Yuval Gielchinsky

Perinatal outcome of pregnancies complicated by placenta accreta.

OBJECTIVE: The purpose of the study was to characterize the perinatal outcome of pregnancies complicated by placenta accreta. METHODS: We conducted a case-control analysis of all deliveries between the years 1990 and 2000 that were complicated by placenta accreta. Perinatal variables included in the analysis were gestational age at delivery, birth weight, Apgar scores, and perinatal mortality. Statistical analysis was performed using both the unpaired and paired approach. P < .05 was considered significant. RESULTS: The study encompassed 34,450 deliveries, from which 310 cases of placenta accreta were diagnosed (0.9%) and compared with 310 matched controls. In the pregnancies complicated by placenta accreta, we found a statistically significant increase in preterm deliveries (10.7% versus 1%, P < .001, odds ratio 12.1, 95% confidence interval 3.7–39.9) and small-for-gestational-age babies (27.3% versus 14%, P < .001, odds ratio 5.05, 95% confidence interval 1.46–3.28). CONCLUSION: Pregnancies complicated by placenta accreta are at increased risk for perinatal adverse outcome. We speculate that these findings may arise from pathological implantation of the placenta, resulting in interference with normal fetal growth. LEVEL OF EVIDENCE: II-2

Pregnancy restores the regenerative capacity of the aged liver via activation of an mTORC1-controlled hyperplasia/hypertrophy switch

Regenerative capacity is progressively lost with age. Here we show that pregnancy markedly improved liver regeneration in aged mice concomitantly with inducing a switch from proliferation-based liver regeneration to a regenerative process mediated by cell growth. We found that the key mediator of this switch was the Akt/mTORC1 pathway; its inhibition blocked hypertrophy, while increasing proliferation. Moreover, pharmacological activation of this pathway sufficed to induce the hypertrophy module, mimicking pregnancy. This treatment dramatically improved hepatic regenerative capacity and survival of old mice. Thus, cell growth-mediated mass reconstitution, which is relatively resistant to the detrimental effects of aging, is employed in a physiological situation and holds potential as a therapeutic strategy for ameliorating age-related functional deterioration.

Outcomes of subsequent pregnancies after conservative treatment for placenta accreta

To estimate the association between conservative treatment for placenta accreta and subsequent pregnancy outcomes.

Natural conception after age 45 in Bedouin women, a uniquely fertile population

Purpose: Women conceiving naturally and delivering after age 45 are an exceptionally fertile population that may serve as a model to identify factors associated with delayed reproductive aging. This work studies this phenomenon in Bedouin women. Methods: The study is an observational retrospective analysis of all Bedouin women who conceived spontaneously and had their latest delivery after the age of 45 years, during the years 1995–2000 at the participating medical center. Complete histories of the outcomes of all pregnancies were collected. Results: 133 of 34,519 (0.38%) Bedouin women gave birth after the age of 45 years. The mean maternal age at last delivery was 46±1.4 years (range: 45–52), and the mean parity was 11.6±2.9 children (range: 3–18). 96% were grandmultiparous (≥6 deliveries). The mean spontaneous abortion rate (6.6%) was not affected by increased parity and was significantly lower than in the general population: 12.4% vs.17.7% at age 39, 5% vs. 33.8% (p < 0.001) at age 44 and 1.8% vs. 53.2% (p < 0.001) at age 45. Conclusions: This unique group of Bedouin women may have a genetic predisposition to delayed ovarian and oocyte aging.

Gene expression in women conceiving spontaneously over the age of 45 years

OBJECTIVE To examine gene expression profiles of women conceiving spontaneously after the age of 45. DESIGN Expression profiling by complementary DNA microarray analysis. SETTING University departments. PATIENT(S) Eight women 45 years or older (study group) who conceived spontaneously and were 6 months after their last delivery were compared with six women aged 45 years old (control group) who had their last delivery before the age of 30. INTERVENTION(S) Blood samples were collected from each woman for RNA isolation from peripheral blood mononuclear cells (PBMC). MAIN OUTCOME MEASURE(S) Expression profiles of PBMC isolated from each woman were determined by using Affymetrix DNA microarray analysis covering about 15,000 identified genes. RESULT(S) Microarray of global gene expression revealed 671 genes that showed statistically significant differential expression between the study and control groups: 383 genes were overexpressed and 288 were underexpressed. The most significant functional groups defining these genes were: apoptosis, ubiquitination, and energy production. As many as 60 genes also participated in ovarian physiology. CONCLUSION(S) These observations suggest that extended fertility is associated with a unique ability to enrich cellular processes, leading to delayed ovarian senescence.

