Oligohydramnios is an independent risk factor for perinatal morbidity among women with pre-eclampsia who delivered preterm.

PURPOSE: The purpose of this study is to determine the relationship between oligohydramnios and adverse maternal and neonatal outcomes in a unique cohort of preterm pre-eclamptic patients. MATERIALS AND METHODS: A retrospective matched case-control study comparing 81 preterm parturients (28 0/7 and 36 6/7 weeks) with pre-eclampsia and oligohydramnios to 81 preterm pre-eclamptic patients with a normal amniotic fluid index (AFI). RESULTS: About 4.8 percent of all our preterm pre-eclamptic patients had oligohydramnios. Patients in the study group showed a trend toward being older than 35 years (18.5%% versus 27.2%) and were more likely more likely to be primi-parous, and have previously delivered a small for gestational age (SGA) or a dead fetus (p = .012, .039, and .032). Severity of pre-eclampsia, including HELLP and eclampsia as well as gestational age at delivery did not differ statistically between the study groups (p = .47, .516). Growth restricted fetuses were more common in the study group (p < .001) but oliguria was more prevalent in patients without oligohydramnios (p = .046). Post-partum complications, pre-eclampsia during the puerperium, admission to intensive care units, and MgSO4 treatment were more common in the control group (p = .028, .012, .008). But study group patients had more cesarean sections (p = .011). Neonates of study group parturients had lower fetal weight, were more likely to be SGA, and experience fetal distress during labor (p = .001, .001, and .03). Following delivery, they were more likely to have anemia and stay longer in neonatal intensive care unit (NICU) (p = .017, .017). A multivariate logistic regression analysis showed that oligohydramnios, but not the severity of pre-eclampsia, significantly affected Composite Neonatal Outcome {Apgar scores at 1 & 5 min (<5 and <7, respectively), neonatal death, umbilical cord pH <7.1, fetal distress (category III fetal heart rate tracing), fetal anemia, fetal hypoglycemia}. CONCLUSIONS: Oligohydramnios is an independent risk factor for early neonatal morbidity in preterm pre-eclamptic patients. AFI <5 cm can be used as one component in the educated decision for delivery of these patients. Brief rationale The significance of oligohydramnios in pregnancies complicated by preterm delivery, preeclampsia or both is controversial. By comparing two relatively large, almost similar, cohorts of preterm preeclamptic parturient with and without oligohydramnios we demonstrated that Amniotic Fluid Index <5 cm is associated with a significant neonatal morbidity. This question was not previously addressed in proper manner aside one, much smaller, study that was under powered to address this topic. We innovate by illustrating the significance of oligohydramnios and its association with subsequent neonatal morbidity. Thus, we conclude that the presence of oligohydramnios in women with preterm preeclampsia can be a factor in the decision for or against conservative management of these patients.

Medically indicated late preterm delivery and its impact on perinatal morbidity and mortality: a retrospective population-based cohort study.

Objective: In the last few decades, attention has been focused on morbidity and mortality associated with late preterm delivery (34-36 + 6/7 weeks), accounting for 60-70% of all preterm births. This study is aimed to determine (1) the prevalence of late preterm deliveries (spontaneous and medically indicated) in our population; and (2) the rate of neonatal morbidity and mortality as well as maternal complications associated with the different phenotypes of late preterm deliveries. Study design: This retrospective population-based cohort study, included 96,176 women who had 257,182 deliveries, occurred between 1988 and 2011, allocated into three groups: term (n = 242,286), spontaneous (n = 10,063), and medically indicated (n = 4833) late preterm deliveries. Results: (1) Medically indicated late preterm deliveries were associated with increased maternal morbidity, as well as neonatal morbidity and mortality, in comparison with other study groups (p < .01 for all comparisons); (2) medically indicated late preterm delivery was an independent risk factor for composite neonatal morbidity (low Apgar score at 5', seizures, asphyxia, acidosis) after adjustment for confounding factors (maternal age and ethnicity and neonatal gender) and stratification according to gestational age at delivery; and (3) the proportion of medically indicated late preterm deliveries affected the neonatal mortality rate. Below 35% of all late preterm deliveries, indicated late preterm birth were associated with a reduction in neonatal mortality; however, above this threshold medically indicated late preterm deliveries were associated with an increased risk for neonatal death. Conclusions: (1) Medically indicated late preterm deliveries were independently associated with adverse composite neonatal outcome; and (2) to benefit in term of neonatal outcome from the tool of medically indicated late preterm birth, their proportion should be kept below 35% of all late preterm deliveries, while exceeding this threshold increases the risk of neonatal mortality.

