Repeated antenatal corticosteroid treatments adversely affect neural transmission time and auditory thresholds in laboratory rats.

Antenatal corticosteroid (AC) treatment is given to pregnant women at risk for preterm birth to reduce infant morbidity and mortality by enhancing lung and brain maturation. However, there is no accepted regimen on how frequently AC treatments should be given and some studies found that repeated AC treatments can cause growth retardation and brain damage. Our goal was to assess the dose-dependent effects of repeated AC treatment and estimate the critical number of AC courses to cause harmful effects on the auditory brainstem response (ABR), a sensitive measure of brain development, neural transmission and hearing loss. We hypothesized that repeated AC treatment would have harmful effects on the offspring's ABRs and growth only if more than 3 AC treatment courses were given. To test this hypothesis, pregnant Wistar rats were given either a high regimen of AC (HAC), a moderate regimen (MAC), a low regimen (LAC), or saline (SAL). An untreated control (CON) group was also used. Simulating the clinical condition, the HAC dams received 0.2mg/kg Betamethasone (IM) twice daily for 6 days during gestation days (GD) 17-22. The MAC dams received 3 days of AC treatment followed by 3 days of saline treatment on GD 17-19 and GD 20-22, respectively. The LAC dams received 1 day of AC treatment followed by 5 days of saline treatment on GD 17 and GD 18-22, respectively. The SAL dams received 6 days of saline treatment from GD 17 to 22 (twice daily, isovolumetric to the HAC injections, IM). The offspring were ABR-tested on postnatal day 24. Results indicated that the ABR's P4 latencies (neural transmission time) were significantly prolonged (worse) in the HAC pups and that ABR's thresholds were significantly elevated (worse) in the HAC and MAC pups when compared to the CON pups. The HAC and MAC pups were also growth retarded and had higher postnatal mortality than the CON pups. The SAL and LAC pups showed little or no adverse effects. In conclusion, repeated AC treatment had harmful effects on the rat offspring's ABRs, postnatal growth and survival. The prolonged ABR latencies reflect slowed neural transmission times along the auditory nerve and brainstem auditory pathway. The elevated ABR thresholds reflect hearing deficits. We concluded that repeated AC treatment can have harmful neurological, sensory and developmental effects on the rat offspring. These effects should be considered when weighing the benefits and risks of repeated AC treatment and when monitoring and managing the prenatally exposed child for possible adverse effects.

Magnesium prevents seizure-induced reduction in excitatory amino acid receptor (kainate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) binding in pregnant rat brain.

OBJECTIVE: Our purpose was to evaluate the effect of seizures on kainate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor binding in maternal rat brain and whether maternal peripheral administration of magnesium sulfate can decrease this effect. STUDY DESIGN: Rats were implanted with a bipolar electrode into the hippocampus. One week of recovery was allowed before breeding. Pregnant rats were randomly assigned to 1 of 4 groups, as follows: group 1, sodium chloride and no seizures (n = 5); group 2, magnesium sulfate and no seizures (n = 4); group 3, sodium chloride and seizures (n = 8); and group 4, magnesium sulfate and seizures (n = 9). Doses of sodium chloride or magnesium sulfate were administered every 20 minutes for 4 hours to all rats on gestational days 9, 11, 13, 15, 17, and 19, followed by seizure induction (groups 3 and 4). On gestational day 20, rats were perfused, brains were dissected, and cryostat sections were taken, labeled in vitro, and placed on Hyperfilm for 4 weeks. The ligands used included kainate receptor agonist and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor agonist and antagonist. Optical density measurements of binding in 15 brain regions on each section were evaluated by 1- and 2-way analysis of variance. RESULTS: Seizure activity was associated with decreased alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor binding of its agonist in pregnant rat brains (seizure effect, 25.9 +/- 3.2 and 92.6 +/- 3.4 fmol/mg tissue in hindbrain and forebrain, respectively; no seizure effect, 44.5 +/- 4.7 and 110. 7 +/- 5.0 fmol/mg tissue in hindbrain and forebrain, respectively; P <.01). Magnesium administration was associated with increased binding of tritiated alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (magnesium effect, 44.9 +/- 4.2 and 110.4 +/- 4.5 fmol/mg tissue in hindbrain and forebrain, respectively; sodium chloride effect, 25.5 +/- 3.7 and 92.9 +/- 4.0 fmol/mg tissue in hindbrain and forebrain, respectively; P <.01). The same trend was seen with the kainate receptor in the hippocampus and hypothalamus, with a significant interaction effect between seizure and magnesium (P <.05). CONCLUSIONS: The mechanism for maternal rat brain injury resulting from seizure activity may be, at least in part, associated with alteration in the function of excitatory amino acid receptors. Administration of magnesium sulfate can counteract this effect and may reduce resultant maternal brain damage.

