Objective We sought to determine whether cervicovaginal fluid matrix metalloproteinase-l and -9 (MMP-1 and MMP-9) levels differed during pregnancy compared with those at term or in preterm labor. Study design We used sensitive immunoassays to measure MMP-1 and MMP-9 levels in cervicovaginal secretions. Cases (n = 32) included women who delivered preterm, and were sampled more than 3 weeks prior to delivery (n = 19), within 1 week of delivery (n = 7), and during spontaneous labor (n = 6). Controls consisted of 80 women matched for race, age and gestational age, delivering at term and who were sampled at 20-32 weeks (n = 47), within I week of delivery (n = 14) and during term labor (n = 19). Results Among cases and controls, cervicovaginal MMP-1 levels were low and unaffected by labor. Among non-laboring control patients, the median and range of MMP-9 concentrations were also low (0; 0-0.04 ng/ml), and these remained unchanged with advancing gestational age. However, MMP-9 levels increased significantly within 1 week of term labor (0.8; 0-22.8 ng/ml; p = 0.001) and during term labor (6.6; 0-30.6 ng/ml; p = 0.04), with the highest values observed among laboring patients with ruptured membranes (24.8; 19.2-30.6 ng/ml; p = 0.002). Among cases, MMP-9 concentrations were unaltered prior to preterm labor, but increased among patients in preterm labor (0.3; 0-30 ng/ml; p = 0.02). Conclusion Cervicovaginal MMP-1 levels were low and unchanged during either preterm or term labor. In contrast, MMP-9 levels increased during term and preterm labor but did not predict preterm delivery in asymptomatic patients.
Objectives This study assessed the correlation between early embryonic growth and maternal glycemia, as well as between early embryonic growth restriction and incidence of spontaneous abortions and of congenital malformations. Methods The prospective study included 102 pregnant women with insulin-dependent diabetes mellitus and 192 matched healthy controls. All women had regular periods. The level of serum chorionic gonadotropin was determined at least twice: at 6-8 weeks of pregnancy and before 12 weeks of pregnancy. A single measurement of maternal glycosylated hemoglobin, two ultrasound examinations and multiple measurements of blood glucose levels were performed between 6 and 12 weeks of pregnancy. Pregnancies were classified into groups with normal and restricted embryonic growth according to ultrasound fetal biometry. Differences in glycemia between groups, incidence of spontaneous abortions and congenital malfomations were calculated. Results Early embryonic growth restriction was significantly more frequent in diabetic pregnancies. Poor maternal metabolic control in diabetic pregnancies, measured as raised glycosylated hemoglobin level, was correlated with early embryonic growth restriction. The group of pregnancies with restricted embryonic growth also showed a significantly higher incidence of spontaneous abortions, and the correlation with congenital malformations was marginally significant. Conclusions Our results support the hypothesis that the level of maternal blood glucose immediately prior to conception and during early embryonic development may directly affect human embryonic and consequently fetal development. The number of embryopathies in diabetic pregnancies could be reduced if normoglycemia were maintained in these periods.
Aims To investigate the level of lipid peroxidation products- malondialdehyde and Schiff bases - the parameters of oxidative stress, in different tissues. The study also aimed at evaluation of the proportions of these parameters in physiological pregnancy, to determine oxidative stress that is not accompanied by anoxia symptoms. Methods The study was performed at the Department of Obstetrics, Institute of Gynecology and Obstetrics in Lodz, in 1999-2000. It comprised 42 pregnant women between the 38th and 40th weeks of pregnancy. They were all under constant out-patient care and were admitted to the Obstetrics Department at delivery. In each case, Cesarean section was performed before labor started. The concentrations of the most important aldehyde product of polyunsaturated fatty acid degradation (malondialdehyde; MDA) and malondialdehyde conjugation products with amine organic groups (Schiff bases) were determined with spectrophotometry and fluorimetry. Results The mean MDA concentration in uterine muscle homogenates was 7.29 +/-1.36nmol/ml; in placenta homogenates it was 9.55 +/- 0.73 nmol/ml. The concentration of amniotic fluid MDA was 1.53 +/- 0.59 nmol/ml, in peripheral blood serum of pregnant women it was 2.67 +/- 0.85 nmol/ml and in the umbilical cord artery serum it was 9.55 +/- 1.20 nmol/ml. Schiff base concentration was 22.67 +/- 7.6 arbitrary fluorescence units (AU) in peripheral blood serum of pregnant women, 9.07 +/- 2.9 AU in uterine muscle homogenates, 7.71 +/-2.2 AU in homogenized placenta samples, 23.14 +/-3.2 AU in amniotic fluid, 13.87 +/-2.4AU in umbilical artery serum and 17.22 +/- 1.7 AU in umbilical vein serum. Conclusions We observed significant differences between MDA and Schiff base concentrations in the umbilical artery and vein serum. MDA levels in placenta homogenates were significantly increased compared with uterine muscle homogenates. The mean levels of Schiff bases in uterine homogenates were significantly higher than those found in placenta homogenates.
