Sodium influx blockade and hypoxic damage to CA1 pyramidal neurons in rat hippocampal slices.

We studied the effects of lidocaine and tetrodotoxin (TTX) on hypoxic changes in CA1 pyramidal neurons to examine the ionic basis of neuronal damage. Lidocaine (10 and 100 microM) and TTX (6 and 63 nM) delayed and attenuated the hypoxic depolarization and improved recovery of the resting and action potentials after 10 min of hypoxia. Lidocaine (10 and 100 microM) and TTX (63 nM) reduced the number of morphologically damaged CA1 cells and improved protein synthesis measured after 10 min hypoxia. Lidocaine (10 microM) attenuated the increase in intracellular sodium (181 vs. 218%) and the depolarization (-21 vs. -1 mV) during hypoxia but did not significantly attenuate the changes in ATP, potassium, or calcium measured at 10 min of hypoxia. Lidocaine (100 microM) attenuated the changes in membrane potential, sodium, potassium, ATP, and calcium during hypoxia. TTX (63 nM) attenuated the changes in membrane potential (-36 vs. -1 mV), sodium (179 vs. 226%), potassium (78 vs. 50%), and ATP (24 vs. 11%) but did not significantly attenuate the increase in calcium during hypoxia. These data indicate that the primary blockade of sodium channels can secondarily alter other cellular parameters. The hypoxic depolarization and the increase in intracellular sodium appear to be important triggers of hypoxic damage independent of their effect on cytosolic calcium; a treatment that selectively blocked sodium influx (lidocaine 10 microM) improved recovery. Our data indicate that selective blockade of sodium channels with a low concentration of lidocaine or TTX improves recovery after hypoxia by attenuating the rise in cellular sodium and the hypoxic depolarization. This blockade improves the resting and action potentials, histologic state, and protein synthesis of CA1 pyramidal neurons after 10 min of hypoxia to rat hippocampal slices. A higher concentration of lidocaine, which also improved ATP, potassium, and calcium concentrations during hypoxia was more potent. In conclusion, the depolarization and increased sodium concentration during hypoxia account for a portion of the neuronal damage after hypoxia independent of changes in calcium.

Occupational fatigue and preterm premature rupture of membranes. National Institute of Child Health and Human Development Maternal-Fetal Medicine, Units Network.

OBJECTIVE: The aim of this study was to prospectively determine the relationship between occupational fatigue and spontaneous preterm delivery segregated into the etiologically distinct categories of spontaneous preterm labor, preterm premature rupture of membranes, and indicated preterm delivery. STUDY DESIGN: A total of 2929 women with singleton pregnancies at 22 to 24 weeks' gestation were enrolled in a multicenter (10 sites) Preterm Prediction Study. Patients reported the number of hours worked per week and answered specific questions designed to determine the following 5 sources of occupational fatigue described by Mamelle et al: posture, work with industrial machines, physical exertion, mental stress, and environmental stress. Fatigue was quantified (0-5 index) according to the number of these sources positively reported. Simple and Mantel-Haenszel chi2 tests were used to test the univariate association and hypothesis of a linear trend between sources of occupational fatigue and spontaneous preterm delivery. Covariables were considered by multivariate logistic regression analysis. Women who did not work outside the home were considered separately from those who worked but did not report any sources of occupational fatigue. RESULTS: Each source of occupational fatigue was independently associated with a significantly increased risk of preterm premature rupture of membranes among nulliparous women but not among multiparous women. The risk of preterm premature rupture of membranes increased (P = .002) with an increasing number of sources of occupational fatigue-not working outside the home, 2.1%; working but not reporting fatigue, 3.7%; working with 1 source of fatigue, 3.2%; working with 2 sources of fatigue, 5.2%; working with 3 sources of fatigue, 5.1%; and working with 4 or 5 sources of fatigue, 7.4%. There was also a significant relationship (P = .01) between preterm premature rupture of membranes and an increasing number of hours worked per week among nulliparous women. Neither spontaneous preterm labor nor indicated preterm delivery was significantly associated with occupational fatigue among either nulliparous or multiparous women. CONCLUSION: The occupational fatigue index of Mamelle et al discriminated a group of nulliparous women at increased risk for preterm premature rupture of membranes. The relationship between preterm premature rupture of membranes and occupational fatigue or hours worked may provide guidelines according to which nulliparous women and their employers can be advised.

Birth weight references for twins.