The pattern and magnitude of "in vivo thrombin generation" differ in women with preeclampsia and in those with SGA fetuses without preeclampsia.

OBJECTIVE: We aimed to determine the differences in the pattern and magnitude of thrombin generation between patients with preeclampsia (PE) and those with a small-for-gestational-age (SGA) fetus. METHODS: This cross-sectional study included women in the following groups: (1) normal pregnancy (NP) (n = 49); (2) PE (n = 56); and (3) SGA (n = 28). Maternal plasma thrombin generation (TGA) was measured, calculating: (a) lag time (LT); (b) velocity index (VI); (c) peak thrombin concentration (PTC); (d) time-to-peak thrombin concentration (TPTC); and (e) endogenous thrombin potential (ETP). RESULTS: (1) The median TPTC, VI, and ETP differed among the groups (p = .001, p = .006, p < .0001); 2) the median ETP was higher in the PE than in the NP (p < .0001) and SGA (p = .02) groups; 3) patients with SGA had a shorter median TPTC and a higher median VI than the NP (p = .002, p = .012) and PE (p < .0001, p = .006) groups. CONCLUSIONS: (1) Patients with PE had higher in vivo thrombin generation than women with NP and those with an SGA fetus; (2) the difference in TGA patterns between PE and SGA suggests that the latter group had faster TGA, while patients with PE had a longer reaction, generating more thrombin. This observation is important for the identification of a subset of patients who might benefit from low molecular-weight heparin.

Late preterm and early term: when to induce a growth restricted fetus? A population-based study.

PURPOSE: (1) Compare fetal and neonatal morbidity and mortality associated with induction of labor (IOL) versus expectant management (EM) in women with isolated fetal growth restriction (FGR) between 340/7 and 386/7 weeks; (2) Determine optimal gestational age for delivery of such fetuses. MATERIALS AND METHODS: A retrospective population based cohort study of 2232 parturients with isolated FGR, including two groups: (1) IOL (n = 1428); 2) EM (n = 804). RESULTS: IOL group had a lower stillbirth and neonatal death rates (p = .042, p < .001), higher 1 and 5 min Apgar scores and a higher vaginal delivery rate compared to the EM group. In the late preterm period, EM was associated with increased rate of low 1 and 5 min Apgar scores, nonreassuring fetal heart rate tracing (NRFHR), stillbirth and neonatal death rate (p = .001, p = .039). In the early term cohort, EM was associated with a higher rate of NRFHR and low 1 min Apgar scores (p = .003, p = .002). IOL at 37 weeks protected from stillbirth but not from adverse composite neonatal outcomes. CONCLUSIONS: IOL of FGR fetuses at 37 weeks had a protective effect against stillbirth. In addition, at late preterm, it is associated with lower rates of stillbirth, neonatal death, and NRFHR.

Tissue factor activity in women with preeclampsia or SGA: a potential explanation for the excessive thrombin generation in these syndromes.

OBJECTIVE: The aim of this study was to determine whether the activity of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the plasma of women with preeclampsia (PE) and small for gestational age (SGA) neonate differ from that of normal pregnant women and whether they are related to specific placental lesions. METHODS: This cross-sectional study included the following groups: (1) normal pregnancy (n = 68); (2) PE (n= 128); and (3) SGA (n = 56). Maternal plasma TF and TFPI activity was determined with chromogenic assays. RESULTS: (1) The median maternal plasma TF activity, but not TFPI activity, differed among the study groups (p < .0001 and p = .4, respectively); (2) patients with PE had a higher median maternal plasma TF activity than women with normal pregnancies (p < .0001) and mothers with SGA fetuses (p = .002); (3) among patients with PE, those with distal villous hypoplasia had a higher median maternal TF activity than those without these placental lesions (p = .018); and (4) following adjustment for confounding variables, maternal plasma TF and TFPI activity were not associated with an SGA neonate. CONCLUSIONS: Plasma TF activity is higher in women with PE than in those with SGA or normal pregnancies. We propose that these changes may be responsible, at least in part, for the increased in-vivo thrombin generation observed in this obstetrical syndrome.