Objective To describe six cases of severe acidosis (umbilical artery pH < 7.00) at birth with normal neurological outcome, and to review the available world literature. Methods Six singleton term neonates with a sudden sentinel intrapartum 'hypoxic event', severe acidosis, and normal neurological outcome were retrospectively evaluated. Results The sudden sentinel intrapartum events were due to amniotic fluid embolus (n = 3), uterine rupture, (n = 1), abruption/bradycardia (n = 1), and unknown (n = 1). At birth, these six infants had a mean artery pH of 6.79 +/- 0.09, with a range of 6.67-6.91, and a base deficit of 17 +/- 7 mEq/l, with a range of 11-16 mEq/l. The last neonatal evaluations which ranged from 1 to 11 years were all normal. When these infants were contrasted with the world literature, persistent fetal brain injury was more commonly associated with an absence of severe acidosis. Conclusions Our findings, when combined with a review of available literature, suggest that severe acidosis may be an improper endpoint to study intrapartum asphyxia or to determine whether a fetus has sustained intrapartum brain damage.
Cardiovascular compromise in critically ill preterm and term infants initially presents with the 'compensated phase' of shock characterized by oliguria, poor peripheral perfusion and normal blood pressure. As the condition worsens, the failure of the neuroendocrine compensatory mechanisms results in the development of hypotension and, in more advanced cases, lactic acidosis. In this 'uncompensated phase' of shock, the imbalance between tissue oxygen delivery and oxygen demand leads to gradually advancing cellular damage and organ dysfunction. In clinical practice, neonatal shock is most frequently recognized in its uncompensated phase by the presence of hypotension. However, although close to half of the newborns admitted to neonatal intensive care units receive treatment for hypotension, the normal physiological blood pressure range ensuring appropriate organ perfusion in the newborn is unknown. Therefore, the decision to treat hypotension and thus uncompensated shock in the newborn is based on statistically defined gestational-age- and postnatal-age-dependent normative blood pressure values and physicians' beliefs rather than on data bearing physiological reference. Since, in the majority of newborns, especially in the immediate postnatal period, shock is primarily caused by impaired regulation of peripheral vascular tone with or without myocardial dysfunction, dopamine is the primary drug of choice; it is more effective than dobutamine in raising blood pressure. However, in some cases with primary myocardial dysfunction and elevated systemic vascular resistance, a more appropriate balance between myocardial contractility and afterload may be achieved by the use of dobutamine. Since absolute hypovolemia is a less frequent cause of shock in the newborn, volume administration has been shown to be less effective in the immediate postnatal period and its extensive use is associated with significant untoward effects, especially in preterm infants. During the course of their disease, some of the sickest hypotensive newborns become unresponsive to volume and presser administration. This phenomenon is caused by the desensitization of the cardiovascular system to catecholamines by the critical illness and relative or absolute adrenal insufficiency. The findings that steroids rapidly up-regulate cardiovascular adrenergic receptor expression and serve as hormone substitution in cases of adrenal insufficiency explain their effectiveness in stabilizing the cardiovascular status and decreasing the requirement for presser support in the critically ill newborn with volume- and presser-resistant hypotension. Finally, despite recent advances in our understanding of the pathophysiology and management of neonatal shock, there is little information on the impact of the treatment on organ blood flow and tissue perfusion and on neonatal morbidity and mortality.
