Early onset preeclampsia and cerebral palsy: a double hit model?

BACKGROUND: Cerebral palsy (CP) is a late sequel of pregnancy, and the role of preeclampsia is debatable. OBJECTIVE: The aims of this study were to determine the association between preeclampsia and cerebral palsy and to determine the risk factors for the development of cerebral palsy in these patients. STUDY DESIGN: A retrospective population-based cohort study was designed that included 229,192 singleton pregnancies. The study population was divided into 2 groups: (1) patients with preeclampsia (n = 9749) and (2) normotensive gestations (n = 219,443). Generalized Estimating Equation multiple logistic regression models were performed to study the associations among preeclampsia, small for gestational age, gestational age at delivery, and the risk factors for the development of cerebral palsy in neonates of women with preeclampsia. RESULTS: The rate of cerebral palsy was double in patients with preeclampsia than in the normotensive group (0.2% vs 0.1%; P = .015); early onset preeclampsia and small for gestational age were independent risk factors for the subsequent development of cerebral palsy (odds ratio, 8.639 [95% confidence interval, 4.269-17.480]; odds ratio, 2.737 [95% confidence interval, 1.937-3.868], respectively). A second model was conducted to determine the risk factors for the development of cerebral palsy in women with preeclampsia. Birth asphyxia, complications of prematurity, and neonatal infectious morbidity, but not small for gestational age or gestational age at delivery, were independent risk factors for the development of cerebral palsy. CONCLUSION: In a comparison with normal pregnant women, the rate of cerebral palsy is double among patients with preeclampsia, especially those with early-onset disease. Early-onset preeclampsia is an independent risk factor for cerebral palsy. Among women with preeclampsia, the presence of neonatal infectious morbidity, birth asphyxia, and complications of prematurity are independent risk factors for the development of cerebral palsy, which further supports the role of a multi-hit model in the pathogenesis of this syndrome.

The use of imaging technology in the assessment of the fetal inflammatory response syndrome-imaging of the fetal thymus.

The fetal inflammatory response syndrome (FIRS) describes a state of extensive fetal multi organ involvement during chorioamnionitis, and is associated with grave implications on perinatal outcome. The syndrome has been linked to the preterm parturition syndrome and is associated with inflammation/infection processes in most of the fetal organs. The fetal thymus, a major organ in the developing immune system involutes during severe neonatal disease and has been shown to be smaller in fetuses with FIRS. Various methods for imaging of the fetal thymus and measurement are described. Currently the only method to diagnose FIRS prenatally is through amniocentesis. We suggest that women who are admitted with preterm labor with intact membranes and those with PPROM should have a detailed sonographic examination of the fetal thymus as a surrogate marker of fetal involvement in intrauterine infection/inflammation processes.

The effect of non-obstetric invasive procedures during pregnancy on perinatal outcomes.

PURPOSE: To evaluate the effect of non-obstetric invasive procedure during pregnancy on perinatal outcome. METHODS: The present retrospective study investigated perinatal outcome in women that underwent an invasive procedure during one of their pregnancies (n = 61); perinatal outcome was compared to other pregnancies (without an invasive procedure) of the same patients (n = 122). RESULTS: Women with a non-obstetric invasive procedure during pregnancy delivered earlier than those in the comparison group (38.5 vs. 40.0 weeks; p = 0.01) and had a significantly higher rate of cesarean sections (18 vs. 5 cases; p < 0.01). In addition, birth weight was significantly lower in patients undergoing invasive procedures during pregnancy (2908.65 vs. 3185.84 gr; p = 0.02). The absolute rate of prematurity (<37 weeks) was non-significantly higher in the study group (18.3 vs. 10.0 %; p = 0.28). CONCLUSION: Non-obstetric invasive procedures are associated with an increased rate of cesarean sections and lower birth weight. Nevertheless, no significant differences in early perinatal outcome were found in comparison to other pregnancies of the same patients. More studies are needed to evaluate the outcome following specific procedures.