OBJECTIVE: We sought to formulate fetal and birth weight references for twins from longitudinal data. STUDY DESIGN: This historic cohort study was based on 1831 pregnancies of twins born alive at >/=28 weeks' gestation from Baltimore, Maryland; Miami, Florida; Charleston, South Carolina; and Ann Arbor, Michigan. RESULTS: When we compared singletons and twins, the percentiles of twins fell substantially below the 10th percentile of singletons by 28 weeks' gestation, below the 50th percentile by 30 weeks' gestation, and below the 90th percentile by 34 weeks' gestation. The difference at the 50th percentile was 147 g (10%) at 30 weeks' gestation, 242 g (14%) at 32 weeks' gestation, 347 g (17%) at 34 weeks' gestation, 450 g (19%) at 36 weeks' gestation, 579 g (22%) at 38 weeks' gestation, and 772 g (27%) at 40 weeks' gestation. CONCLUSION: This new reference demonstrates that, although the overall pattern of fetal growth is slower for twins versus singletons from about 30 weeks' gestation, well-grown twins and singletons do not differ as much as previously believed.

Recent indomethacin tocolysis is not associated with neonatal complications in preterm infants.

OBJECTIVE: We sought to determine whether indomethacin tocolysis immediately before delivery is associated with any increased complications in neonates delivered between 24 and 32 weeks' gestation. STUDY DESIGN: We performed a case-control analysis of neonates delivered between 24 and 32 weeks' gestation after maternal indomethacin treatment for preterm labor. All infants were delivered within 48 hours of indomethacin exposure. Seventy-five patients were matched with 150 control subjects in a patient/control ratio of 1:2. Matching variables in order of priority included gestational age at delivery, fetal number, betamethasone exposure >24 hours before delivery, magnesium sulfate use, mode of delivery, infant sex, and race. Data were analyzed by using the Student t test, chi(2) analysis, and the Fisher exact test and Yates' correction. RESULTS: The gestational age at delivery (mean +/- SD) was 28.7 +/- 2.3 weeks in the indomethacin group and 28.3 +/- 2.1 weeks for the control subjects. Birth weights (mean +/- SD) were 1121 +/- 243 and 1141 +/- 287 g, respectively. All mothers received both magnesium sulfate and betamethasone before delivery. The median cumulative dose of indomethacin was 225 mg. The median interval from last dose of indomethacin until delivery was 12 hours. There were no significant differences between the groups in the incidence of necrotizing enterocolitis (odds ratio, 1.12; 95% confidence interval, 0.31-3.84), grade III/IV intraventricular hemorrhage (odds ratio, 0.37; 95% confidence interval, 0.10-1.19), patent ductus arteriosus (odds ratio, 0.85; 95% confidence interval, 0.44-1.64), bronchopulmonary dysplasia (odds ratio, 0.97; 95% confidence interval, 0.49-1.91), pulmonary hypertension (odds ratio, 0.49; 95% confidence interval, 0. 02-4.80), anuria (odds ration, 1.21; 95% confidence interval, 0.22-6. 01), thrombocytopenia (odds ratio, 1.14; 95% confidence interval, 0. 53-2.42), sepsis (odds ratio, 1.21; 95% confidence interval, 0.22-6. 01), or neonatal death (odds ratio, 1.34; 95% confidence interval, 0. 55-3.25). CONCLUSION: Maternal indomethacin exposure immediately before delivery was not associated with increased neonatal complications for infants delivered between 24 and 32 weeks' gestation.

Effect of hemodialysis on serum progesterone level in pregnant women.

The objective of this study is to evaluate the effect of chronic hemodialysis on serum progesterone level in pregnancy. Serum progesterone levels were measured predialysis and postdialysis using the radioimmunoassay technique in seven gravid women with renal failure requiring hemodialysis. Uterine contractions were measured before and after hemodialysis using home uterine activity monitoring (HUAM) in two patients. Thirty-three paired serum samples were obtained between 14 and 39 weeks' gestation. The mean change in serum progesterone level postdialysis throughout pregnancy ranged from -52.0% to +8.7% for each individual patient. The change in serum progesterone level was unrelated to gestational age. The woman experiencing the most significant decrease in serum progesterone level with dialysis continued her pregnancy to greater than 39 weeks. No significant increase in uterine contraction frequency was noted on HUAM postdialysis (P = 0.22), although both monitored patients experienced a small increase in serum progesterone levels. In conclusion, serum progesterone values showed a variable patient-specific response when measured predialysis and postdialysis in pregnancies complicated by renal failure. There was no significant increase in uterine activity noted postdialysis. Progesterone withdrawal does not appear to explain the increased frequency of preterm delivery in women after dialysis.

The importance of early weight gain in the intrauterine growth and birth weight of twins.

OBJECTIVE: It was our objective to evaluate the association between early maternal weight gain (before 20 weeks), midpregnancy weight gain (20-28 weeks), and late pregnancy weight gain (28 weeks to birth) with fetal growth and birth weight in twins. STUDY DESIGN: This historic cohort study was based on 1564 births of live twins >/=28 weeks' gestation from Baltimore, Maryland, Miami, Florida, Charleston, South Carolina, and Ann Arbor, Michigan. RESULTS: Early fetal growth was affected only by smoking and chorionicity. Factors in models of both mid and late fetal growth included maternal age, pregravid weight, parity, rates of early pregnancy and midpregnancy maternal weight gain, smoking, and pre-eclampsia. Increased midpregnancy fetal growth was associated with early maternal weight gain (10.91 g/wk per pound per week) and midpregnancy maternal weight gain (15.89 g/wk per pound per week). Increased late fetal growth was associated with early maternal weight gain (16.86 g/wk per pound per week) and midpregnancy maternal weight gain (23.88 g/wk per pound per week). Increased birth weight was associated with early (283.02 g per pound per week), mid (163.58 g per pound per week), and late (69.76 g per pound per week) maternal weight gains. CONCLUSIONS: These findings confirm the importance of early maternal weight gain in twin fetal growth and birth weight.

