Asher Bashiri

Cerebral palsy and fetal inflammatory response syndrome : a review

Abstract Cerebral palsy (CP) is the most common cause of severe physical disability in childhood. The precise etiological factor for the development of the majority of cases of CP has not been identified, however, prematurity is considered to be the leading identifiable risk factor. During the last decade, intrauterine infection/inflamation has been identified as the most common cause of preterm delivery and neonatal complications. When microorganisms or their products gain access to the fetus they stimulate the production of cytokines and a systemic response termed FIRS (Fetal Inflammatory Response Syndrome). Subsequently, FIRS was implicated as a cause of fetal or neonatal injury that leads to CP and chronic lung disease. Several authors found an increase in the risk for CP in infants born to mothers with clinical chorioamnionitis, especially in preterm neonates. A relationship between CP and intra-amniotic inflammation was demonstrated, intrauterine infection may lead to activation of the cytokine network which in turn can cause white matter brain damage and preterm delivery, as well as the future development of CP. This white matter insult is identified clinically as periventricular leucomalacia (PVL) which is associated with the subsequent development of impaired neurological outcomes of variable severity including CP.

Hyperemesis gravidarum: epidemiologic features, complications and outcome

During the period of 4 years between 1985 and 1988, 190 patients suffering from hyperemesis gravidarum (HG) were hospitalized at the Soroka Medical Center. From the 190 patients, 164 were followed up throughout their pregnancies and delivered at our Medical Center. The epidemiology of HG as well as the incidence of maternal complications and pregnancy outcome were analyzed and compared with 209 controls. The incidence of HG in our patient population was 6.3/1000 live births. The patients in the study group had fewer pregnancies and deliveries and more spontaneous abortions in the past than in the control population. Premature contractions and vaginal bleeding during the first trimester were more common among women with HG. Other complications of pregnancy were no more common than among controls. Women with HG in their current pregnancy had a lower incidence of spontaneous abortions (3.1%) as compared with previously reported rates in the general population (15%). Perinatal outcome was no different in women with HG than in the controls. Women with severe HG did not have statistically significant differences in the incidence of pregnancy complications and their pregnancy outcome was the same as in those without severe HG.

Prevalence and clinical significance of postpartum endometritis and wound infection.

OBJECTIVE: To correlate clinical variables (gestational age, severe pregnancy-induced hypertension, gestational diabetes mellitus, history of previous cesarean sections, fetal distress, perinatal mortality, postpartum anemia, Apgar score < or = 3 at 1 minute and < or = 7 at 5 minutes, and instrumental delivery) with postpartum endometritis (PPE) and wound infection. METHODS: Descriptive cross-sectional study of the outcome of 75,947 term and preterm singleton deliveries; vaginally and by cesarean section from 1989-1997. RESULTS: The prevalence of PPE after vaginal deliveries was 0.17% (120/68,273). Gestational age of less than 37 weeks, severe pregnancy-induced hypertension, fetal distress, instrumental deliveries, neonatal mortality, postpartum anemia, and Apgar scores of < 7 after 5 minutes were significantly associated with PPE. Gestational diabetes and an Apgar score of < 3 after 1 minute showed similar frequency with and without PPE. The prevalence of PPE after cesarean section was 2.63% (202/7,677). Preterm cesarean sections, history of previous cesarean sections, anemia, and low Apgar scores were seen more frequently with PPE than without. The incidence of cesarean delivery with gestational diabetes mellitus, fetal distress, and perinatal mortality was similar in presence and absence of PPE. The rate of wound infection after cesarean section was 3.97% (318/7,995). Gestational diabetes mellitus, history of previous cesarean deliveries, and low Apgar scores were significantly more frequent with than without wound infection. Gestational age, severe pregnancy-induced hypertension, fetal distress, perinatal mortality, and postpartum anemia were not associated with wound infection. CONCLUSIONS: Awareness of the aforementioned associations may prevent and shorten hospital stay by early diagnosis and appropriate treatment.

