PIERS proteinuria: relationship with adverse maternal and perinatal outcome.

OBJECTIVE: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes. METHODS: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessments. RESULTS: More women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30 g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome. CONCLUSION: The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.

Fetal, infant, and childhood growth and adult blood pressure: a longitudinal study from birth to 22 years of age.

BACKGROUND: People who are small at birth tend to have higher blood pressure in later life. However, it is not clear whether it is fetal growth restriction or the accelerated postnatal growth that often follows it that leads to higher blood pressure. METHODS AND RESULTS: We studied blood pressure in 346 British men and women aged 22 years whose size had been measured at birth and for the first 10 years of life. Their childhood growth was characterized using a conditional method that, free from the effect of regression to the mean, estimated catch-up growth. People who had been small at birth but who gained weight rapidly during early childhood (1 to 5 years) had the highest adult blood pressures. Systolic pressure increased by 1.3 mm Hg (95% CI, 0.3 to 2.3) for every standard deviation score decrease in birth weight and, independently, increased by 1.6 mm Hg (95% CI, 0.6 to 2.7) for every standard deviation score increase in early childhood weight gain. Adjustment for adult body mass index attenuated the effect of early childhood weight gain but not of birth weight. Relationships were smaller for diastolic pressure. Weight gain in the first year of life did not influence adult blood pressure. CONCLUSIONS: Part of the risk of adult hypertension is set in fetal life. Accelerated weight gain in early childhood adds to this risk, which is partly mediated through the prediction of adult fatness. The primary prevention of hypertension may depend on strategies that promote fetal growth and reduce childhood obesity.

Implications of new diagnostic criteria for abnormal glucose homeostasis in women with previous gestational diabetes.

OBJECTIVE: To determine the consequences of applying revised American Diabetes Association (ADA) (1997) and World Health Organization (WHO) (1998) recommendations for the classification of glucose intolerance in women with previous gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: There were 192 women with previous GDM who took an oral glucose tolerance test (OGTT) 1-86 months after delivery and were classified by WHO (1985), ADA (1997, fasting glucose), and revised WHO (1998) guidelines. RESULTS: Among the 165 women without a preexisting diagnosis of diabetes, WHO-1985 and ADA-1997 provided similar estimates of diabetes prevalence (13.3% vs. 11.5%) but widely differing estimates of impaired glucose homeostasis (31.5% impaired glucose tolerance [IGT] by WHO-1985 vs. 10.9% impaired fasting glucose by ADA-1997 criteria). Overall, 56 women (34%) showed a classification discrepancy between WHO-1985 and ADA-1997 criteria, including 44 with normal fasting glucose by ADA-1997 criteria, but abnormal 2-h glucose by WHO-1985 criteria (40 IGT, 4 diabetes). The cardiovascular risk profile of these women was more favorable than that of 18 women with impaired fasting glucose. WHO-1998 recommendations reproduced ADA-1997 findings when used as a fasting screen, but behaved similarly to WHO-1985 criteria when 2-h glucose values were also analyzed. CONCLUSIONS: All criteria produced similar estimates of diabetes prevalence. However, analyses based on a single fasting glucose screen (and a threshold of 6.1 mmol/l) failed to identify 60% of women with abnormal 2-h glucose levels. Screening women with previous GDM (and by analogy, other groups at high risk of diabetes) with a single fasting glucose has low sensitivity for the detection of abnormal glucose tolerance. Recent guidelines recommending this approach require reevaluation.

Blood pressure in four and five-year-old children: the effects of environment and other factors in it's measurement--the Brompton study.

Systolic blood pressure was measured on a total of 1855 occasions in 1307 children aged four and five years, and compared with values obtained since birth in the same children. There was a rapid rise in blood pressure in the first month of life. The mean blood pressure then only rose from 93 mmHg at six months to 98 mmHg at five years. The 95th percentile was 113 to 114 mmHg over this period. In children aged four and five years, over the ranges studied, blood pressure was not importantly affected by place of measurement, time of day, time since previous meal, or ambient temperature. However, blood pressure was approximately 1.6 mmHg higher in winter than in summer (P less than 0.01). Nevertheless, it is unlikely that these factors are of significance when making clinical measurements. Blood pressure was correlated with weight at all ages. Between the ages of four and five years, the index, weight/height 1.70 was the best function of adiposity tested that was independent of age between four and five years. It is suggested that this or the Quetelet Index (weight/height2) are suitable indices for adjusting blood pressure for body build in children aged four and five years.

