Identifying hypertension in pregnancy using electronic medical records: The importance of blood pressure values.

OBJECTIVE: To incorporate blood pressure (BP), diagnoses codes, and medication fills from electronic medical records (EMR) to identify pregnant women with hypertension. STUDY DESIGN: A retrospective cohort study of singleton pregnancies at three US integrated health delivery systems during 2005-2014. MAIN OUTCOME MEASURES: Women were considered hypertensive if they had any of the following: (1) ≥2 high BPs (≥140/90 mmHg) within 30 days during pregnancy (High BP); (2) an antihypertensive medication fill in the 120 days before pregnancy and a hypertension diagnosis from 1 year prior to pregnancy through 20 weeks gestation (Treated Chronic Hypertension); or (3) a high BP, a hypertension diagnosis, and a prescription fill within 7 days during pregnancy (Rapid Treatment). We described characteristics of these pregnancies and conducted medical record review to understand hypertension presence and severity. RESULTS: Of 566,624 pregnancies, 27,049 (4.8%) met our hypertension case definition: 24,140 (89.2%) with High BP, 5,409 (20.0%) with Treated Chronic Hypertension, and 5,363 (19.8%) with Rapid Treatment (not mutually exclusive). Of hypertensive pregnancies, 19,298 (71.3%) received a diagnosis, 9,762 (36.1%) received treatment and 11,226 (41.5%) had a BP ≥ 160/110. In a random sample (n = 55) of the 7,559 pregnancies meeting the High BP criterion with no hypertension diagnosis, clinical statements about hypertension were found in medical records for 58% of them. CONCLUSION: Incorporating EMR BP identified many pregnant women with hypertension who would have been missed by using diagnosis codes alone. Future studies should seek to incorporate BP to study treatment and outcomes of hypertension in pregnancy.

Prevalence and predictors of right ventricular diastolic dysfunction in peripartum cardiomyopathy.

BACKGROUND: This study aimed to assess the prevalence of right ventricular diastolic dysfunction (RVDD) and its potential predictors in peripartum cardiomyopathy (PPCM) patients. METHODS: This was a cross-sectional study carried out in Nigeria. RVDD was defined and graded using Doppler filling and myocardial tissue Doppler velocities obtained at tricuspid annular level. RESULTS: Forty-three subjects with PPCM and mean age of 26.6 ± 7.0 years were recruited over 6 months. RVDD was found in 30 (69.8 %) subjects, of whom 16 (53.3 %) had grade I, 12 (40.0 %) had grade II and 2 (6.7 %) had grade III severity. RV systolic dysfunction (RVSD), defined as RV fractional area change <35 %, was found in 88.4 %, while combined RVSD and RVDD was found in 58.1 % of patients. Subjects with RVDD had significantly higher tricuspid E/e' ratio (5.1 ± 2.8 versus 3.5 ± 1.0, p = 0.012) and prevalence of pulmonary hypertension (76.7 versus 46.2 %; p < 0.05), and lower serum selenium concentration (55.6 ± 12.1 versus 72.5 ± 12.0 µg/L, p = 0.001) than those with preserved RV diastolic function. Regression analyses showed serum selenium [odds ratio (OR) = 1.14; 95 % confidence interval (CI) = 1.0-1.3; p = 0.049] and combined RVSD and pulmonary hypertension (OR = 79.2; CI = 3.9-1593.7; p = 0.004) as the only predictors of RVDD, and serum selenium <70 µg/L increased the odds of RVDD by 6.67-fold (CI = 1.18-37.78; p = 0.032). CONCLUSIONS: Both RVDD and RVSD were common in PPCM patients. Selenium deficiency and combined RVSD and pulmonary hypertension seemed to be the only determinants of RVDD in this small cohort, a finding that needs verification in a larger sample of patients.

Women's values and preferences for thromboprophylaxis during pregnancy: a comparison of direct-choice and decision analysis using patient specific utilities.