Pregnancy complicated by obesity induces global transcript expression alterations in visceral and subcutaneous fat.

Maternal obesity is a significant risk factor for development of both maternal and fetal metabolic complications. Increase in visceral fat and insulin resistance is a metabolic hallmark of pregnancy, yet not much is known how obesity alters adipose cellular function and how this may contribute to pregnancy morbidities. We sought to identify alterations in genome-wide transcription expression in both visceral (omental) and abdominal subcutaneous fat deposits in pregnancy complicated by obesity. Visceral and abdominal subcutaneous fat deposits were collected from normal weight and obese pregnant women (n = 4/group) at the time of scheduled uncomplicated cesarean section. A genome-wide expression array (Affymetrix Human Exon 1.0 st platform), validated by quantitative real-time PCR, was utilized to establish the gene transcript expression profile in both visceral and abdominal subcutaneous fat in normal weight and obese pregnant women. Global alteration in gene expression was identified in pregnancy complicated by obesity. These regions of variations led to identification of indolethylamine N-methyltransferase, tissue factor pathway inhibitor-2, and ephrin type-B receptor 6, not previously associated with fat metabolism during pregnancy. In addition, subcutaneous fat of obese pregnant women demonstrated increased coding protein transcripts associated with apoptosis as compared to lean counterparts. Global alteration of gene expression in adipose tissue may contribute to adverse pregnancy outcomes associated with obesity.

The peripheral whole-blood transcriptome of acute pyelonephritis in human pregnancya.

OBJECTIVE: Human pregnancy is characterized by activation of the innate immune response and suppression of adaptive immunity. The former is thought to provide protection against infection for the mother, and the latter, tolerance against paternal antigens expressed in fetal cells. Acute pyelonephritis is associated with an increased risk of acute respiratory distress syndrome and sepsis in pregnant (vs. nonpregnant) women. The objective of this study was to describe the gene expression profile (transcriptome) of maternal whole blood in acute pyelonephritis. METHOD: A case-control study was conducted to include pregnant women with acute pyelonephritis (n=15) and women with a normal pregnancy (n=34). Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix, Santa Clara, CA, USA) were used for gene expression profiling. A linear model was used to test the association between the presence of pyelonephritis and gene expression levels while controlling for white blood cell count and gestational age. A fold change of 1.5 was considered significant at a false discovery rate of 0.1. A subset of differentially expressed genes (n=56) was tested with real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (cases, n=19; controls, n=59). Gene ontology and pathway analyses were applied. RESULTS: A total of 983 genes were differentially expressed in acute pyelonephritis: 457 were upregulated and 526 were downregulated. Significant enrichment of 300 biological processes and 63 molecular functions was found in pyelonephritis. Significantly impacted pathways in pyelonephritis included (a) cytokine-cytokine receptor interaction, (b) T-cell receptor signaling, (c) Jak-STAT signaling, and (d) complement and coagulation cascades. Of 56 genes tested by qRT-PCR, 48 (85.7%) had confirmation of differential expression. CONCLUSION: This is the first study of the transcriptomic signature of whole blood in pregnant women with acute pyelonephritis. Acute infection during pregnancy is associated with the increased expression of genes involved in innate immunity and the decreased expression of genes involved in lymphocyte function.

Third-trimester abnormal uterine artery Doppler findings are associated with adverse pregnancy outcomes.