Anemia during pregnancy and treatment with intravenous iron: review of the literature.

Anemia, the decrease of the hemoglobin concentration with a consequent decrease in the hematocrit level, is a common disorder complicating pregnancies and is mostly due to iron deficiency. The increase of iron requirements, plasma volume, and the poor intake of iron constitute the principal causes of this deficiency. The present review summarizes the current literature regarding anemia during pregnancy and the parenteral iron therapy options.

Clinical significance and outcome of preterm prelabor rupture of membranes: population-based study

OBJECTIVE To evaluate maternal characteristics and neonatal and maternal birth outcome in cases of prelabor rupture of membranes (PPROM) in a non-selected parturient population. STUDY DESIGN The study population consisted of 5660 singleton preterm births (24-36 weeks gestation) occurring between 1988 and 1997 at the Soroka University Medical Center in Israel. Parturients with no prenatal care were excluded from the study. A cross-sectional study was designed between two groups. The study group consisted of patients with PPROM (n=968) and the comparison group consisted of patients without PPROM (n=4692). The data were analyzed by SPSS package. Information was obtained using a computerized database based on detailed obstetrical records. Logistic regression was used to assess the contribution of different risk factors to PPROM. RESULTS PPROM was associated with a significantly lower gestational age (24-32 weeks) and birth weight (<2500 g) than those with intact membranes. The rates of chorioamnionitis and urinary infection were found significantly higher in the PPROM group compared with women without PPROM (16.5 vs. 2.7%; 5.1 vs. 3.3%, respectively) (P<0.001). The rate of endometritis and bacteremia in the postpartum period were significantly higher in women with PPROM compared with controls 2.8 vs. 1.4%, (P=0.003) and 9.4 vs. 5%, (P=0.001), respectively. Total perinatal mortality rates were significantly higher in the group without PPROM 10.5 vs. 7.2% (P=0.01), however, rates of postpartum death were higher in the PPROM group 5.5 vs. 4% (P<0.01). When adjusted for recognized risk factors using logistic regression analysis, infection of amniotic fluid (OR=6.6) and genito-urinary tract infection (OR=1.64) remained the independent risk factors associated with PPROM. CONCLUSIONS Infectious morbidity in patients with preterm prelabor rupture of membranes and preterm delivery remained an important risk factor for obstetrical and neonatal complications.

Pregnancy outcome of asthmatic patients: A population-based study

Objective. To investigate pregnancy outcome of asthmatic patients. Methods. A retrospective population-based study comparing all singleton pregnancies in women with and without asthma was conducted. Patients lacking prenatal care (less than three visits in prenatal care facilities) were excluded from the study. Deliveries occurred during the years 1988–2002. Stratified analysis, using a multiple logistic regression model was performed to control for confounders. Results. During the study period 139 168 singleton deliveries occurred, of which 1.4% in asthmatic patients (n = 963). Using a multivariate analysis, with backward elimination, the following complications were significantly associated with maternal asthma: diabetes mellitus (OR = 1.8, 95%CI 1.5–2.0, p < 0.001), fertility treatments (OR = 1.6, 95%CI 1.3–2.1, p < 0.001), intrauterine growth restriction (IUGR) (OR = 1.5, 95%CI 1.1–1.9, p = 0.004), hypertensive disorders (OR = 1.5, 95%CI 1.2–1.7, p < 0.001) and premature rupture of membranes (OR = 1.2, 95%CI 1.1–1.5, p = 0.013). Higher rates of cesarean deliveries were found among asthmatic patients as compared to the controls (17.1% vs. 11.4%, p < 0.001). This association persisted even after controlling for possible confounders such as failure to progress in labor, mal-presentations, IUGR, etc. No significant differences regarding low Apgar scores (less than 7) at 1 and 5 minutes were noted between the groups (3.9% vs. 4.4%, p = 0.268 and 0.4% vs. 0.6%, p = 0.187, respectively). Likewise, the perinatal mortality rate was similar among patients with and without asthma (1.3% vs. 1.3%, p = 0.798). Conclusion. Pregnant women with asthma are at an increased risk for adverse maternal outcome. This association persists after controlling for variables considered to co-exist with maternal asthma. However, perinatal outcome is favorable. Careful surveillance is required in pregnancies of asthmatic patients, for early detection of possible complications.