The British Hypertension Society protocol for the evaluation of automated and semi-automated blood pressure measuring devices with special reference to ambulatory systems.

With the increasing manufacture of expensive systems for the measurement of ambulatory blood pressure there is a need for potential purchasers to be able to satisfy themselves that the systems have been evaluated according to agreed criteria. The British Hypertension Society has, therefore, drawn up a protocol of requirements for the evaluation of these devices. This protocol incorporates many features of the American National Standard for Non-Automated Sphygmomanometers but includes many additional features, such as strict criteria for observer training, interdevice variability testing before and after a month of ambulatory use, and a new system of analysis which permits the test system to be graded. It is recommended that manufacturers of ambulatory blood pressure measuring devices should obtain an unbiased evaluation according to a recognized standard before a device is marketed.

Systolic blood pressure in a population of infants in the first year of life: the Brompton study.

Systolic blood pressure (BP) was measured by the Doppler technique and random zero sphygmomanometer in a sample of infants between the ages of 4 days (n = 1,740) and 1 year (n = 1,338). Mean systolic BP rose from 76 mm Hg at age 4 days to 96 mm Hg at age 6 weeks in babies awake, and showed little further variation at 6 months and 1 year. The BP was approximately 6 mm Hg higher in babies awake than asleep. Blood pressure was nearly normally distributed at all ages and the 95th percentile for BP of babies awake was 95 mm Hg at 4 days and 113 mm Hg between 6 weeks and 1 year. A comparison of intra-arterial and Doppler BP confirmed that both inflation bag length and cuff width are important for accurate measurement.

Sequential 22-hour profiles of breathing patterns and heart rate in 110 full-term infants during their first 6 months of life.

Sequential recordings (total number 365, mean duration 22 hours) of ECG and abdominal wall movement were obtained from 110 full-term infants up to 6 months of age. The longest pause in breathing movement per recording (maximum 21.6 seconds) decreased in duration over the first 2 weeks of life (P less than .005). Pauses greater than 18.0 seconds were not detected after seven days. The spread of values for pauses greater than or equal to 3.6 seconds duration was widest during the first 2 weeks, and their number decreased with age (P less than .001). Periodic breathing, detected in 69% to 80% of infants in all age groups, showed decreasing trends with age in total duration and maximum length of episode (P less than .005 for both). The spread of values was widest during the first 2 weeks (range for total duration 0 to 4.7 hours) and decreased with age. The mean respiratory rate during regular breathing decreased after 4 weeks (P less than .001). The spread of values was widest during the first 2 weeks and decreased with age. Birth weight was positively correlated with mean respiratory rate during the first three days of life (r = +.64, P less than .001). The mean heart rate during regular breathing increased during the first 15 days (P less than .001) and then decreased after 4 weeks (P less than .001). Higher mean heart rates were found in male infants (P less than .01).

Titration of antiplatelet treatment in pregnant women at risk of preeclampsia.

We recruited 111 patients who were considered to be at significantly increased risk of preeclampsia on the basis of previous obstetric history or preexisting medical disorders. All patients were treated with low dose aspirin (75 mg/day) from the first occasion the patient attended the antenatal clinic, regardless of gestational age. If the maternal mean platelet volume (MPV) increased significantly (by > 0.8 fl) from the baseline, antiplatelet treatment was increased. Five pregnancies were lost during the second trimester and 106 of the treated patients had live infants. The incidence of neonatal death (3/106 infants) was much lower than in the previous pregnancies in these patients (32/134 infants). Patients who were treated from the first trimester of pregnancy (group A, 89 patients) did substantially better than those treated from the second trimester (group B, 17 patients) as assessed by the incidence of pre-eclampsia or intrauterine growth restriction (IUGR), gestational age and birthweight at delivery. These data suggest that longitudinal monitoring of the MPV may identify the women who could benefit from increased antiplatelet treatment, and that antiplatelet treatment may be more effective when initiated in the first trimester rather than later in pregnancy.