BACKGROUND: Women with a history of venous thromboembolism (VTE) have an increased recurrence risk during pregnancy. Low molecular weight heparin (LMWH) reduces this risk, but is costly, burdensome, and may increase risk of bleeding. The decision to start thromboprophylaxis during pregnancy is sensitive to women's values and preferences. Our objective was to compare women's choices using a holistic approach in which they were presented all of the relevant information (direct-choice) versus a personalized decision analysis in which a mathematical model incorporated their preferences and VTE risk to make a treatment recommendation. METHODS: Multicenter, international study. Structured interviews were on women with a history of VTE who were pregnant, planning, or considering pregnancy. Women indicated their willingness to receive thromboprophylaxis based on scenarios using personalized estimates of VTE recurrence and bleeding risks. We also obtained women's values for health outcomes using a visual analog scale. We performed individualized decision analyses for each participant and compared model recommendations to decisions made when presented with the direct-choice exercise. RESULTS: Of the 123 women in the study, the decision model recommended LMWH for 51 women and recommended against LMWH for 72 women. 12% (6/51) of women for whom the decision model recommended thromboprophylaxis chose not to take LMWH; 72% (52/72) of women for whom the decision model recommended against thromboprophylaxis chose LMWH. CONCLUSIONS: We observed a high degree of discordance between decisions in the direct-choice exercise and decision model recommendations. Although which approach best captures individuals' true values remains uncertain, personalized decision support tools presenting results based on personalized risks and values may improve decision making.

Uso de hierro en forma de medicamento en gestantes colombianas / Pregnant Colombian females' iron in take in drug form

Objetivo Caracterizar el consumo de hierro en forma de medicamento en un grupo de embarazadas colombianas. Metodología Estudio observacional descriptivo, se obtuvo información de mujeres en control prenatal y/o atención del parto en 4 ciudades de Colombia. Las fuentes de información fueron entrevistas a gestantes y registros de historia clínica. Resultados La muestra fue de 1 637 mujeres en 15 instituciones. A 1 396 mujeres (85,3 %) les recomendaron consumir hierro, recomendación realizada por médico al 85,3 % de ellas, el 86,8 % tuvo adherencia al tratamiento. Al 84,7 % el hierro fue suministrado por la empresa aseguradora de salud, el 11,9 % lo compró a sus expensas. El 90,0 % de gestantes anémicas y el 82,8 % de las no anémicas consumieron hierro en forma de medicamento, en conjunto, en el 37,2 % de las gestantes el consumo de suplencia de hierro fue pertinente (es decir, lo necesitaban, se les recomendó y lo consumieron o no le necesitaban, no se recomendó y/o no lo consumieron). Discusión Se recomienda y se consume hierro independientemente de presentar anemia. Se invita a reflexionar sobre la utilidad de los programas que promueven el consumo masivo de esta sustancia en forma de medicamento durante el embarazo, programas que parecen desconocer las causas fundamentales de los problemas nutricionales que aquejan a la población.

Objective Describing a group of pregnant Colombian females' iron intake, in drug form. Methodology This was an observational descriptive study; information was collected in 4 Colombian cities regarding pregnant females during antenatal control or when giving birth. Information sources consisted of interviews with pregnant women and their clinical records. Results The sample consisted of 1,637 female sat tending 15 institutions. An iron intake was recommended for1, 396 women (85.3 %); a doctor made such recommendation in 85.3 % of cases and adherence was 86.8 %. Health insurance was used by 84.7 % of the females for supplying iron; 11.9 % of them bought it themselves. Iron intake as medication for anemic pregnant females was 90.0 % and 82.8 % in non-anemic ones. Iron intake supply was appropriate in 37.2 % of the pregnant females (i.e. they needed it, someone recommended it for them and they consumed it, or they didn't need it, someone didn't recommend it to them and/or they did not take it). Discussion Iron intake was recommended and consumed regardless of anemia status. The results invite to think on the usefulness of programs promoting the mass intake of iron as a medication during pregnancy. Such programs seem to be unaware of the fundamental causes of people's nutritional problems.

[Pregnant Colombian females' iron intake in drug form]. / Uso de hierro en forma de medicamento en gestantes colombianas.