OBJECTIVES: To evaluate the association between third-trimester abnormal uterine artery Doppler findings and pregnancy outcomes. METHODS: A prospective study was designed, including 198 consecutive singleton pregnancies between 27 and 41 weeks' gestation. In the study population, 144 had normal uterine artery Doppler waveforms, 37 had unilateral pathologic waveforms, and 17 had bilateral pathologic waveforms. Eighty patients had intrauterine growth restriction (IUGR), preeclampsia toxemia, or both, and 118 had no complications and served as a control group. The uterine artery Doppler waveform was considered abnormal when a notch or pulsatility index above the 90th percentile was noted. RESULTS: In patients with bilateral pathologic uterine artery Doppler waveforms, the rates of cesarean delivery, small-for-gestational-age (SGA) neonates, preterm delivery, and low Apgar scores were increased compared to patients with normal or pathologic unilateral waveforms (P = .009; P > .001; P = .007; P > .001, respectively). The incidence rates for SGA neonates, cesarean delivery, and preterm delivery were significantly higher among patients without IUGR or preeclampsia toxemia when associated with pathologic bilateral waveforms in comparison to normal waveforms (P = .01 for all). A bilateral pathologic waveform was found to be an independent risk factor for cesarean delivery and SGA neonates. The incidence rates for SGA neonates and preterm delivery were significantly higher among patients with IUGR and/or preeclampsia toxemia when associated with bilateral abnormalities in comparison to normal waveforms (P = .01 for both). CONCLUSIONS: Third-trimester abnormal uterine artery Doppler findings are associated with worse perinatal outcomes among patients both with and without pregnancy complications.

Induction of labor after a prior cesarean delivery: lessons from a population-based study.

OBJECTIVES: The aims of this study were (1) to determine the success rate of induction of labor (IOL) in women with a prior cesarean section (CS) and (2) to compare the perinatal outcome of a trial of labor (TOL) in women with one prior CS who had an IOL, spontaneous onset of labor, or an elective repeated CS (ERCS). MATERIAL AND METHODS: This study population was divided into three groups: women who had (1) ERCS (n = 1916), (2) spontaneous TOL (n = 4263), and (3) IOL (n = 1576). RESULTS: (1) The rate of IOL in the study cohort was 20.3%; of these, 67.4% had a successful vaginal birth after cesarean (VBAC). (2) Patients in the spontaneous TOL group had a higher VBAC rate than did those who had IOL (P < 0.001). (3) The rate of uterine rupture was comparable among all study groups. And (4) a prior vaginal birth increased the likelihood of having a successful induction and a VBAC by 50%. CONCLUSION: IOL in patients with a previous CS is successful in about two-thirds of the cases. Induction is a safe and useful tool that can serve as an alternative for ERCS and assist to reduce the rate of ERCS.

Characterization of the myometrial transcriptome in women with an arrest of dilatation during labor.

OBJECTIVE: The molecular basis of failure to progress in labor is poorly understood. This study was undertaken to characterize the myometrial transcriptome of patients with an arrest of dilatation (AODIL). STUDY DESIGN: Human myometrium was prospectively collected from women in the following groups: (1) spontaneous term labor (TL; n=29) and (2) arrest of dilatation (AODIL; n=14). Gene expression was characterized using Illumina® HumanHT-12 microarrays. A moderated Student's t-test and false discovery rate adjustment were used for analysis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) of selected genes was performed in an independent sample set. Pathway analysis was performed on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database using Pathway Analysis with Down-weighting of Overlapping Genes (PADOG). The MetaCore knowledge base was also searched for pathway analysis. RESULTS: (1) Forty-two differentially expressed genes were identified in women with an AODIL; (2) gene ontology analysis indicated enrichment of biological processes, which included regulation of angiogenesis, response to hypoxia, inflammatory response, and chemokine-mediated signaling pathway. Enriched molecular functions included transcription repressor activity, heat shock protein (Hsp) 90 binding, and nitric oxide synthase (NOS) activity; (3) MetaCore analysis identified immune response chemokine (C-C motif) ligand 2 (CCL2) signaling, muscle contraction regulation of endothelial nitric oxide synthase (eNOS) activity in endothelial cells, and triiodothyronine and thyroxine signaling as significantly overrepresented (false discovery rate <0.05); (4) qRT-PCR confirmed the overexpression of Nitric oxide synthase 3 (NOS3); hypoxic ischemic factor 1A (HIF1A); Chemokine (C-C motif) ligand 2 (CCL2); angiopoietin-like 4 (ANGPTL4); ADAM metallopeptidase with thrombospondin type 1, motif 9 (ADAMTS9); G protein-coupled receptor 4 (GPR4); metallothionein 1A (MT1A); MT2A; and selectin E (SELE) in an AODIL. CONCLUSION: The myometrium of women with AODIL has a stereotypic transcriptome profile. This disorder has been associated with a pattern of gene expression involved in muscle contraction, an inflammatory response, and hypoxia. This is the first comprehensive and unbiased examination of the molecular basis of an AODIL.