Drug therapy in the nursing mother.

The benefits of breast-feeding on newborn and infant health and for the maternal-infant relationship are well established. It is a failing of health care providers that breast-feeding is too frequently interrupted because of unfounded concerns over the potential adverse effects of concurrent drug therapy in the nursing mother. An overwhelming minority of medications are contraindicated during lactation, while the vast majority are considered either safe to use or the risk versus benefit considerations clearly favor use with continuation of breast-feeding. For those drugs that may pose a potential concern to the newborn, there are practical suggestions and precautions that can be taken to minimize risk. These include such interventions as selection of alternative effective drug regimens with safer profiles in breast-feeding, timing of drug dosing to minimize accumulation in the breast milk, surveillance for newborn or infant symptomatology that may be a sign of toxicity, or even the determination of drug levels in the infant's circulation. With a commitment to the advantages of breast-feeding and the information contained both herein and elsewhere regarding the interaction of medical therapy, pharmacology, and lactation, it is hoped that the health care provider will be empowered both to encourage and counsel more effectively the parturient who wishes to breast-feed but is concerned about ongoing drug therapy during lactation.

Correlation of antepartum uterine activity and cervical change in twin gestation.

OBJECTIVE: To determine the correlation between quantitative measurements of antepartum uterine activity and cervical change twin gestations. METHODS: Forty women from our Twin Clinic constituted the study group. Participants had a cervical examination each week between 20 and 37 weeks gestation and a cervical score (CS) was calculated as follows: CS = cervical length (cms)-cervical dilation (cms) at the internal os. The women also performed blinded home uterine activity monitoring (HUAM) for a mean of 7.0 + 3.0 hrs/wk (+SD). Uterine activity was expressed as mean number of contractions/hour/week gestation based on the average of three independent reviewers. CS was determined by a single clinician unaware of the HUAM recordings. A significant change in the CS was defined as a reduction of at least 0.5 from the preceding week. Correlation coefficients were used to determine the association between uterine activity and change in the cervical score. RESULTS: Twin pregnancy was characterized by a rise from 0.2 + .03 contractions/hr at 20 weeks to 3.2 + 2.4 contractions/hr at 37 weeks gestation. CS fell from a mean of 2.6 + 0.2 at 20 weeks to -2.1 + 0.9 at 37 weeks gestation. There was a significant negative correlation (-0.317, p < .0001) between increasing uterine activity and decreasing CS. There were significantly more (p < .002) contractions during the 7 days preceding a significant reduction in CS (3.3 + 3.5 contractions/hr) than when the CS was unchanged (1.6 +/- 1.5 contractions/hr). CONCLUSIONS: In twin gestations, an increasing frequency of uterine contractions is strongly correlated with quantifiable cervical change between 20-37 weeks gestation. Persistent daytime contraction frequencies of > 3/hr represent a risk factor for cervical dilation and/or effacement.

Eclampsia as a possible risk factor for persistent trophoblastic disease.

Twenty cases of hydatidiform mole complicated by eclampsia with adequate postevacuation follow-up are identified in a review of the literature since 1866. The clinical presentation of each of these patients is reviewed with particular attention to the existence of known risk factors for persistent trophoblastic disease. After excluding 3 women with coexisting fetus and 2 others who were treated initially with a total abdominal hysterectomy, it was discovered that 14 of the remaining 15 women developed persistent trophoblastic disease. This frequency of persistent trophoblastic disease is greater than can be explained based on previously described risk factors and suggests that the occurrence of eclampsia may be an independent risk factor for persistent trophoblastic disease.

Association of eclampsia and hydatidiform mole: case report and review of the literature.

A patient with a hydatidiform mole complicated by eclampsia is presented. The findings from 57 other cases discovered in a review of the literature since 1866 are summarized to define the clinical characteristics of women experiencing eclampsia as a manifestation of their hydatidiform mole. Eclampsia complicating a molar pregnancy is generally preceded by typical preeclamptic symptomatology and uniformly by severely elevated blood pressure. Neurological or visual symptoms also commonly warn of impending eclampsia. Although the reported cases of eclampsia complicating molar pregnancies are rare, this risk argues for the liberal use of prophylactic antiseizure medication when caring for women with a hydatidiform mole and hypertension, neurological complaints, or other preeclamptic symptoms.