OBJECTIVE: Describing a group of pregnant Colombian females' iron intake, in drug form. METHODOLOGY: This was an observational descriptive study; information was collected in 4 Colombian cities regarding pregnant females during antenatal control or when giving birth. Information sources consisted of interviews with pregnant women and their clinical records. RESULTS: The sample consisted of 1,637 females attending 15 institutions. An iron intake was recommended for 1, 396 women (85.3 %); a doctor made such recommendation in 85.3 % of cases and adherence was 86.8 %. Health insurance was used by 84.7 % of the females for supplying iron; 11.9 % of them bought it themselves. Iron intake as medication for anemic pregnant females was 90.0 % and 82.8 % in non-anemic ones. Iron intake supply was appropriate in 37.2 % of the pregnant females (i.e. they needed it, someone recommended it for them and they consumed it, or they didn't need it, someone didn't recommend it to them and/or they did not take it). DISCUSSION: Iron intake was recommended and consumed regardless of anemia status. The results invite to think on the usefulness of programs promoting the mass intake of iron as a medication during pregnancy. Such programs seem to be unaware of the fundamental causes of people's nutritional problems.

Reducing stillbirths: prevention and management of medical disorders and infections during pregnancy.

BACKGROUND: An estimated two-thirds of the world's 3.2 million stillbirths occur antenatally, prior to labour, and are often overlooked in policy and programs. Poorly recognised, untreated or inadequately treated maternal infections such as syphilis and malaria, and maternal conditions including hypertensive disorders, are known risk factors for stillbirth. METHODS: We undertook a systematic review of the evidence for 16 antenatal interventions with the potential to prevent stillbirths. We searched a range of sources including PubMed and the Cochrane Library. For interventions with prior Cochrane reviews, we conducted additional meta-analyses including eligible newer randomised controlled trials following the Cochrane protocol. We focused on interventions deliverable at the community level in low-/middle-income countries, where the burden of stillbirths is greatest. RESULTS: Few of the studies we included reported stillbirth as an outcome; most that did were underpowered to assess this outcome. While Cochrane reviews or meta-analyses were available for many interventions, few focused on stillbirth or perinatal mortality as outcomes, and evidence was frequently conflicting. Several interventions showed clear evidence of impact on stillbirths, including heparin therapy for certain maternal indications; syphilis screening and treatment; and insecticide-treated bed nets for prevention of malaria. Other interventions, such as management of obstetric intrahepatic cholestasis, maternal anti-helminthic treatment, and intermittent preventive treatment of malaria, showed promising impact on stillbirth rates but require confirmatory studies. Several interventions reduced known risk factors for stillbirth (e.g., anti-hypertensive drugs for chronic hypertension), yet failed to show statistically significant impact on stillbirth or perinatal mortality rates. Periodontal disease emerged as a clear risk factor for stillbirth but no interventions have reduced stillbirth rates. CONCLUSION: Evidence for some newly recognised risk factors for stillbirth, including periodontal disease, suggests the need for large, appropriately designed randomised trials to test whether intervention can minimise these risks and prevent stillbirths. Existing evidence strongly supports infection control measures, including syphilis screening and treatment and malaria prophylaxis in endemic areas, for preventing antepartum stillbirths. These interventions should be incorporated into antenatal care programs based on attributable risks and burden of disease.

More reasons why men and women are not the same (gender differences in electrophysiology and arrhythmias).

It has become increasingly apparent in recent years that there are important differences in the presentation and clinical course of many cardiovascular disorders in men and women. These gender differences extend to clinical cardiac electrophysiology, with respect to basic electrophysiology as well as the presentation and clinical courses of many arrhythmias. Women have been noted to have higher heart rates at rest and longer corrected QT intervals compared with men. Differences in gender hormones may explain some of these findings, but precisely how is still not well understood. Differences have also been documented in the incidence and prevalence of specific arrhythmias, including atrial fibrillation, other supraventricular tachycardias, and sudden cardiac death. Variations in arrhythmia frequency with respect to the menstrual cycle have been observed. In addition, an increase in arrhythmia frequency or the new onset of arrhythmias has been noted during pregnancy. With the increasing use of implantable cardioverter defibrillators and cardiac resynchronization therapy, it has been shown that men and women derive equal survival and symptom reduction benefit. However, it has been found that the use of these devices in women is much lower than would be expected from the prevalence of disease in the population. The reasons for this lower utilization rate are not well understood and remain to be explored. In conclusion, the goal of this review is to summarize the currently available published reports regarding gender differences in cardiac electrophysiology and arrhythmias and to provide an update from recent studies.

Abortion, changed paternity, and risk of preeclampsia in nulliparous women.