Do patients who deliver at term after being hospitalized for preterm contractions have an increased risk for obstetrical complications?

OBJECTIVES: To determine the obstetrical complications and perinatal outcomes of patients with recurrent episodes of preterm contractions (PTC) that eventually delivered at term compared to those who delivered preterm. METHODS: A retrospective study evaluating pregnancy complications and adverse perinatal outcomes of patients with recurrent episodes of PTC (three or more) was conducted. A comparison was made between those who delivered preterm to those who eventually delivered at term. RESULTS: Deliveries occurred between the years 1989 and 2009. During the study period, there were 1,897 singleton deliveries at term and 393 preterm singleton deliveries of patients who were previously hospitalized with PTCs. Patients who delivered at term were significantly more likely to be in their first pregnancy and to be primiparous. Patients in the study group were less likely to have had fertility treatments, a history of miscarriage, a higher incidence of one previous hospitalization but lower rates of multiple hospitalizations for PTC. Patients who delivered at term had a significantly lower rate of severe preeclampsia as well as cesarean delivery and a shorter hospital stay than those who delivered preterm. At term, an increased incidence of small for gestational age (SGA) neonates was noted compared to patients who delivered prematurely (10.07 vs. 5.6 %; P = 0.005). CONCLUSION: Patients with symptoms of preterm labor may require further surveillance, not only because of their risk to progress to preterm delivery, but also because they are at an increased risk for delivering an SGA neonate at term.

Early preterm delivery due to placenta previa is an independent risk factor for a subsequent spontaneous preterm birth.

BACKGROUND: To determine whether patients with placenta previa who delivered preterm have an increased risk for recurrent spontaneous preterm birth. METHODS: This retrospective population based cohort study included patients who delivered after a primary cesarean section (n = 9983). The rate of placenta previa, its recurrence, and the risk for recurrent preterm birth were determined. RESULTS: Patients who had a placenta previa at the primary CS pregnancy had an increased risk for its recurrence [crude OR of 2.65 (95% CI 1.3-5.5)]. The rate of preterm birth in patients with placenta previa in the primary CS pregnancy was 55.9%; and these patients had a higher rate of recurrent preterm delivery than the rest of the study population (p < .001). Among patients with placenta previa in the primary CS pregnancy, those who delivered preterm had a higher rate of recurrent spontaneous preterm birth regardless of the location of their placenta in the subsequent delivery [OR 3.09 (95% CI 2.1-4.6)]. In comparison to all patients with who had a primary cesarean section, patients who had placenta previa and delivered preterm had an independent increased risk for recurrent preterm birth [OR of 3.6 (95% CI 1.5-8.5)]. CONCLUSIONS: Women with placenta previa, who deliver preterm, especially before 34 weeks of gestation, are at increased risk for recurrent spontaneous preterm birth regardless to the site of placental implantation in the subsequent pregnancy. Thus, strict follow up by high risk pregnancies specialist is recommended.

Anxiety and deterioration of quality of life factors associated with recurrent miscarriage in an observational study.