Prevalence and Clinical Significance of PostpartumEndometritis and Wound Infection

OBJECTIVE To correlate clinical variables (gestational age, severe pregnancy-induced hypertension, gestational diabetes mellitus, history of previous cesarean sections, fetal distress, perinatal mortality, postpartum anemia, Apgar score < or = 3 at 1 minute and < or = 7 at 5 minutes, and instrumental delivery) with postpartum endometritis (PPE) and wound infection. METHODS Descriptive cross-sectional study of the outcome of 75,947 term and preterm singleton deliveries; vaginally and by cesarean section from 1989-1997. RESULTS The prevalence of PPE after vaginal deliveries was 0.17% (120/68,273). Gestational age of less than 37 weeks, severe pregnancy-induced hypertension, fetal distress, instrumental deliveries, neonatal mortality, postpartum anemia, and Apgar scores of < 7 after 5 minutes were significantly associated with PPE. Gestational diabetes and an Apgar score of < 3 after 1 minute showed similar frequency with and without PPE. The prevalence of PPE after cesarean section was 2.63% (202/7,677). Preterm cesarean sections, history of previous cesarean sections, anemia, and low Apgar scores were seen more frequently with PPE than without. The incidence of cesarean delivery with gestational diabetes mellitus, fetal distress, and perinatal mortality was similar in presence and absence of PPE. The rate of wound infection after cesarean section was 3.97% (318/7,995). Gestational diabetes mellitus, history of previous cesarean deliveries, and low Apgar scores were significantly more frequent with than without wound infection. Gestational age, severe pregnancy-induced hypertension, fetal distress, perinatal mortality, and postpartum anemia were not associated with wound infection. CONCLUSIONS Awareness of the aforementioned associations may prevent and shorten hospital stay by early diagnosis and appropriate treatment.

Congenital anomalies are an independent risk factor for neonatal morbidity and perinatal mortality in preterm birth.

OBJECTIVE To determine whether congenital anomalies are associated with a high rate of neonatal morbidity in preterm birth. STUDY DESIGN 312 singletons (22-36 wk) with congenital anomalies that were delivered preterm were compared with a random sample of 936 preterm singleton without congenital anomalies. Data was obtained using the computerized birth discharge records. Statistical analysis included univariate and multivariate logistic regression analyses. RESULTS Three thousand five hundred and seventy-eight (3578) women with preterm births met the inclusion criteria (singleton with prenatal care). The prevalence of congenital anomalies in the study population was 8.7% (312/3578). Gestational age at delivery was significantly lower in the congenital anomaly group compared with the control (32.0+/-3.7 SD vs. 34.4+/-2.7 SD; p<0.001). The following pregnancy complications were higher in the group with congenital anomalies than in those without anomalies: severe pregnancy induced hypertension (PIH), hydramnions, oligohydramnion, intrauterine growth restriction (IUGR), fetal distress, cesarean section, malpresentation and mal position, abruption placenta, meconium stained amniotic fluid, 1 min Apgar score (<2), 5 min Apgar score (<7). Perinatal mortality rates in 28-32 wk and 33-36 wk were significantly higher in the group with congenital anomalies than in the control group. Neonatal morbidity data (necrotizing enterocolitis, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, and sepsis) was available for 909 neonates (239 with congenital anomalies and 670 without congenital anomalies). After adjusting for gestational age, the presence of congenital anomalies remained strongly associated with neonatal morbidity (having one or more of the above mentioned conditions) (adjusted OR: 5.3, 95% CI 3.4-9.2). When adjusting for other confounding variables, congenital anomalies were strongly associated with neonatal morbidity (OR: 6.44, 95% CI 3.94-10.51), and perinatal mortality (OR: 3.08, 95% CI 2.04-4.65). In terms of attributable fraction in our population of preterm births, the proportion of neonatal morbidity and the proportion of perinatal mortality attributable to congenital malformation is 32% and 15%, respectively. CONCLUSION Congenital anomalies in preterm birth are associated with a higher rate of pregnancy complications and are an independent risk factor for neonatal morbidity and perinatal mortality.