Discordant blood flow velocity waveforms in left and right brachial arteries in growth-retarded fetuses.

OBJECTIVE: To determine if the increase in cerebral blood flow ("brain-sparing" effect) with fetal hypoxemia is associated with discordant hemodynamics in the upper extremities. METHODS: We studied 12 fetuses with severe growth retardation, absent or reverse end-diastolic blood flow in the umbilical artery, and low pulsatility index (PI) in the middle cerebral artery, and 12 appropriately grown control fetuses with normal fetoplacental Doppler studies. The right and left brachial arteries were identified by high-resolution color Doppler ultrasonography, and the PI was measured in each brachial artery. RESULTS: All growth-retarded fetuses had lower impedance indices in the right than in the left brachial artery (mean delta PI 1.0, 95% confidence interval [CI] 0.7-1.3, P < .001). No differences in the brachial artery impedance indices were found in control fetuses matched for gestational age (mean delta PI 0.0, 95% CI -0.2 to 0.2). CONCLUSIONS: Left and right brachial artery blood flow velocity waveforms are discordant in fetuses with growth retardation and cerebral vasodilation. Because the right arm receives its blood supply from the same source as the brain (brachiocephalic artery) and given the proximity of the left subclavian artery to the ductus arteriosus, we speculate that this might be the result of increased blood flow into the brachiocephalic circulation and/or functional differences in the distribution of left and right ventricular output within the aortic arch in response to fetal hypoxemia.

Impaired vasoconstriction in pregnancy-induced hypertension assessed using doppler fluximetry.

OBJECTIVE: To determine whether there is a difference in peripheral vascular reactivity between normal women and those with pregnancy-induced hypertension. METHODS: Capillary blood flow (flux) was recorded in the skin over the ankle in 26 pregnant women with pregnancy-induced hypertension at term. Twelve of these women had proteinuria, and 14 were nonproteinuric. Leg lowering was used to activate the venoarteriolar reflex, and the resultant change in flux, expressed as a percentage change from the baseline, was used as an index of vascular reactivity. The results were compared with those of a control group comprising 23 matched normotensive women. The study was repeated on all of the women after delivery. RESULTS: Women with hypertension showed a median (range) increase in flux of +24.4% (-15.5% to +151.1%), significantly different from controls: -39.3% (-80.9% to -4.3%, P <.001). This difference persisted regardless of the presence or absence of proteinuria. Responses in women with pregnancy-induced hypertension were significantly different after delivery (median -60.7%; range -158.5% to -19.5%, P <.001) when compared with predelivery responses. Similar changes as a result of delivery were seen in women with proteinuric (medians +25.9% and -57. 9%, P <.002) and nonproteinuric (medians +7.8% and -62.8%, P <.001) hypertension but not in controls. Postdelivery responses in women with hypertension were no different from those of controls. CONCLUSION: Women with pregnancy-induced hypertension have abnormal cutaneous vascular reactivity that returns to normal after delivery.

Hypertension in pregnancy: which method of blood pressure measurement is most predictive of outcome?

OBJECTIVE: To determine the clinical effectiveness of blood pressure (BP) measurement using conventional sphygmomanometry in the antenatal clinic and obstetric day unit compared with automated BP monitoring at home. METHODS: The study population consisted of 109 nulliparous white women with BPs of at least 140 or 90 mmHg at the antenatal clinic after 20 weeks' gestation, who underwent obstetric day unit and 24-hour automated BP monitoring on the same day. Automated measurement was obtained every half hour for 24 hours using a commercially available device that had been previously validated in pregnancy. RESULTS: At the traditional BP cutoff point (140/90 mmHg), the relative risk for subsequent development of adverse obstetric outcome was greatest for automated BP measurement: The relationships between outcome and automated diastolic BP were all statistically significant: proteinuria (P = .034), preterm delivery (P < .001), birth weight below the tenth percentile (P = .001), admission to the special care neonatal unit (P = .001), and cesarean delivery (P = .007). CONCLUSION: Automated BP measurement appears to improve the identification of patients who are at high risk of poor obstetric outcome. Automated BP measurement is worthy of further evaluation as an antenatal screening and diagnostic test.