The effect of magnesium sulfate on fetal heart rate parameters: A randomized, placebo-controlled trial.

OBJECTIVE: We sought to determine the effect of magnesium sulfate on fetal heart rate baseline value, variability, and acceleration-deceleration pattern. STUDY DESIGN: Normal, nonlaboring pregnant patients at >30 weeks' gestation were recruited. Baseline fetal heart rate monitoring for 1 hour was performed. After an 800-kcal meal, patients were randomized to receive either an intravenous loading dose of 6 g of magnesium sulfate in 100 mL of isotonic sodium chloride solution or 100 mL of isotonic sodium chloride solution alone. Subsequently, patients in the magnesium sulfate group received a 2-g/h intravenous infusion for 3 hours at a rate of 125 mL/h. Patients randomized to the sodium chloride solution group received a sodium chloride solution infusion at a similar rate (unlabeled intravenous bags). Maternal blood was drawn at 0, 1, and 3 hours for determination of total and ionized magnesium and calcium, electrolyte, and glucose levels. One hour of fetal heart rate monitoring was repeated at 1 and 3 hours of infusion. Tracings were interpreted without identifiers (of time or group) by using the National Institute of Child Health and Human Development fetal heart rate monitoring guidelines. RESULTS: Magnesium sulfate administration resulted in decreased fetal heart rate baseline values and variability in the third hour. The fetal heart rate baseline value was 134.4 +/- 6.3 versus 136.6 +/- 6.4 beats/min before infusion (P >.05), 134.4 +/- 7.1 versus 135.1 +/- 6. 6 beats/min in the first hour (P >.05), and 134.6 +/- 7.1 versus 132. 3 +/- 7.6 beats/min in the third hour (P <.05) in the sodium chloride solution group versus the magnesium sulfate group, respectively. Fetal heart rate variability (grades 1-5) was 2.75 +/- 0.33 versus 2.82 +/- 0.29 before infusion (P >.05), 2.81 +/- 0.30 versus 2.84 +/- 0.28 in the first hour (P >.05), and 2.71 +/- 0.52 versus 2.67 +/- 0.36 in the third hour in the sodium chloride solution group versus the magnesium sulfate group, respectively (P <. 05). Magnesium sulfate blocked the positive correlation between gestational age and number of accelerations found in control subjects. No significant decelerations were identified. CONCLUSIONS: Prolonged administration of magnesium sulfate was associated with decreased fetal heart rate baseline values and variability. Given the small magnitude of these changes, the clinical significance of these findings is questionable. Magnesium sulfate inhibition of the increasing number of accelerations with gestational age needs to be considered when fetal well-being is assessed.

How do physicians define "light," "moderate," and "heavy" drinking?

Although widely used, terms associated with consumption of alcohol--such as "light," "moderate," and "heavy"--are unstandardized. Physicians conveying health messages using these terms therefore may impart confusing information to their patients or to other physicians. As an initial attempt to assess if informal standardization exists for these terms, the present study surveyed physicians for their definitions of such terms. Physicians operationally defined "light" drinking as 1.2 drinks/day, "moderate" drinking as 2.2 drinks/day, and "heavy" drinking as 3.5 drinks/day. Abusive drinking was defined as 5.4 drinks/day. There was considerable agreement for these operational definitions, indicating there is indeed an informal consensus among physicians as to what they mean by these terms. Gender and age did not influence these definitions, but self-reported drinking on the part of physicians was a factor. We also asked physicians for their opinions regarding the effects of "light," "moderate," and "heavy" drinking on health in general and specifically on health-related implications for pregnant women, and whether they felt their patients shared these beliefs.

The effect of capitated and fee-for-service remuneration on physician decision making in gynecology.

OBJECTIVE: To evaluate the variations in physician behavior leading to performance of gynecologic surgical procedures related to fee-for-service and capitation reimbursement systems. METHODS: This study compared the physician practice utilization of surgical services for fee-for-service and capitated contract reimbursement systems within a gynecology clinic. Attending gynecologists were reimbursed on a fee-for-service basis for all surgical services performed during a 6-month interval; subsequently, the same physicians were reimbursed on a capitated basis for 6 months and received a fixed payment for the clinical and surgical services provided. RESULTS: Three thousand seven hundred eighty consecutive outpatient gynecology visits were evaluated at the university gynecology clinic during 1994. We found a 15% overall decrease in the number of surgical procedures that were performed during the capitated reimbursement period compared with the fee-for-service time interval. The procedure most responsible for the reduction of surgical services was elective sterilization by laparoscopy, which underwent a statistically significant decrease (P < .01). CONCLUSION: The remuneration system in our review seemed to affect physician decision making for only the most elective procedures, whereas physicians maintained similar practice patterns for more severe conditions. Fee-for-service seems to encourage, whereas capitation seems to discourage, gynecologist from performing elective procedures.