Induction of labor in twin gestation: lessons from a population based study.

INTRODUCTION: The route of delivery and the role of induction of labor in twin gestations are controversial. The aim of this study was to determine the efficacy of induction of labor in twin gestations. METHODS: This retrospective population based cohort study included 4605 twin gestations divided into following groups: 1) spontaneous parturition (n = 2937, 63.78%); 2) induction of labor (n = 653, 14.2%) and 3) elective cesarean delivery (n = 1015, 22.04%). RESULTS: The rate of vaginal delivery in the labor induction group was 81% (529/653). In comparison to the other study groups, induction of labor in twins was independently associated with a 77% reduction in the risk of cesarean delivery (OR 0.23; 95% CI 0.18-0.31) and a 78% reduction in the risk of postpartum death for the second twin (OR 0.22; 95% CI 0.05-0.94). The rate of nulliparity, term delivery and labor dystocia was higher in the induction of labor group (p < 0.001 in all comparisons). CONCLUSIONS: Our results suggest that induction of labor in twin gestation is successful and is independently associated with substantial reduction in the risk of cesarean delivery and postpartum death of the second twin.

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 physiologic anticoagulant and anti-inflammatory role of heparins and their utility in the prevention of pregnancy complications.

Accumulating evidence supports the concept of increased thrombin generation, placental vascular lesions, and inflammation as crucial points in the development of the great obstetrical syndromes [preeclampsia, intrauterine growth restriction (IUGR), preterm labor (PTL), preterm prelabor rupture of membranes (PROM), fetal demise and recurrent abortions]. In light of this, the role of heparins for primary or secondary prevention of these syndromes is becoming more and more apparent, mainly due to the antithrombotic and anti-inflammatory effects of heparins. There is agreement regarding the use of heparin in the prevention of gestational complications in patients with antiphospholipid syndrome, while its use for other obstetrical complications is under debate. In the present review we will describe the physiologic role of heparins on coagulation and inflammation and we will discuss current evidence regarding the use of heparins for the prevention/treatment of obstetrical syndromes.

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.

The physiologic and therapeutic role of heparin in implantation and placentation.

Implantation, trophoblast development and placentation are crucial processes in the establishment and development of normal pregnancy. Abnormalities of these processes can lead to pregnancy complications known as the great obstetrical syndromes: preeclampsia, intrauterine growth restriction, fetal demise, premature prelabor rupture of membranes, preterm labor, and recurrent pregnancy loss. There is mounting evidence regarding the physiological and therapeutic role of heparins in the establishment of normal gestation and as a modality for treatment and prevention of pregnancy complications. In this review, we will summarize the properties and the physiological contributions of heparins to the success of implantation, placentation and normal pregnancy.

A prior placenta accreta is an independent risk factor for post-partum hemorrhage in subsequent gestations.