OBJECTIVES: To examine the relationship of anxiety and quality of life and sleep variables to recurrent miscarriages (RMs) in patients during two stages of their treatment in an RM-dedicated clinic ­ before and after the evaluation ­ and determine what factors could aggravate anxiety and worsen global well-being outcomes. STUDY DESIGN: Thirty-nine women who had experienced two or more RMs were measured before and after their evaluation and investigation in the RM clinic. A battery of questionnaires including the STAI scale and various instruments were administered to record anxiety, mental, and physical components of quality of life and sleep quality. Several statistical tests including canonical correlation were performed. RESULTS: All the patients revealed a mild to moderate level of anxiety, low numbers of physical and mental health but reasonably normal values of the global quality of sleep. The evaluation in the RM clinic and investigation for possible causes accounting for RM did not significantly change anxiety levels. The children-to-pregnancies ratio introduced into the analysis proved to correlate significantly with the sleep quality and mental health. Summarized anxiety in a given RM woman could be predicted based on the set of the variables, characterizing the woman's reproductive status and her psychological health. CONCLUSIONS: This study establishes anxiety as a common response in RM patients, and suggests factors that predict it. Knowing these factors may help clinicians to identify more accurately those RM patients who would be prone to a high level of anxiety and therefore need more attention and reassurance.

Two vs. three or more primary recurrent pregnancy losses--are there any differences in epidemiologic characteristics and index pregnancy outcome?

OBJECTIVE: To compare obstetric characteristics and pregnancy outcomes of patients following two vs. three or more primary recurrent pregnancy losses (RPL). STUDY DESIGN: A retrospective cohort study including 168 patients with primary RPL followed by subsequent (index) pregnancy, 124 patients with three or more consecutive RPL, and 60 patients with two consecutive RPL was performed. All patients were evaluated and treated in the RPL Clinic in the Soroka University Medical Center. RESULTS: Obstetric characteristics of the study groups were similar. Women with three or more RPL compared to women with two RPL had a higher rate of abnormal thyroid stimulating hormone (TSH) levels (16.3 vs. 2.6%; P=0.033), higher rates of spontaneous pregnancy (91.7 vs. 77.4%; P<0.05), and higher rates of Clexane treatment (40.3% vs. 18.6%; P=0.016). In the index pregnancy, live birth rate was not statistically different between the two groups (81.1% in the two-RPL groups vs. 70.6% in the three-RPL group) nor was neonatal mortality. CONCLUSIONS: Patients with two RPL and three RPL had very similar obstetric characteristics and evaluation test results. Differences in index pregnancy outcomes were not statistically significant. Therefore, evaluation in primary RPL is recommended after two RPL.

Primary vs. secondary recurrent pregnancy loss--epidemiological characteristics, etiology, and next pregnancy outcome.

OBJECTIVE: To compare epidemiological and obstetric characteristics, etiology and next pregnancy outcomes of women with primary vs. secondary recurrent pregnancy loss (RPL). STUDY DESIGN: A retrospective cohort study, including 420 patients with two or more consecutive pregnancy losses followed by a subsequent (index) pregnancy, of whom 162 were primary RPL women and 258 were secondary RPL women. All patients were evaluated and treated in the RPL clinic at the Soroka University Medical Center. RESULTS: Live birth rate in the index pregnancy was not statistically different between primary and secondary RPL women (75.9 and 70.9%, respectively). The only significant difference in the etiology evaluation was in abnormal prolactin levels (14.1% of the primary and 1.4% of the secondary RPL group). Women with primary RPL had, at the index pregnancy, significantly higher rates of preterm delivery, fetal growth restriction, and gestational diabetes mellitus. In a multivariable logistic regression analysis, primary RPL adjusted for maternal age and gravidity, was an independent risk factor for preterm delivery compared with secondary RPL [adjusted OR 2.62, CI (95%) 1.30-5.26]. CONCLUSIONS: The prognosis of the two groups was similar regarding live birth rate at the index pregnancy; however, women with primary RPL were more prone to adverse obstetric and neonatal outcomes.