Hon v. Stroh Brewery Company: what do we mean by "moderate" and "heavy" drinking?

Although widely used, drinking terms such as "light,"' "moderate," and "heavy" are unstandardized and, as a result, public health messages using these terms may convey confusing information. As an initial attempt in providing such standardization, the present study surveyed public definitions for these terms. "Light" drinking was operationally defined as 1.4-2.4 drinks/day; "moderate" drinking was defined as 2.5-3.6 drinks/day; and "heavy" drinking was defined as 3.7 drinks/day and above. These ranges, however, were dependent on the respondent's gender, age, socioeconomic status, and especially the respondent's self-reported tolerance. Males had a higher threshold of consumption for "moderate" and "heavy" drinking than women. Older respondents likewise assigned a higher threshold for these terms than younger respondents. As respondent income increased, the threshold for "heavy" drinking decreased. The heaviest drinkers had a higher threshold for assigning the "heavy" label than did any other group. Ethnicity did not significantly affect these ranges, and religion only affected the threshold for "heavy" drinking. Because reseachers ultimately rely on terms such as "moderate" or ":heavy" to communicate their findings to colleagues and the public, it would seem apposite for them to agree on operational definitions for such terms. It would also seem appropriate to consider the operational definitions the public uses when referring to these terms to promote credibility of research findings and appropriate changes in behavior.

Attenuation of the magnitude of suckling-induced prolactin release with advancing lactation: mechanisms.

To study why suckling-induced plasma prolactin levels decline in magnitude with advancing lactation, we examined prolactin release in lactating rats following suckling and pharmacologic manipulations during early, mid- and late lactation. On day 2 of lactation, litters were adjusted to 8 pups. On day 3, dams were implanted with an atrial catheter and experiments were conducted on lactation days 5, 11 and 17. To examine suckling-induced prolactin release, pups were removed at 0800 h, an extension was attached to the catheter at 1100 h, and pups returned to dams at 1200 h. Blood samples were obtained before, and at 10, 30, 60, 90 and 120 min after suckling started. Prolactin responses to sulpiride and thyrotropin releasing hormone (TRH) administration were studied in lactating rats separated from their litters for 4 hours. Blood samples were obtained before, and at 10, 30, 60 and 90 min after sulpiride (10 or 40 micrograms/kg BW) and 5, 10, 20 and 30 min after TRH (1 or 4 micrograms/kg BW) in rats pretreated with sulpiride. Prolactin release in response to suckling, administration of sulpiride or sulpiride and TRH diminished as lactation advanced. From these results, we conclude that refractoriness in anterior pituitary lactrotropes to prolactin-releasing stimuli is at least partially responsible for the decline in suckling-induced prolactin release with advancing lactation.

"Population" characteristics of birthweight in an animal model of alcohol-related developmental effects.

A retrospective analysis of a large database of maternal and litter variables in rats collected over several years evaluated the robustness of fetal alcohol effects on birthweight. Pregnant rats were fed a liquid diet in which 35% of the calories were derived from alcohol. Control dams were pairfed an isocaloric liquid diet or were fed lab chow ad lib. Alcohol exposure produced large, highly significant, and reliable decreases in birthweight of male and female pups. Multiple regression analyses indicated that alcohol exposure per se, much more than restricted caloric intake alone, caused these effects. Litters of pairfed dams weighed less than chowfed controls but the effects were less consistent, varying with season and requiring more litters to discriminate the effects of restricted caloric intake. Power analyses indicated that 7 to 12 litters per group are needed for detecting a statistically significant reduction in birthweight due to prenatal alcohol exposure, even with single pups selected at random from each litter. Alcohol-exposed pups also weighed consistently and significantly less than both the chowfed and pairfed pups, whereas differences between chowfed and pairfed groups were much smaller and inconsistent. The results imply that decreased birthweight is a consistent characteristic of prenatal alcohol exposure.

Acute alcohol infusion does not alter plasma gonadotropins or prolactin in ovariectomized rats.

We examined the effects of acute alcohol on basal plasma FSH, LH, and prolactin in ovariectomized rats. Alcohol infusion and blood sampling were done via an indwelling atrial catheter. Blood samples for alcohol and hormone determinations were collected before, and 5 to 120 min after completion of saline (control) or alcohol in saline (experimental) infusion. Plasma follicle-stimulating hormone, luteinizing hormone, and prolactin were not altered during the 2-hr period. Peak blood alcohol concentrations achieved following 1.0- and 2.0-g/kg body weight of alcohol doses were approximately equal to, and twice, the legal human intoxication levels, respectively. Alcohol clearance rates from blood for the two groups were: 130 +/- 3 mg/kg/hr for the 1.0-g/kg body weight group and 151 +/- 3 mg/kg/hr for the 2.0-g/kg body weight group. These results show that acute alcohol does not affect basal gonadotropins and prolactin secretion in ovariectomized rats.