Objective The aim of this study was to determine our anomaly prevalence in a low-risk population, to observe the distribution of anomalies detected by ultrasound and to evaluate the accuracy of the antenatal detection of malformations by second-level ultrasound examination during weeks 16-24 of gestation. Materials and methods Antenatal follow-up of 8420 pregnant women was performed at the antenatal unit of the Zeynep Kamil maternity hospital from May 1996 to July 1998. All women underwent a screening ultrasonographic examination of fetal anatomy at 16-24 weeks of gestation. The distribution of detected anomalies according to organ systems, the incidence of anomalous infants, the prevalence of fetal anomalies and the sensitivity and specificity were evaluated. Results During the study period of 27 months, 160 anomalies were recorded in 110 fetuses. It was found that the anomaly prevalence was 1.58%; the positive and negative predictive values were 89.6% and 99.8%, respectively. Our detection rates of fetal anomalies were 92.3% for the central nervous system, 80% for the musculoskeletal system, 61.5% for the genitourinary system, 50% for craniofacial anomalies and 23.5% for the cardiovascular system. Conclusion Second-level ultrasound scanning at 16-24 weeks of gestation should be an essential procedure for diagnosing prenatal malformations. It reveals important data when performed in tertiary centers by educated and experienced sonographers with a uniform program.
Objective This survey was conducted to assess the knowledge, beliefs and practice behaviors of obstetrician-gynecologists concerning their patients' prenatal use of tobacco and other drugs.Methods We developed a 32-item questionnaire which the American College of Obstetricians and Gynecologists mailed to a sample of 1000 members throughout the USA. A total of 604 questionnaires were returned (60%). Descriptive statistics, prevalence rates and prevalence rate ratios were calculated, and stratified analyses were performed in some cases in order to control for the possible confounding effects of age and gender.Results Most respondents (98%) reported questioning their prenatal patients at the first visit about tobacco use, with only one in nine asking at each prenatal visit. Ninety-five per cent of respondents reported that they discussed adverse effects and advised cessation for patients who screened positive for smoking; 38% reported always providing self-help materials; and 22% reported referrals to cessation workshops. Fewer respondents (87%) reported asking their patients about drug use. Among women reporting other drug use, 97% of clinicians discussed adverse effects, and 95% advised abstinence. Forty-five per cent reported that they referred patients for treatment, and one-third reported performing periodic drug screens. Respondents graduating after 1989, female clinicians and clinicians who judged their medical school training on substance use as excellent or very good were more likely to adhere to current practice guidelines on smoking and illicit drug use.Conclusions While screening of prenatal patients for tobacco use and other drug use was reported by survey respondents, providing or arranging for interventions for those screening positive was less often reported.
Aims The objective of the present study was to examine whether umbilical cord vessels are less responsive to vasoconstricting agents in the presence of acidosis. We speculated that some of the cases of cord prolapse during labor might be related to a lower 'baseline' tone of the umbilical vessels secondary to pre-existing fetal acidosis. Materials and methods Umbilical cord segments obtained from uncomplicated pregnancies at term were incubated under in vitro conditions. Maximal responses to 120 mmol/l potassium HEPES and dose response to 5-hydroxytryptamine (5-HT) were measured under different pHs (7.4, 7.2, 7.0, 6.8) of the HEPES solution. Results There was a marked decrease in maximum response to 5-HT and a decrease in the Hill coefficient in response to 5-HT as the pH in the bath decreased. Conclusion The in vitro response of umbilical cord vessels to a vasoconstrictor decreased as pH decreased. We speculate that changes in the pH, within the range observed in fetal acidosis, could alter the firmness of the umbilical cord. We propose that some fetuses could experience cord prolapse secondary to a pre-existing undiagnosed fetal acidemia.
We report an infant with Noonan syndrome who presented antenatally with polyhydramnios, edema, ascites and pericardial effusion. His mother has Noonan syndrome. Postnatally, he was found to have clinical features compatible with Noonan syndrome, and a right-sided pleural effusion was noted. This resolved by day 12 without any intervention. This case is an example of the diversity of clinical features of Noonan syndrome.