OBJECTIVE: The rate of placenta accreta, a life threatening condition, is constantly increasing, mainly due to the rise in the rates of cesarean sections. This study is aimed to determine the effect of a history of placenta accreta on subsequent pregnancies. STUDY DESIGN: A population based retrospective cohort study was designed, including all women who delivered at our medical center during the study period. The study population was divided into two groups including pregnancies with: (1) a history of placenta accreta (n=514); and (2) control group without placenta accreta (n=239,126). RESULTS: (1) A history of placenta accreta is an independent risk factor for postpartum hemorrhage (adjusted OR 4.1, 95% CI 1.5-11.5) as were placenta accreta (adjusted OR 22.0, 95% CI 14.0-36.0) and placenta previa (adjusted OR 7.6, 95% CI 4.4-13.2) in the current pregnancy, and a prior cesarean section (adjusted OR 1.7, 95% CI 1.3-2.2); (2) in addition, placenta accreta in a previous pregnancy is associated with a reduced rate of mild preeclampsia in future pregnancies (1.8% vs. 3.4%, RR 0.51, 95% CI 0.26-0.98); (3) however, in spite of the higher rate of neonatal deaths in the study group, a history of placenta accreta was not an independent risk factor for total perinatal mortality (adjusted OR 1.0, 95% CI 0.5-1.9) after adjusting for confounders. CONCLUSION: A history of placenta accreta is an independent risk factor for postpartum hemorrhage. This should be taken into account in order to ensure a safety pregnancy and delivery of these patients.

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.

Placenta accreta is an independent risk factor for late pre-term birth and perinatal mortality.

OBJECTIVE: This study is aimed to identify the risk factors for the development of placenta accreta (PA) and characterize its effect on maternal and perinatal outcomes. STUDY DESIGN: This population-based retrospective cohort study included all deliveries at our medical center during the study period. Those with placenta accreta (n = 551) comprised the study group, while the rest of the deliveries (n = 239 089) served as a comparison group. RESULTS: The prevalence of placenta accerta is 0.2%. Women with this complication had higher rates of ≥2 previous CS (p < 0.001), recurrent abortions (p = 0.03), and previous placenta accreta [p < 0.001]. The rates of placenta previa and peripartum hemorrhage necessitating blood transfusion were higher in women with placenta accreta than in the comparison group. PTB before 34 and 37 weeks of gestation was more common among women with placenta accreta (p < 0.01), as was the rate of perinatal mortality (p < 0.001). Placenta accreta was an independent risk factor for perinatal mortality (adj. OR 8.2; 95% CI 6.4-10.4, p < 0.001) and late PTB (adj. OR 1.4; 95% CI 1.1-1.7, p = 0.002). CONCLUSION: Placenta accreta is an independent risk factor for late PTB and perinatal mortality.

Antenatal diagnosis and treatment of hypothyroid fetal goiter in an euthyroid mother: a case report and review of literature.

Fetal goiter is an extremely rare complication of pregnancy. Its incidence is 1 in 40,000 deliveries. Antithyroid maternal therapy is responsible for 10-15% of fetal congenital hypothyroidism and can be considered as the most frequent underlying cause for this condition. The frequency of fetal goiter that is associated with fetal hypothyroidism and normal maternal thyroid function, as in our case, is even less frequent. Fetal goiter is associated with increased rate of perinatal complications and long-term morbidity, due to peripartum complications including labor dystocia due to its mass effect, as well as neonatal airway obstruction that may lead to hypoxic-ischemic brain injury and death. We present, in this study, a case report of late antenatal fetal goiter in an euthyroid woman and a literature review of the diagnosis and treatment of these cases.

The clinical utility of sonographic cervical length in the management of preterm parturition at 28-32 weeks of gestation.

OBJECTIVES: The aim of this study was to evaluate the role of cervical length measurement in early third trimester (28-32 weeks) as a predictor of preterm delivery (PTD), in women presenting with preterm parturition. METHODS: Cervical length was measured prospectively, in singleton pregnancies at 28-32 weeks with preterm contractions (PTC). A multivariate linear regression model was performed to assess the association between cervical length and gestational age at delivery. Logistic regression analysis with PTD before 34 and 37 weeks of gestation as the outcome variable was performed to control for confounders. RESULTS: Fifty-six women were included, mean gestational week at presentation and at delivery were 29.88 ± 1.13 and 37.05 ± 2.86, respectively. There was a direct association between short cervical length at admission and gestational week at delivery (p = 0.027). This association remained significant even after controlling for confounders. Short cervical length was significantly associated with PTD before 34 (p = 0.045) or 37 (p = 0.046) weeks of gestation. CONCLUSIONS: Third trimester cervical length measurement in patients with PTC is associated with gestational week at delivery, as well as PTD prior to 34 and 37 weeks of gestation. Therefore, examining cervical length is clinically valuable and probably cost-effective during early third trimester.