Rejuvenating effect of pregnancy on the mother

Aging is associated with reduced tissue regenerative capacity. In recent years, studies in mice have shown that transfusion of blood from young animals to old ones can reverse some aging effects and increase regenerative potential similar to that seen in young animals. Because pregnancy is a unique biological model of a partially shared blood system, we have speculated that pregnancy would have a rejuvenating effect on the mother. Recent studies support this idea. In this review, we will summarize the current knowledge of the rejuvenating effect of pregnancy on the mother.

The rejuvenating effect of pregnancy on muscle regeneration

Aging is characterized by reduced tissue regenerative capacity attributed to a diminished responsiveness of tissue‐specific stem cells. With increasing age, resident precursor cells in muscle tissues show a markedly impaired propensity to proliferate in response to damage. However, exposure to factors present in the serum of young mice restores the regenerative capacity of aged precursor cells. As pregnancy represents a unique biological model of a partially shared blood system between young and old organisms, we hypothesized that pregnancy in aged mice would have a rejuvenating effect on the mother. To test this hypothesis, we assessed muscle regeneration in response to injury in young and aged pregnant and nonpregnant mice. Muscle regeneration in the aged pregnant mice was improved relative to that in age‐matched nonpregnant mice. The beneficial effect of pregnancy was transient, lasting up to 2 months after delivery, and appeared to be attributable to activation of satellite cells via the Notch signaling pathway, thus supporting the possibility that pregnancy induces activation of aged dormant muscle progenitor cells.

Induction of labor vs expectant management for suspected fetal macrosomia: a formal decision analysis

PECTED FETAL MACROSOMIA: A FORMAL DECISION ANALYSIS DAVID MANKUTA, YUVAL GIELCHINSKY, MOSHE LESHNO, BREZIS MAYER, Hadassah University Hospital Jerusalem, Obstetrics and Gynecology, Jerusalem, Israel Sackler Faculty of Medicine, Tel-Aviv, Faculty of Management, Tel Aviv, Israel University Hospital Jerusalem, Center for Quality & Safety and School of Public Health, Jerusalem, Israel OBJECTIVE: Themanagement of patients with suspected fetal macrosomia is controversial. Labor induction has been proposed in patients with suspected macrosomia in the late third trimester of pregnancy for prevention of fetal weight gain and its complications during birth. Controlled studies have not shown an advantage compared with ‘‘wait to spontaneous labor’’ approach. We sought to use decision analysis to explore the downstream implications of the labor induction versus no intervention strategy. STUDY DESIGN: We formulated a decision model comparing labor induction vs no intervention approach when fetal macrosomia is suspected. A sensitivity analysis was performed over a variety of probabilities (chances of cesarean section, neurological damage, and truemacrosomia) and utilities (e.g., utility of permanent/temporary neurological damage and/or clavicular fracture, as well as burden and pain associated with labor induction). RESULTS: At base assumptions, the model favors expectant management over induction of labor. Sensitivity analysis showed that this conclusion was robust over a wide range of probabilities and utilities, except for the utility of labor induction. Only if the burden/pain of labor induction would be estimated as negligible, would this option be preferred. Most studies do not consider burden of induction as a factor in the decision. Our analysis suggests that a careful appraisal is needed for the utility of the burden of induction tomother and the caregivers. Individual preferences in this utility by themother or by the staff appear to bemajor determinants in a rational decision. CONCLUSION: Formal decision analysis suggests that the preferred option for suspected macrosomia critically depends on a precise assessment for the burden of labor induction. Expectant management is the preferred option for suspected macrosomia unless the burden of induction is viewed as negligible.