Objective The aim of this study was to evaluate the role of prenatal markers (biochemical, ultrasonographic and Doppler parameters) in screening for chromosomal abnormalities at 10-16 weeks' gestation. We evaluated the effectiveness of combined parameters in order to suggest the optimal strategy in low- and high-risk populations. Methods Biochemical serum assessment (risk assessed by maternal age and biochemical markers-pregnancy-associated plasma protein A (PAPP-A) and total beta -human chorionic gonadotropin (beta -hCG) between 10 and 12 weeks, cc-fetoprotein (AFP) and total beta -hCG between 13 and 16 weeks), nuchal translucency (NT) measurement, fetal heart rate (FHR), umbilical artery pulsatility index (PI) and ductus venosus PI for veins were prospectively evaluated. A total of 7718 pregnant women between 10 and 16 weeks' gestation were included. We used the 95th centile as a cut-off level for NT, umbilical artery PI and ductus venosus PI for veins, the 2.5 and 97.5th centiles as cut-off levels for FHR, and estimated risk for Down's syndrome of > 1/270 as a cut-off level for biochemical assessment combined with maternal age. Results Chromosomal abnormalities were found in 76 cases (35 cases of trisomy 21). Seventy-six per cent of the population was younger than 35 years. The overall detection rate, specificity, positive predictive value (PPV), negative predictive value (NPV) and odds ratio (OR) for aneuploidy were 75%, 95.6%, 14.5%, 99.7% and 65, respectively, when using NT measurement as a single criterion. Using the ductus venosus PI for veins, the overall detection rate, specificity, PPV, NPV and OR for aneuploidy were 81.5%, 95.6%, 15.3%, 99.8% and 95, respectively. We evaluated the effectiveness of two combined strategies for chromosomal abnormality detection: selective screening (NT and ductus venosus PI for veins) and overall screening tall markers). Using NT and the ductus venosus PI for veins, the detection rate was 47.5% for ail chromosomal abnormalities, increasing to 68.2% for autosomal trisomies, with a specificity of 99.8%. Using all sonographic and Doppler markers simultaneously, the detection rate was 100% with a 29.7% false-positive rate. Conclusions We conclude that early screening programs for chromosomal abnormalities (10-16 weeks) are at least as effective as later strategies (16-20 weeks). In our study, NT was the most sensitive and specific marker for autosomal trisomies, while the ductus venosus PI for veins was the most sensitive and specific marker for chromosomal abnormalities as a whole. However, the umbilical artery PI and FHR were not effective single markers for chromosomal abnormalities. They may have a role in combined strategies, as markers of lethal autosomal trisomies. Finally, biochemical serum strategies should be reconsidered when an unselected population is screened early.
This study analyzed the role of the UDP-glucuronosyltransferase (UCT1A1) promoter polymorphism (mutant A[TA](7)TAA versus wild-type A[TA](6)TAA) in the pathophysiology of non-physiological hyperbilirubinemia, in Caucasian Portuguese neonates. Typing for the TATA box polymorphism was carried out in a study group consisting of 77 jaundiced neonates (19 with physiological and 58 with non-physiological hyperbilirubinemia) and in a background control population consisting of 100 healthy non-jaundiced Caucasian neonates. In the hyperbilirubinemic group without identified risk factors (n = 54), we found 50% normal homozygotes ([TA](6)/[TA](6)), 33.4% heterozygotes ([TA](6)/ [TA](7)), 14.8% mutant homozygotes ([TA](7)/[TA](7)) and a single heterozygote with a TA deletion ([TA](5)/[TA](6)). No statistically significant difference was found between this genotype distribution and that observed in the control group (chi (2) =1.585; p > 0.05). There was also no significant difference in genotype distribution between neonates with physiological and non-physiological hyperbilirubinemia (chi (2) = 3.156; p > 0.05), neither were peak jaundice levels significantly different among the various genotypic groups (chi (2) = 1.469; p > 0.05) except in the jaundiced population with associated risk factors. Our results indicate that the TATA box polymorphism did not seem to be a major contributing factor to the development of neonatal hyperbilirubinemia in our population but, when associated with other risk factors, seemed to influence the peak jaundice levels.
We report a case of neonatal jaundice due to fetomaternal incompatibility in the ABO system, the investigation of which demonstrated thrombocytopenia (69 x 10(9)/l) without evidence of hemorrhage. Further investigations revealed a maternal platelet count of 16 x 10(9)/l with multiple platelet clumps in the peripheral blood smear. The ethylenediaminetetra-acetic acid (EDTA)-dependent nature of the thrombocytopenia was confirmed both in the mother and in the neonate. After 45 days, the infant's platelet count returned to normal even in the presence of EDTA, whilst thrombocytopenia persisted in the mother. This case poses the need to consider this possibility in neonates with low platelet counts without hemorrhagic symptoms, in order to avoid additional investigations and inappropriate treatments.