A prior birth confers a strong protective effect against preeclampsia, whereas a prior abortion confers a weaker protective effect. Parous women who change partners in a subsequent pregnancy appear to lose the protective effect of a prior birth. This study (Calcium for Preeclampsia Prevention Trial, 1992-1995) examines whether nulliparous women with a prior abortion who change partners also lose the protective effect of the prior pregnancy. A cohort analysis was conducted among participants in this large clinical trial of calcium supplementation to prevent preeclampsia. Subjects were nulliparous, had one prior pregnancy or less, delivered after 20 weeks' gestation, and were interviewed at 5-21 weeks about prior pregnancies and paternity. Women without a history of abortion served as the reference group in logistic regression analyses. Women with a history of abortion who conceived again with the same partner had nearly half the risk of preeclampsia (adjusted odds ratio = 0.54, 95 percent confidence interval: 0.31, 0.97). In contrast, women with an abortion history who conceived with a new partner had the same risk of preeclampsia as women without a history of abortion (adjusted odds ratio = 1.03, 95 percent confidence interval: 0.72, 1.47). Thus, the protective effect of a prior abortion operated only among women who conceived again with the same partner. An immune-based etiologic mechanism is proposed, whereby prolonged exposure to fetal antigens from a previous pregnancy protects against preeclampsia in a subsequent pregnancy with the same father.

Risk of gestational hypertension in relation to folic acid supplementation during pregnancy.

The authors investigated the association between folic acid supplementation and gestational hypertension. The study population included women with nonmalformed infants in the United States and Canada who were participating in the Slone Epidemiology Center Birth Defects Study between 1993 and 2000. Women were interviewed within 6 months after delivery about sociodemographic and medical factors, the occurrence of hypertension with or without preeclampsia, and multivitamin use in pregnancy. Relative risks, adjusted for weight, parity, twin pregnancy, diabetes, smoking, education, and family income, were estimated using Cox regression models. Of 2,100 women, 204 (9.7%) reported gestational hypertension (onset after the 20th week of gestation). The multivariate-adjusted relative risk of developing gestational hypertension during the month after folic acid supplementation, compared with not using folic acid during that same month, was 0.55 (95% confidence interval: 0.39, 0.79). This finding suggests that folic acid-containing multivitamins may reduce the risk of gestational hypertension.

Factor analysis, including antihypertensive medication, of the outcome of pregnancy in pregnancy-associated hypertension.

AIM: To study the influence of different maternal factors, including antihypertensive medication, on the outcome of pregnancy in primi- and multiparas with pregnancy-associated hypertension. METHODS: A retrospective, multiple-variate analysis was undertaken of the influence of several maternal factors, including antihypertensive medication, on fetal death and Apgar scores and the correlation between the medication and the number of caesarean sections in 127 episodes of pregnancy-associated hypertension was studied for the whole group as well as for primi- and multiparas separately. Of the multiparas, 40.8% had a history of preeclampsia, 19.7% of chronic hypertension and 9.2% of diabetes mellitus. Antihypertensive treatment aimed at achieving a blood pressure of 140/90 mm Hg. Forty-one patients (32.3%) received intravenous hydralazine, 25 (19.7%) received nifedipine per os and 44 (34.6%) received labetalol per os. RESULTS: The maximum systolic and diastolic blood pressure in the patients given intravenous hydralazine, nifedipine per os or labetalol per os did not differ, whereas in the multiparas, the number of patients who reached the target blood pressure while using labetalol was higher than with the two other medications, especially in comparison with intravenous hydralazine. For the primiparas, the time of delivery was the only factor with a significant impact on the Apgar scores. In the multiparas, there was an additional negative influence of the use of intravenous hydralazine. This was not seen in the patients using nifedipine and labetalol. CONCLUSIONS: The results suggest that in multiparas, intravenous hydralazine is possibly associated with more fetal distress when compared to primiparas.

Calcium and low-dose aspirin prophylaxis in women at high risk of pregnancy-induced hypertension.