Diurnal blood pressure difference in the assessment of preeclampsia.

OBJECTIVE: To evaluate diurnal variation in blood pressure (BP) in normal gravidas and those with preeclampsia, using ambulatory BP monitoring. METHODS: A cross-sectional comparative observational study was performed in three teaching hospital maternity units. Twenty-four normotensive and 24 preeclamptic women who were similar in age, weight, and mean duration of gestation (35 weeks) were studied. Diurnal variation and BP measurement were assessed using ambulatory BP monitors validated for use in pregnancy and for which normal reference ranges for pregnancy have been derived. RESULTS: At night, the BP fall was less in preeclamptic women than in normotensive women. The day-night BP difference decreased as average BP rose (diastolic gradient = -0.54 [95% confidence interval (CI) -0.77 to -0.31], systolic gradient = -0.36 [95% CI -0.58 to -0.14], where gradient denotes a unit increase in BP leading to an increase or decrease in the day-night difference). CONCLUSION: The decrease in day-night BP difference observed in preeclampsia is inversely related to average BP. This blunting of the day-night BP difference may be a useful adjunctive measure of disease severity in preeclampsia.

The relative accuracy of sequential same-arm and simultaneous opposite-arm measurements for the intra-arterial validation of blood pressure monitors.

OBJECTIVE: To compare the results of simultaneous opposite-arm and sequential same-arm intra-arterial validation of automated blood pressure monitors. DESIGN: Intra-arterial blood pressure measurements were compared with blood pressure measurements obtained using conventional sphygmomanometry and two automated blood pressure monitors (the Dinamap XL and the SpaceLabs Scout) using a methodology based on the protocol published by the Association for the Advancement of Medical Instrumentation (AAMI) for the intra-arterial validation of automated monitors. METHODS: Thirteen women with radial arterial lines were recruited from the obstetric intensive care unit at Groote Schuur Hospital, Cape Town. For each woman, intra-arterial blood pressure measurements were compared with those obtained by mercury sphygmomanometry and by using the two automated blood pressure monitors with both a sequential same-arm protocol and a simultaneous opposite-arm protocol. The mean and SD of the differences was calculated for each protocol and the results were compared using Student s t test. RESULTS: The differences between the 'means of the differences' for these two protocols never differed by more than 2 mmHg. For individuals the differences between data obtained using the two methodologies were up to 32 mmHg for mercury sphygmomanometry and 18 mmHg for the automated monitors. The differences between the SD of the differences were all less than 3 mmHg except for that of systolic blood pressure obtained by mercury sphygmomanometry, which was 7 mmHg CONCLUSIONS: The results of this study show that a sequential same-arm and a simultaneous opposite-arm comparison of intra-arterial and indirect blood pressure measurements yield similar results.

Management of thromboembolic disease in pregnancy.

Venous thromboembolism (VTE) is the leading cause of maternal mortality and morbidity in developed countries including Singapore. The physiological changes of pregnancy and other factors, such as maternal age, parity, obesity, operative delivery, general anaesthesia and congenital and acquired thrombophilia, further increase the risk of VTE throughout all three trimesters of pregnancy, including the puerperium. VTE has a wide spectrum of clinical presentations and a high index of clinical suspicion is vital. Clinicians should not withhold the use of chest X-rays and ventilation-perfusion (V/Q) lung scans in pregnancy as the radiation emitted is well within the safety limits to the fetus. Most treatment guidelines are based on studies in non-pregnant populations. Heparin is the preferred anticoagulant as it does not cross the placenta and therefore carries no teratogenic risk to the fetus. There is increasing experience and confidence in the use of fixed dose subcutaneous low molecular weight heparin (LMWH) which removes the need for cumbersome monitoring, thereby allowing outpatient treatment. LMWH may also have a lower risk of osteopaenic complications compared to unfractionated heparin. With the exception of acute phase treatment of pulmonary embolism, LMWH is used in all other aspects of the treatment of VTE in pregnancy, including thromboprophylaxis. Risk stratification of women into high and low risk allows judicious use of anticoagulants for thromboprophylaxis. Antenatal thromboprophylaxis with LMWH is reserved for high-risk women, while low-risk women will only require such cover in the postpartum period.