[Psychological and mental aspects and "tender loving care" among women with recurrent pregnancy losses].

Recurrent pregnancy losses (RPL) represent psychological trauma. This may be due to the fact that in about 50% of the cases the etiology is not found and also as a result of the fear of the results of the next pregnancy. Patients with RPL develop different psychological and psychiatric effects after pregnancy losses. This article reviews the Literature on the psychological aspects that develop after RPL, including depression, anxiety, post-traumatic stress disorder (PTSD) and obsessive compulsive disorder (OCD). In addition to psychological effects due to spontaneous pregnancy loss, only a few studies discuss the psychological and psychiatric treatments for these issues. One of the most common and well-accepted forms of treatment, especiaLly for those with idiopathic RPL, is tender Loving care (TLC). Studies have shown that these treatments may have a significant impact on the chance of a live birth rate in the next pregnancy. In the Soroka University Medical Center a very clear protocol exists including supportive care for couples with RPL. In general, the live birth rate for these couples after admitting to the RPL and performing the evaluation is around 80%.

An initial miscarriage is associated with adverse pregnancy outcomes in the following pregnancy.

OBJECTIVE: The objective of the study was to determine whether 1 previous miscarriage is associated with an increased rate of adverse pregnancy outcomes in the following pregnancy. STUDY DESIGN: Second pregnancies of women with and without a miscarriage in their initial pregnancy were compared. Multivariable logistic regression models were constructed to control for confounders. RESULTS: Of 35,125 singleton deliveries in the second pregnancy, 5777 (16.4%) were of patients with an initial miscarriage. Multivariable analysis showed a significant association between a previous miscarriage and the following adverse pregnancy outcomes including premature rupture of membranes (odds ratio [OR], 2.22; 95% confidence interval [CI], 2.01-2.44), preterm delivery (OR, 1.34; 95% CI, 1.21-1.48), intrauterine growth restriction (OR, 1.24; 95% CI, 1.04-1.47), hypertensive disorders (OR 1.41; 95% CI 1.07-1.85), preeclampsia (OR, 1.63; 95% CI, 1.22-2.18), and cesarean delivery (OR, 1.59; 95% CI, 1.46-1.73). Perinatal mortality was significantly higher among women with an initial miscarriage (1.6% vs 1.0%; P < .001). CONCLUSION: An initial miscarriage is independently associated with adverse pregnancy outcomes.

The role of granulocyte colony-stimulating factor in the neutrophilia observed in the fetal inflammatory response syndrome.

OBJECTIVES: Fetal neutrophilia is present in two-thirds of cases with the fetal inflammatory response syndrome (FIRS). The mechanisms responsible for this finding have not been elucidated. Granulocyte colony-stimulating factor (G-CSF) is the primary physiologic regulator of neutrophil production and plays a key role in the rapid generation and release of neutrophils in stressful conditions (i.e., infection). The objective of this study was to determine: 1) whether FIRS was associated with changes in fetal plasma G-CSF concentrations; and 2) if fetal plasma G-CSF concentrations correlated with fetal neutrophil counts, chorioamnionitis, neonatal morbidity/mortality and cordocentesis-to-delivery interval. STUDY DESIGN: Percutaneous umbilical cord blood sampling was performed in a population of patients with preterm labor (n=107). A fetal plasma interleukin-6 (IL-6) concentration >11 pg/mL was used to define FIRS. Cord blood G-CSF was measured by a sensitive and specific immunoassay. An absolute neutrophil count was determined and corrected for gestational age. Receiver operating characteristic (ROC) curve, survival analysis and Cox proportional hazard model were employed. RESULTS: 1) G-CSF was detected in all fetal blood samples; 2) fetuses with FIRS had a higher median fetal plasma G-CSF concentration than those without FIRS (P<0.001); 3) a fetal plasma G-CSF concentration ≥134 pg/mL (derived from an ROC curve) was associated with a shorter cordocentesis-to-delivery interval, a higher frequency of chorioamnionitis (clinical and histological), intra-amniotic infection, and composite neonatal morbidity/mortality than a fetal plasma concentration below this cut-off; and 4) a fetal plasma G-CSF concentration ≥134 pg/mL was associated with a shorter cordocentesis-to-delivery interval (hazard ratio 3.2; 95% confidence interval 1.8-5.8) after adjusting for confounders. CONCLUSIONS: 1) G-CSF concentrations are higher in the peripheral blood of fetuses with FIRS than in fetuses without FIRS; and 2) a subset of fetuses with FIRS with elevated fetal plasma G-CSF concentrations are associated with neutrophilia, a shorter procedure-to-delivery interval, chorio-amnionitis and increased perinatal morbidity and mortality.