OBJECTIVE: The objectives of the study were to confirm the validity of using oscillometric measurement of MAP in the left lateral position to identify those at high risk for developing pregnancy-induced hypertension (PIH), and to assess and compare the efficacy of prophylaxis with low-dose aspirin or calcium supplementation in high-risk patients. STUDY DESIGN: A prospective study in pregnancy; 500 normotensive, primigravid Chinese women were recruited in the second trimester of pregnancy on the basis of 80 mm Hg > or = MAP < 106 mm Hg in the antenatal clinic. They were then screened by Dinamap in a research setting, measuring MAP in the left lateral position after rest and using a cutoff value of 60 mm Hg for inclusion in the randomized study. Randomization was divided into three groups: control, low-dose aspirin, and calcium supplementation. After delivery, patients were classified as either having remained normotensive or having developed PIH, with or without proteinuria. RESULTS: The incidence of both proteinuric and nonproteinuric PIH was significantly lower in patients screened out as low risk than in those selected as high risk using a critical value of 60 mm Hg for left lateral MAP (p < 0.05). The incidence of proteinuric PIH was significantly lower in patients given low-dose aspirin than in the control group (p < 0.05). However, the confidence intervals for the effect were wide, comparable with aspirin having no effect or leading to a 16-fold reduction in the risk of preeclampsia. For those given calcium supplementation, the reduction was not significant. There was no significant difference in the incidence of nonproteinuric PIH between the control group and the two groups receiving prophylaxis. CONCLUSION: Oscillometric measurement of second-trimester left lateral MAP is a valid predictor of proteinuric PIH. Low-dose aspirin may offer a degree of protection from proteinuric PIH in these high-risk women. Calcium supplementation was not shown to significantly reduce the incidence of PIH.

Influence of calcium intake on gestational hypertension.

Calcium intake during the third trimester of pregnancy was determined in 82 pregnant women by recording the consumption of foods over a 5-day period and by calculation of the quantity of this element provided by dietary supplements. For each subject, blood pressures were measured once per week using an aneroid sphygmomanometer, to detect and analyze differences in calcium intake between those with normal blood pressure and those suffering from gestational hypertension (7.3%). Calcium intake was significantly lower amongst subjects with high blood pressure (757.7 +/- 154.5 compared to 986.4 +/- 502.3 mg/day in normotensive subjects). The relationship between calcium intake and blood pressure was independent of other variables such as body mass index, number of previous pregnancies, weight gain, subject age or hematocrit levels. Though further investigation is needed, the results obtained seem to support the idea that pregnant women should try to maintain an optimal calcium intake.

Hypertension in pregnancy: a study of the Asia-Oceania region.

A review of the management practices and problems surrounding hypertension in pregnancy in the Asia-Oceania region was made. This review was achieved by surveying institutions in the region. Sixteen countries responded to this survey and the results were analysed. Both rural and city hospitals were involved in the survey. The centres were selected by members of the Maternal Perinatal Committee of the Asia-Oceania Federation of Obstetrics and Gynaecology (AOFOG) under whose patronage the survey was performed. Analysis of the survey revealed a number of problems which could be addressed by appropriate educational interventions, these included drug therapies and protocols, deficiencies in governmental support especially in transport and centralised intensive care facilities. Public awareness was also a priority to be addressed. The role of the traditional birth attendant has been increasingly recognised as a resource which could be utilised. This is highlighted in this survey where there are countries who will be dependent on these carers for the next 10 years at least. Their place in the management of hypertension is discussed.

Trial of calcium to prevent preeclampsia.

BACKGROUND: Previous trials have suggested that calcium supplementation during pregnancy may reduce the risk of preeclampsia. However, differences in study design and a low dietary calcium intake in the populations studied limit acceptance of the data. METHODS: We randomly assigned 4589 healthy nulliparous women who were 13 to 21 weeks pregnant to receive daily treatment with either 2 g of elemental calcium or placebo for the remainder of their pregnancies. Surveillance for preeclampsia was conducted by personnel unaware of treatment-group assignments, using standardized measurements of blood pressure and urinary protein excretion at uniformly scheduled prenatal visits, protocols for monitoring these measurements during the hospitalization for delivery, and reviews of medical records of unscheduled outpatient visits and all hospitalizations. RESULTS: Calcium supplementation did not significantly reduce the incidence or severity of preeclampsia or delay its onset. Preeclampsia occurred in 158 of the 2295 women in the calcium group (6.9 percent) and 168 of the 2294 women in the placebo group (7.3 percent) (relative risk, 0.94; 95 percent confidence interval, 0.76 to 1.16). There were no significant differences between the two groups in the prevalence of pregnancy-associated hypertension without preeclampsia (15.3 percent vs. 17.3 percent) or of all hypertensive disorders (22.2 percent vs. 24.6 percent). The mean systolic and diastolic blood pressures during pregnancy were similar in both groups. Calcium did not reduce the numbers of preterm deliveries, small-for-gestational-age births, or fetal and neonatal deaths; nor did it increase urolithiasis during pregnancy. CONCLUSIONS: Calcium supplementation during pregnancy did not prevent preeclampsia, pregnancy-associated hypertension, or adverse perinatal outcomes in healthy nulliparous women.

