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Summary Regression models for the analysis of ordered categorical variables are discussed with particular reference to the logistic model. Maximum likelihood estimation procedures are established for three common sampling plans including the case where sampling is conditional on the ordered variable. This was previously not available. The use of these models in discrimination is discussed and an example given. An original method for the establishment of rating scales based on a coarse direct assessment and related variables is introduced. Mention is made of some difficulties in the application of the models and of their potential use for the analysis of designed experiments with ordered response variables.

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Serial changes in serum uric acid concentrations have been studied in a group of healthy women before conception, at regular intervals throughout pregnancy and finally 12 weeks after delivery. Compared with pre-pregnancy values uric acid concentrations decreased significantly by 8 weeks gestation and this reduced level was maintained until about 24 weeks. Thereafter the concentrations increased such that by term they were greater than the pre-pregnancy values in the majority of patients and remained elevated until a t least 12 weeks after delivery. If clinical management during the second half of pregnancy is to be based on increases in serum uric acid concentrations then such increases will have to be carefully interpreted against the background of rising concentrations which occur as part of the physiological response t o normal pregnancy.Modern clinicians rely increasingly on laboratory tests for the management of patients; for some the stage has been reached when deviation from an accepted range of laboratory values is in itself sufficient reason to justify treatment. The principle is not intrinsically unreasonable but clinical management based solely, or even largely, on such tests implies a confidence in the 'normality' of any given range of laboratory values that is seldom justified.During pregnancy progressive maternal physiological adaptations occur and many biochemical measurements deviate conspicuously from the normal range for males and nonpregnant females. Laboratory ranges specific to pregnancy need to be defined and ideally would be determined in healthy women having uncomplicated pregnancies resulting in the birth of live healthy children; such data are relatively scarce.This paper describes the changes in serum uric acid concentrations throughout normal pregnancy and reports two clinically important aspects. First the values decrease significantly below non-pregnant levels by 8 weeks gestation; second serum uric acid concentrations are not only increased above non-pregnant values by term in many women but remain elevated for as long as 12 weeks after delivery. Such postpartum values should not therefore be used as representative of non-pregnant concentrations. Patients and methods PatientsThirty-one healthy women have been studied; the mean age was 28 (range 23-37) years and each was without any adverse medical, surgical or obstetric history. In five of the women uric acid determinations were repeated during a subsequent pregnancy so that data were obtained from a total of 36 pregnancies. Nine women were primigravidae and 27 were multiparae of whom five had had a previous spontaneous abortion and 22 a successful pregnancy. During the time of this study none of the patients developed medical or obstetric complications or required pharmacological agents including salicylates; all gave birth to live, healthy infants. 128

IntroductionSerial studies were designed to characterize changes in osmoregulation throughout gestation. Eight women underwent a 2-h infusion of hypertonic saline before conception, during gestational weeks 5-8, 10-12, and 28-33, and then 10-12 wk postpartum. Basal plasma osmolality (P.,6.l,1) was already significantly decreased by 5-8 wk (P < 0.001) and remained 10 mosmol' kg-' below nonpregnant values throughout pregnancy. The apparent threshold for AVP release (defined as the abscissal intercept of the regression line relating plasma AVP IPAvPI to P..,) was also decreased significantly throughout gestation, as was the osmotic threshold for thirst (derived from analogue scales relating desire to drink to P~..,,1). The decrement in osmotic thirst threshold appeared to precede that for AVP release, and consistent with this 24-h urine volumes were significantly greater at 5-8 wk gestation (P < 0.05). The slopes of each regression equation defining PAVP vs. P.., (whose r values ranged from 0.79 to 0.99), very reproducible before and after pregnancy, were similar at 5-8 and 10-12 wk, but were markedly reduced in the third trimester (P < 0.001). These volunteers had randomly undergone an additional infusion before conception (both tests in the luteal phase of the menstrual cycle) when 10,000 IU of human chorionic gonadotrophin (hCG) had been given intramuscularly over a 5-d period.Serum hCG values between 0.2 and 3.3 U. ml-' were lower than usually seen in pregnancy, but the osmotic thresholds for AVP release and thirst decreased by 3 and 4 mosmol* kg-l, respectively (P < 0.05). Finally we studied a patient with a molar pregnancy in whom thresholds for hormone release and thirst were both decreased to values resembling normal gestation and remained so for -6 wk postevacuation, only normalizing when hCG had virtually disappeared from her serum. In contrast, thresholds increased within the first two puerperal weeks in two women with normal pregnancies. These data demonstrate (a) osmotic thresholds for both AVP release and thirst decrease within the very first gestational weeks; (b) Women wishing to conceive were serially tested. Before conception they were studied twice, once in the basal state and again after having been pretreated with human chorionic gonadotrophin (hCG). They were then retested during gestational weeks 5-8, 10-12, and 28-33, and again postpartum. Also studied was a single patient with a hydatiform mole.The results demonstrate that the thresholds for AVP release and thirst decline early in the first trimester and explain the rapid decline in body tonicity during the initial months of gestation. Observations made when testing the patient with a molar pregnancy demonstrate that the osmoregulatory alterations of gestation do not require the presence of the fetus. Furthermore, the results produced by hCG administration, combined with those observed in the woman whose hydatiform mole was evacuated, suggest that hCG may be involved in the decrements in the osmotic thresholds that occur in pr...