Hematologic profile of the fetus with systemic inflammatory response syndrome.

OBJECTIVE: The fetal inflammatory response syndrome (FIRS) is associated with impending onset of preterm labor/delivery, microbial invasion of the amniotic cavity and increased perinatal morbidity. FIRS has been defined by an elevated fetal plasma interleukin (IL)-6, a cytokine with potent effects on the differentiation and proliferation of hematopoietic precursors. The objective of this study was to characterize the hematologic profile of fetuses with FIRS. STUDY DESIGN: Fetal blood sampling was performed in patients with preterm prelabor rupture of membranes and preterm labor with intact membranes (n=152). A fetal plasma IL-6 concentration ≥ 11 pg/mL was used to define FIRS. Hemoglobin concentration, platelet count, total white blood cell (WBC) count, differential count, and nucleated red blood cell (NRBC) count were obtained. Since blood cell count varies with gestational age, the observed values were corrected for fetal age by calculating a ratio between the observed and expected mean value for gestational age. RESULTS: 1) The prevalence of FIRS was 28.9% (44/152); 2) fetuses with FIRS had a higher median corrected WBC and corrected neutrophil count than those without FIRS (WBC: median 1.4, range 0.3-5.6, vs. median 1.1, range 0.4-2.9, P=0.001; neutrophils: median 3.6, range 0.1-57.5, vs. median 1.8, range 0.2-13.9, P<0.001); 3) neutrophilia (defined as a neutrophil count >95th centile of gestational age) was significantly more common in fetuses with FIRS than in those without FIRS (71%, 30/42, vs. 35%, 37/105; P<0.001); 4) more than two-thirds of fetuses with FIRS had neutrophilia, whereas neutropenia was present in only 4.8% (2/42); 5) FIRS was not associated with detectable changes in hemoglobin concentration, platelet, lymphocyte, monocyte, basophil or eosinophil counts; and 6) fetuses with FIRS had a median corrected NRBC count higher than those without FIRS. However, the difference did not reach statistical significance (NRBC median 0.07, range 0-1.3, vs. median 0.04, range 0-2.3, P=0.06). CONCLUSION: The hematologic profile of the human fetus with FIRS is characterized by significant changes in the total WBC and neutrophil counts. The NRBC count in fetuses with FIRS tends to be higher than fetuses without FIRS.

A significant linear association exists between advanced maternal age and adverse perinatal outcome.

OBJECTIVE: The present study was aimed to investigate perinatal outcome of elderly nulliparous patients. STUDY DESIGN: A retrospective study was performed comparing pregnancy outcomes of nulliparous patients at three age groups: less than 35 years (reference group), 35-40 years, and above 40 years. The linear-by-linear association test was used to examine linear association between advanced maternal age and adverse pregnancy outcomes. A multiple logistic regression model was used to control for confounders. RESULTS: Out of 45,033 nulliparous women with singleton gestations, 1,036 were of women over the age of 35, and 188 over 40. A significant linear association was documented between advanced maternal age and adverse outcomes, such as intra uterine growth restriction, low birth weight, congenital malformations, and perinatal mortality. Using a multiple logistic regression model, controlling for gestational age, IUGR and malformations, advanced maternal age was not found to be an independent risk factor for perinatal mortality (adjusted odds ratio = 1.04, 95% confidence interval 0.7-1.4). CONCLUSION: A significant linear association exists between advanced maternal age and adverse maternal and perinatal outcomes. Nevertheless, in our population, advanced maternal age is not an independent risk factor for perinatal mortality.