Effect of calcium supplementation on pregnancy-induced hypertension and preeclampsia: a meta-analysis of randomized controlled trials.

OBJECTIVE: To review the effect of calcium supplementation during pregnancy on blood pressure, preeclampsia, and adverse outcomes of pregnancy. DATA SOURCE: We searched MEDLINE and EMBASE for 1966 to May 1994. We contacted authors of eligible trials to ensure accuracy and completeness of data and to identify unpublished trials. STUDY SELECTION: Fourteen randomized trials involving 2459 women were eligible. DATA EXTRACTION: Reviewers working independently in pairs abstracted data and assessed validity according to six quality criteria. DATA SYNTHESIS: Each trial yielded differences in blood pressure change between calcium supplementation and control groups that we weighted by the inverse of the variance. The pooled analysis showed a reduction in systolic blood pressure of -5.40 mm Hg (95% confidence interval [CI], -7.81 to -3.00 mm Hg; P<.001) and in diastolic blood pressure of -3.44 mm Hg (95% CI, -5.20 to -1.68 mm Hg; P<.001). The odds ratio for preeclampsia in women with calcium supplementation compared with placebo was 0.38 (95% CI, 0.22 to 0.65). CONCLUSIONS: Calcium supplementation during pregnancy leads to an important reduction in systolic and diastolic blood pressure and preeclampsia. While pregnant women at risk of preeclampsia should consider taking calcium, many more patient events are needed to confirm calcium's impact on maternal and fetal morbidity.

Calcium supplementation prevents pregnancy-induced hypertension by increasing the production of vascular nitric oxide.

Pregnancy-induced hypertension (PIH) remains a common cause of maternal and fetal morbidity and mortality. During the past 7 years, some progress has been made in the prevention of PIH. Specifically, clinical studies have shown that supplementation with calcium can significantly reduce the frequency of PIH, specially in populations with a low calcium intake. We have suggested that, in such a population, calcium supplementation is a safe and effective measure for reducing the frequency of PIH. Thus, the purpose of this article is to advance a hypothesis about the mechanism by which calcium supplementation reduces the risk of PIH. We propose that dietary calcium supplementation reduces the frequency of PIH by maintaining the serum ionized calcium level which is crucial for the production of endothelial nitric oxide, the increased generation of which maintains the vasodilatation that is characteristic of normal pregnancy.

Prevention of pregnancy-induced hypertension by calcium supplementation in angiotensin II-sensitive patients.

OBJECTIVE: To evaluate the efficacy of oral supplemental calcium in reducing the incidence of pregnancy-induced hypertension (gestational hypertension or preeclampsia) in angiotensin-sensitive nulliparas. METHODS: Sensitivity to intravenously infused angiotensin was determined at 24-28 weeks' gestation in 281 nulliparous women who had positive roll-over tests. Angiotensin-sensitive women were given 2 g/day of oral elemental calcium or placebo in a randomized, double-blind clinical trial. The tablets were dispensed by the hospital pharmacy in serially numbered computerized pill bottles so as to assess compliance. Repeat angiotensin sensitivity test was performed at 34-36 weeks' gestation. RESULTS: Sixty-three of 67 angiotensin-sensitive nulliparas were evaluable; 29 received calcium and 34 received placebo tablets. Four of 29 calcium-treated subjects (13.8%, 95% confidence interval [CI] 4-32%) developed preeclampsia, compared to 15 of 34 (44.1%, 95% CI 27-62%) in the placebo group (relative risk [RR] 0.37, 95% CI 0.15-0.92; P = .01). The incidence of any type of hypertension was nine of 29 (31%, 95% CI 15-51%) with calcium treatment, compared to 22 of 34 (64.7%, 95% CI 46-80%) with placebo (RR 0.46, 95% CI 0.25-0.86; P = .01). CONCLUSION: Calcium supplementation given in pregnancy to high-risk nulliparas reduces the incidence of pregnancy-induced hypertension.