Primary aldosteronism in pregnancy--should it be treated surgically?

We report a case of primary aldosteronism in pregnancy that was treated surgically by removal of the adenoma in the 2nd trimester. Only a few cases have been reported in the English literature due to the rarity of the condition. Primary aldosteronism follows a variable course in pregnancy. In the majority of cases the hypertension and hypokalaemia are made worse, necessitating antihypertensive medication to control the blood pressure. Some of the drugs required for treatment are known to affect the fetus. In a minority of cases the hypertension improves with pregnancy. This is thought to be due to the high levels of progesterone which is an aldosterone antagonist. Primary aldosteronism invariably gets worse in the post partum period, irrespective of the antenatal course of the disease. Surgery seems to be the treatment of choice for this condition, provided the adenoma is localised. It has the advantage of offering an immediate solution, avoids fetal complications of medical treatment and possible deterioration in the post partum period.

Blood pressure in first 10 years of life: the Brompton study.

OBJECTIVES: To determine the normal range of blood pressure and its pattern of change in the first 10 years of life. To estimate at what age (if any) children consistently appear in one part of the blood pressure distribution and at what age familial correlations in blood pressure become significant. DESIGN: Longitudinal cohort study. SETTING: South east England. SUBJECTS: 2088 children of both sexes born consecutively in Farnborough Hospital, Kent, and their parents. MAIN OUTCOME MEASURE: Blood pressure measured by Doppler ultrasonography and sphygmomanometry. RESULTS: Systolic blood pressure rose from a mean of 88.5 mm Hg at age 6 months to 96.2 mm Hg at 8 years measured with a 8 cm cuff and from 89.1 mm Hg at age 5 years to 94.3 mm Hg at age 10 years measured with a 12 cm cuff. The larger cuff gave blood pressure readings about 6 mm Hg lower. This effect was independent of body weight and arm circumference. Diastolic blood pressure rose from 57.8 mm Hg at 5 years to 61.8 mm Hg at 10 years (12 cm cuff). There was only about 1 mm Hg difference between sexes. Blood pressure was correlated with weight, weight adjusted for height, height, and arm circumference at all ages studied. The correlation coefficient of repeated yearly measurements increased steadily with age from 0.28 at 2 years to 0.59 at 10 years. The correlation coefficients between child's blood pressure and mother's average blood pressure increased from 0.1 at age 1 year to 0.23 at age 10. CONCLUSIONS: Blood pressure changes relatively little between the ages of 6 months and 10 years. Yet because of the increasing strength of between occasion and family correlations, children are more consistently occupying a specific part of the blood pressure distribution as they grow older. Studies in children should help determine why some adults have hypertension and others do not.

Initiation of hypertension in utero and its amplification throughout life.

OBJECTIVE: To determine whether the relation between high blood pressure and low birth weight is initiated in utero or during infancy, and whether it changes with age. DESIGN: A longitudinal study of children and three follow up studies of adults. SETTING: Farnborough, Preston, and Hertfordshire, England, and a national sample in Britain. SUBJECTS: 1895 children aged 0-10 years, 3240 men and women aged 36 years, 459 men and women aged 46-54 years, and 1231 men and women aged 59-71 years. The birth weight of all subjects had been recorded. MAIN OUTCOME MEASURE: Systolic blood pressure. RESULTS: At all ages beyond infancy people who had lower birth weight had higher systolic blood pressure. Systolic blood pressure was not related to growth during infancy independently of birth weight. The relation between systolic pressure and birth weight became larger with increasing age so that, after current body mass was allowed for, systolic pressure at ages 64-71 years decreased by 5.2 mm Hg (95% confidence interval 1.8 to 8.6) for every kg increase in birth weight. CONCLUSIONS: Essential hypertension is initiated in fetal life. A raised blood pressure is then amplified from infancy to old age, perhaps by a positive feedback mechanism.