were more likely to hold favorable attitudes toward abortion than those who refused. Post-counseling, women experienced decrease in their perceived risk of having a baby born with a birth defect although perceived risk estimates remained higher than actual risks. Anxiety was clinically elevated and highest at the pre-counseling stage, though it dissipated to normal levels over time. Previous experience with prenatal diagnostic testing, increased perceived risk of a birth anomaly, and favorable attitudes toward abortion were independently associated with increased pre-counseling anxiety. Women who were more anxious pre-counseling remained more anxious post-counseling. Coping (high versus low monitoring) was unrelated to anxiety. These findings suggest that women who participate in prenatal counseling and testing may be subject to experience distress and unrealistic perceptions of their risk and may benefit from interventions designed to lessen these states.

Respiratory distress syndrome with mature lecithin/sphingomyelin ratios: Diabetes mellitus and low Apgar scores

A detailed study was made of 150 women delivered of their infants within 72 hours of an amniocentesis where the lecithin/sphingomyelin (L/S) ratio was 2.0 or greater. There were nine neonates with respiratory distress (6.0 per cent). There were two neonatal deaths, both due to severe congenital heart disease. A mature amniotic fluid L/S ratio predicts a newborn infant who will not have respiratory distress syndrome (RDS) in most pregnancies. There is a significantly increased risk of RDS in neonates with a mature L/S ratio if the mother has insulin-dependent diabetes or if there is a resulting low Apgar score. The method of delivery (cesarean section or vaginal) does not affect the frequency of RDS where the L/S ratio is 2.0 or more.

The acute effects of ritodrine infusion on maternal metabolism: Measurements of levels of glucose, insulin, glucagon, triglycerides, cholesterol, placental lactogen, and chorionic gonadotropin

Twenty-nine women in premature labor were randomly assigned to a ritodrine (N = 14) or placebo (N = 15) treatment group. Thirteen serial blood samples were drawn during the first 12 hours of therapy by intravenous drug infusion and they were analyzed for a variety of metabolic substances. There was a significant increase in the blood glucose level in the ritodrine group after one hour and this persisted for the 12 hours of intravenous drug treatment. Plasma insulin levels similarly did not increase in the placebo but significantly rose in the ritodrine group by 30 minutes, peaked at 2 1/2 hours, and remained elevated throughout the infusion. There were no significant differences between levels of plasma glucagon, cholesterol triglyceride, human placental lactogen, or human chorionic gonadotropin in the two treatment groups. Ritodrine caused significant maternal and fetal tachycardia. Its use in women with carbohydrate abnormalities should be monitored carefully. The increased glucose levels may lead to an increased fetal weight.

Maternal weight gain: Effect on infant birth weight among overweight and average-weight low-income women

A study was performed to compare the influence of pregnancy weight gain on infant birth weight and outcome among two groups of indigent women from the rural South: those who were highly overweight before pregnancy (greater than or equal to 135%) and those who were of average weight (90% to 120% of standard weight for height). The groups had comparable numbers of black and white subjects. Pregnancy weight gain affected birth weight in the average-weight group but did not significantly affect birth weight in the highly overweight group. Infant outcomes for both groups were similar. These findings suggest that consideration should be given to not requiring a minimum weight gain for women whose degree of overweight equals or exceeds 135% of standard body weight for height.

Changes in placental ultrasonic appearance

Placental grading has been proposed as a substitute for amniotic fluid analysis for predicting fetal pulmonary maturity. The efficacy of placental grading was prospectively evaluated by grading the placenta at the time of 174 amniocentesis procedures done for determination of fetal pulmonary maturity. Grade III changes in the placenta were a rare finding that occurred in only 7% of the examinations performed. Placental grading proved to be insensitive in that it predicted pulmonary maturity in only 5% of pregnancies in which amniotic fluid analysis predicted a mature fetus. In addition, placental grading falsely predicted fetal pulmonary maturity in 42% of patients in whom Grade III placental changes were found. These findings suggest that the determination of Grade III changes in the placenta occurs too rarely to be of use in predicting fetal pulmonary maturity in the uncomplicated pregnancy. Incorrect prediction of pulmonary maturity by placental grading in the complicated pregnancy makes this test of little value in the management of high-risk pregnancy.