Elevated concentrations of interleukin-6 in intra-amniotic infection with Ureaplasma urealyticum in asymptomatic women during

BACKGROUND Intra-amniotic infection is an important cause of preterm delivery and interleukin-6 (IL-6) determination was recently applied for identification of microbial invasion of the amniotic cavity. Our aim was to determine the levels of IL-6 in culture-positive amniotic fluids at genetic amniocentesis and to evaluate their significance in relation to pregnancy outcome. METHODS Seven culture-positive and 23 culture-negative amniotic fluids, obtained at 17-19 weeks of gestation, were analyzed for IL-6 levels by an immunoassay (ELISA). Pregnancy outcomes of all 30 women were obtained from the medical charts. RESULTS The mean level of IL-6 in the culture-negative amniotic fluids was 78+/-206 pg/ml. Among the seven culture-positive, high levels of IL-6 were found only in three amniotic fluids that were culture-positive for Ureaplasma urealyticum (1834, 1342 and 2832 pg/ml). Low levels of IL-6, ranging from zero to 60 pg/ml, were found in four AFs that were culture-positive for Staphylococcus epidermidis (n=3) and Bacillus Gram-positive (n= 1). Adverse pregnancy outcome occurred in the three women who had intra-amniotic infection with U. urealyticum accompanied by high levels of IL-6 (two fetal loss and one preterm delivery at 28 weeks of gestation). The four women with culture-positive but IL-6 negative amniotic fluids, had normal pregnancy outcome and term delivery. Two of the 23 women with culture-negative had preterm delivery, one with high (1000 pg/ml) and one with low (80 pg/ml) levels of IL-6. CONCLUSION High levels of IL-6 are suggestive of a genuine intra-amniotic infection with urea-plasmas resulting in adverse pregnancy outcome, while culture-positive amniotic fluids with normal IL-6 levels, may suggest a state of contamination.

Maternal Hypertensive Disorders Are an Independent Risk Factor for the Development of Necrotizing Enterocolitis in Very Low Birth Weight Infants

Objective: The purpose of this study was to compare complications and outcome of preterm neonates weighing ≤1,500 g who developed necrotizing enterocolitis (NEC) to neonates without NEC. Study Design: During January, 1995 to December, 1998, 211 live preterm neonates were born with birth weight ≤1,500 g. A cross sectional prospective study was designed and two groups were defined: 17 neonates who developed NEC and 194 without NEC. Multiple logistic regression analysis was performed to determine independent risk factors for the development of NEC. Results: The prevalence of NEC was 8% (17/211). The following complications were found to be significantly higher among mothers of neonates with NEC: mild pre-eclampsia (11.8 vs. 2.6%, p = 0.04); severe pre-eclampsia (35.5 vs. 12.9%, p = 0.01); chronic hypertension (29.4 vs. 5.7%, p < 0.001) and low birth weight (968 ± 233 vs. 1,123 ± 257 g, p = 0.02). In contrast, mean maternal age, mean gestational age at delivery and parity were not significantly different between the groups. A multivariate analysis including the following factors: maternal hypertensive disorders, pregestational diabetes mellitus, birth weight and gestational age at delivery, found only maternal hypertensive disorders to be independent risk factors for NEC (OR = 5.21, 95% CI 1.64–16.58). Conclusions: Maternal hypertension is an independent risk factor for the development of NEC in preterm neonates weighing <1,500 g. Thus, maternal vascular disorders may play an important role in the pathophysiology of NEC.