Index pregnancy versus post-index pregnancy in patients with recurrent pregnancy loss.

OBJECTIVE: To compare pregnancy outcomes of two consecutive pregnancies in a cohort of women with recurrent pregnancy loss (RPL), in order to determine the long-term prognosis of women with RPL managed in a dedicated RPL clinic. METHODS: A retrospective cohort study including 262 patients with two or more consecutive pregnancy losses followed by two subsequent pregnancies--index pregnancy (IP) and post-index pregnancy (PIP). All patients were evaluated and treated in the RPL clinic in the Soroka University Medical Center. RESULTS: Comparing IP with PIP, no significant difference in perinatal outcome was observed. The perinatal outcome remained encouraging with approximately 73% birth rate (73.7% versus 72.5%; p=0.83). Only 11% of the women with RPL continued to experience pregnancy losses for two subsequent pregnancies. In a multivariate logistic regression analysis, number of miscarriages pre-Index was the only factor independently associated with birth in the PIP. CONCLUSION: There is no significant difference between IP and PIP regarding perinatal outcome. Appropriate management in the RPL clinic conferred a significant beneficial effect on long-term pregnancy outcome of a cohort of women with RPL.

Placental vascular pathology and increased thrombin generation as mechanisms of disease in obstetrical syndromes.

Obstetrical complications including preeclampsia, fetal growth restriction, preterm labor, preterm prelabor rupture of membranes and fetal demise are all the clinical endpoint of several underlying mechanisms (i.e., infection, inflammation, thrombosis, endocrine disorder, immunologic rejection, genetic, and environmental), therefore, they may be regarded as syndromes. Placental vascular pathology and increased thrombin generation were reported in all of these obstetrical syndromes. Moreover, elevated concentrations of thrombin-anti thrombin III complexes and changes in the coagulation as well as anticoagulation factors can be detected in the maternal circulation prior to the clinical development of the disease in some of these syndromes. In this review, we will assess the changes in the hemostatic system during normal and complicated pregnancy in maternal blood, maternal-fetal interface and amniotic fluid, and describe the contribution of thrombosis and vascular pathology to the development of the great obstetrical syndromes.

DIC score in pregnant women--a population based modification of the International Society on Thrombosis and Hemostasis score.

OBJECTIVES: The objectives of this study were: 1) To determine the component needed to generate a validated DIC score during pregnancy. 2) To validate such scoring system in the identification of patients with clinical diagnosis of DIC. MATERIAL AND METHODS: This is a population based retrospective study, including all women who gave birth at the 'Soroka University Medical Center' during the study period, and have had blood coagulation tests including complete blood cell count, prothrombin time (PT)(seconds), partial thromboplastin time (aPTT), fibrinogen, and D-dimers. Nomograms for pregnancy were established, and DIC score was constructed based on ROC curve analyses. RESULTS: 1) maternal plasma fibrinogen concentrations increased during pregnancy; 2) maternal platelet count decreased gradually during gestation; 3) the PT and PTT values did not change with advancing gestation; 4) PT difference had an area under the curve (AUC) of 0.96 (p<0.001), and a PT difference ≥1.55 had an 87% sensitivity and 90% specificity for the diagnosis of DIC; 5) the platelet count had an AUC of 0.87 (p<0.001), an 86% sensitivity and 71% specificity for the diagnosis of DIC; 6) fibrinogen concentrations had an AUC of 0.95 (p<0.001) and a cutoff point ≤3.9 g/L had a sensitivity of 87% and a specificity of 92% for the development of DIC; and 7) The pregnancy adjusted DIC score had an AUC of 0.975 (p<0.001) and at a cutoff point of ≥26 had a sensitivity of 88%, a specificity of 96%, a LR(+) of 22 and a LR(-) of 0.125 for the diagnosis of DIC. CONCLUSION: We could establish a sensitive and specific pregnancy adjusted DIC score. The positive likelihood ratio of this score suggests that a patient with a score of ≥26 has a high probability to have DIC.

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.