Ultrasonographic diagnosis of congenital anomalies in twins

To determine whether serial ultrasonographic examinations with basic anatomic surveys provide an adequate screen for congenital abnormalities that are more common in twins, we compared the results of prenatal sonograms and neonatal examinations for 314 twins (157 pairs) delivered during a recent 42-month period. An anomaly was defined as major if it potentially required surgical repair or precluded normal life expectancy; otherwise it was defined as minor. Thirty-three twins (9.5%) had 40 anomalies; 28 (9%) were major and 12 (4%) were minor. Prenatal ultrasonography with cardiac screening limited to the four-chamber view provided detection of 39% of all major anomalies, 55% of noncardiac major anomalies but none of the cardiac lesions, and 69% of the major anomalies for which routine prenatal management should be altered. No false-positive diagnoses incorrectly altered management. We conclude that serial prenatal ultrasonographic examinations are useful in detecting noncardiac anomalies for which twins are at increased risk, but the four-chamber view is not an adequate screen for the cardiac malformations of twins.

Hydramnios: ultrasound diagnosis and its impact on perinatal management and pregnancy outcome.

Ultrasonographic technique allows for noninvasive quantification of amniotic fluid volume in pregnancy. A series of 12 pregnancies with ultrasonographically confirmed hydramnios is presented in detail. Following the diagnosis of hydramnios an intensive system-by-system evaluation of the fetal structures was performed. Developmental defects known to be associated with the production of hydramnios were detected in 83% of these pregnancies. Anomalies detected included abdominal wall defects, abnormalities of the central nervous system, pleural effusions, obstructions of the fetal gastrointestinal tract, and others. The early definition of hydramnios and the subsequent discovery of anomalies associated with increased amniotic fluid volume may lead to alteration in prenatal care, in intrapartum management, and in postdelivery resuscitative measures in these complicated pregnancies. In this series, despite early diagnosis of hydramnios and associated fetal developmental anomalies, complications of the pregnancies directly resultant from hydramnios resulted in a high perinatal mortality rate.

Changes in placental ultrasonic appearance. II. Pathologic significance of Grade III placental changes.

Changes in placental texture and structure on ultrasonic examination have been suggested as correlating to advancing fetal pulmonary maturity. The association of preterm appearance of Grade III changes in the placenta in the complicated pregnancy suggests that these changes are associated with a decrease in placental function and premature senescence of the placenta. Placentas were routinely graded on all obstetric examinations performed during a 1-year period of time. Those pregnancies in which Grade III changes in the placenta prior to term were reviewed. A high incidence (78%) of perinatal problems were found in association with preterm appearance of Grade III changes. Perinatal complications included maternal hypertensive disorders, intrauterine growth retardation, abruptio placentae, and fetal distress in labor. The high incidence of these disorders in preterm pregnancies with Grade III changes in the placenta suggests that the sonographic changes found reflect placental dysfunction or senescence rather than normal maturational development. The appearance of Grade III changes in the placenta in the preterm pregnancy is suggested as a predictive indicator of potential perinatal problems in late pregnancy.

Persistent placenta increta: A complication of conservative management of presumed placenta accreta

Background Recent reports have advocated conservative management rather than hysterectomy for placenta increta and its related conditions, placenta accreta and percreta. We report an unusual case of placenta increta in which initial conservative therapy for a presumed placenta accreta failed and hysterectomy was performed 6 months postpartum. Case A 32-year-old woman, gravida 2, para 2, was referred 5 months after a repeat cesarean delivery and bilateral tubal interruption for evaluation of an intrauterine mass. A presumed placenta accreta noted at delivery had been managed conservatively. Hysterectomy was performed, and pathologic evaluation was consistent with a retained placenta increta. Conclusion Persistent placental tissue is a potential complication of conservative management of an abnormally adherent placenta.