Factors affecting the latency period in patients with preterm premature rupture of membranes.

OBJECTIVE: The objective of the study was to assess the factors affecting the latency period in woman with preterm premature rupture of membranes (PPROM) and evaluate morbidity associated with prolonged latency. STUDY DESIGN: A population-based retrospective study including all women with PPROM (prior to 37 weeks' gestation) during the years 1998-2008 was conducted. Comparison of the latency period was conducted by the Mann-Whitney U test since the latency period was not normally distributed (most delivered in 24 h). Multivariable logistic regression model was constructed to find independent factors associated with prolonged latency period (>72 h). RESULTS: During the study period, there were 1,399 singleton deliveries of patients with PPROM; 24.6% (345) occurred prior to 34 weeks' gestation. The duration of the latency period was significantly longer among woman with PPROM before 34 weeks as compared to PPROM after 34 weeks' gestation (5.78 vs. 2.02 days; p < 0.001). Other factors associated with longer latency period were multiparity (more than one previous delivery) and maternal age >35. Using a multivariable analysis, the following factors were significantly associated with latency period >72 h: lower gestational age (weeks, OR = 0.8, 95% CI 0.77-0.84; p < 0.001) and multiparity (OR = 1.7, 95% CI 1.3-2.2; p < 0.001). Prolonged latency period (>72 h) was significantly associated with chorioamnionitis (OR = 2.095, 95% CI 1.44-3.04; p < 0.001) and oligohydramnios (OR = 3.041, 95% CI 1.43-6.45; p = 0.004) but not with placental abruption (OR = 0.854, 95% CI 0.41-1.78; p = 0.674) or perinatal mortality (OR = 1.2, 95% CI 0.6-2.2; p = 0.556). CONCLUSION: The duration of the latency period is inversely associated with gestational age. Nulliparity is associated with lower latency period. Prolonged latency is a significant risk factor for chorioamnionitis.

Perinatal outcomes in condyloma acuminata pregnancies.

OBJECTIVE: To investigate pregnancy outcome in patients with condyloma acuminata. METHODS: A retrospective cohort study comparing pregnancy outcome of women with and without condyloma acuminata was performed. A sub-group analysis was performed between patients with localized disease (n = 40), extended disease (n = 25) and no condyloma acuminata (n = 227,202). RESULTS: Using a multivariate logistic regression model, condyloma acuminata was significantly associated with cesarean delivery (OR = 3.4; 95% CI 1.9-5.8; P < 0.001), nulliparity (OR = 4.8; 95% CI 2.6-9.0; P < 0.001), and Jewish ethnicity (vs. Bedouin Arabs; OR = 2.3; 95% CI 1.3-4.1; P < 0.001). A significant linear association was found between the three subgroup (extended condyloma, localized condyloma and no condyloma) and cesarean delivery (40.0% in the extended disease vs. 32.5% in the localized disease vs. 13.0% in the comparison group P < 0.001). No significant differences were noted between the groups in terms of perinatal outcomes, such as low Apgar score (<7) at 1 min (4.2 vs. 1.6%; P = 0.298) and 5 min (0.6 vs. 0.0% P = 0.534) and perinatal mortality (1.4 vs. 1.5% P = 0.912). CONCLUSIONS: Women with condyloma acuminata are at an increased risk for cesarean delivery, while the risk for cesarean delivery is higher for pregnancies with extended when compared with localized disease. Nevertheless, condyloma acuminata is not associated with adverse perinatal outcome.