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Background Antenatal corticosteroids (ACS) have long been regarded as a cornerstone intervention in mitigating the adverse effects of a preterm birth. However, the safety and efficacy of ACS in hospitals in low-resource countries has not been established in an efficacy trial despite their widespread use. Findings of a large cluster-randomized trial in six low- and middle-income countries showed that efforts to scale up ACS use in low-resource settings can lead to harm. There is equipoise regarding the benefits and harms of ACS use in hospitals in low-resource countries. This randomized controlled trial aims to determine whether ACS are safe and efficacious when given to women at risk of imminent birth in the early preterm period, in hospitals in low-resource countries. Methods/design The trial design is a parallel, two-arm, double-blind, individually randomized, placebo-controlled trial of ACS (dexamethasone) for women at risk of imminent preterm birth. The trial will recruit 6018 women in participating hospitals across five low-resource countries (Bangladesh, India, Kenya, Nigeria and Pakistan). The primary objectives are to compare the efficacy of dexamethasone with placebo on survival of the baby and maternal infectious morbidity. The primary outcomes are: 1) neonatal death (to 28 completed days of life); 2) any baby death (any stillbirth postrandomization or neonatal death); and 3) a composite outcome to assess possible maternal bacterial infections. The trial will recruit eligible, consenting pregnant women from 26 weeks 0 days to 33 weeks 6 days gestation with confirmed live fetuses, in whom birth is planned or expected within 48 h. The intervention comprises a regimen of intramuscular dexamethasone sodium phosphate. The comparison is an identical placebo regimen (normal saline). A total of 6018 women will be recruited to detect a reduction of 15% or more in neonatal deaths in a two-sided 5% significance test with 90% power (including 10% loss to follow-up). Discussion Findings of this trial will guide clinicians, programme managers and policymakers on the safety and efficacy of ACS in hospitals in low-resource countries. The trial findings will inform updating of the World Health Organization’s global recommendations on ACS use. Trial registration ACTRN12617000476336. Registered on 31 March 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3488-z) contains supplementary material, which is available to authorized users.

IntroductionAbortion-related complications are a significant cause of morbidity and mortality among women in many Latin American and Caribbean (LAC) countries. The objective of this study was to characterise abortion-related complication severity, describe the management of these complications and report women’s experiences with abortion care in selected countries of the Americas region.MethodsThis is a cross-sectional study of 70 health facilities across six countries in the region. We collected data on women’s characteristics including socio-demographics, obstetric history, clinical information, management procedures and using Audio Computer-Assisted Self-Interviewing (ACASI) survey the experience of abortion care. Descriptive bivariate analysis was performed for women’s characteristics, management of complications and reported experiences of abortion care by severity of complications, organised in five hierarchical mutually exclusive categories based on indicators present at assessment. Generalised linear estimation models were used to assess the association between women’s characteristics and severity of complications.ResultsWe collected data on 7983 women with abortion-related complications. Complications were classified as mild (46.3%), moderate (49.5%), potentially life-threatening (3.1%), near-miss cases (1.1%) and deaths (0.2%). Being single, having a gestational age of ≥13 weeks and having expelled products of conception before arrival at the facility were significantly associated with experiencing severe maternal outcomes compared with mild complications.Management of abortion-related complications included both uterotonics and uterine evacuation for two-thirds of the women while one-third received uterine evacuation only. Surgical uterine evacuation was performed in 93.2% (7437/7983) of women, being vacuum aspiration the most common one (5007/7437, 67.4%).Of the 327 women who completed the ACASI survey, 16.5% reported having an induced abortion, 12.5% of the women stated that they were not given explanations regarding their care nor were able to ask questions during their examination and treatment with percentages increasing with the severity of morbidity.ConclusionsThis is one of the first studies using a standardised methodology to measure severity of abortion-related complications and women’s experiences with abortion care in LAC. Results aim to inform policies and programmes addressing sexual and reproductive rights and health in the region.

Calcium supplementation in mothers with low calcium intake has been of interest recently because of its association with optimal fetal growth and improved pre-eclampsia-related outcomes. While the effects of calcium supplementation have demonstrated benefits in prolonging gestation and subsequently improving birthweight, no specific studies have identified the longitudinal effects of supplementation on fetal growth in utero. Data were analysed in the context of the World Health Organization trial of calcium supplementation in calcium-deficient women. Five hundred and ten healthy, primiparous pregnant Argentinean women were randomised (at

Cluster-based studies involving aggregate units such as hospitals or medical practices are increasingly being used in healthcare evaluation. An important characteristic of such studies is the presence of intracluster correlation, typically quantified by the intracluster correlation coefficient (ICC). Sample size calculations for cluster-based studies need to account for the ICC, or risk underestimating the sample size required to yield the desired levels of power and significance. In this article, we present values for ICCs that were obtained from data on 97,095 pregnancies and 98,072 births taking place in a representative sample of 120 hospitals in eight Latin American countries. We present ICCs for 86 variables measured on mothers and newborns from pregnancy to the time of hospital discharge, including 'process variables' representing actual medical care received for each mother and newborn. Process variables are of primary interest in the field of implementation research. We found that overall, ICCs ranged from a minimum of 0.0003 to a maximum of 0.563 (median 0.067). For maternal and newborn outcome variables, the median ICCs were 0.011 (interquartile range 0.007-0.037) and 0.054 (interquartile range 0.013-0.075) respectively; however, for process variables, the median was 0.161 (interquartile range 0.072-0.328). Thus, we confirm previous findings that process variables tend to have higher ICCs than outcome variables. We demonstrate that ICCs generally tend to increase with higher prevalences (close to 0.5). These results can help researchers calculate the required sample size for future research studies in maternal and perinatal health.

NICHD NIH HHS World Health Organization ObjectiveTo generate a global reference for caesarean section (CS) rates at health facilities. DesignCross-sectional study. SettingHealth facilities from 43 countries. Population/SampleThirty eight thousand three hundred and twenty-four women giving birth from 22 countries for model building and 10045875 women giving birth from 43 countries for model testing. MethodsWe hypothesised that mathematical models could determine the relationship between clinical-obstetric characteristics and CS. These models generated probabilities of CS that could be compared with the observed CS rates. We devised a three-step approach to generate the global benchmark of CS rates at health facilities: creation of a multi-country reference population, building mathematical models, and testing these models. Main outcome measuresArea under the ROC curves, diagnostic odds ratio, expected CS rate, observed CS rate. ResultsAccording to the different versions of the model, areas under the ROC curves suggested a good discriminatory capacity of C-Model, with summary estimates ranging from 0.832 to 0.844. The C-Model was able to generate expected CS rates adjusted for the case-mix of the obstetric population. We have also prepared an e-calculator to facilitate use of C-Model (). ConclusionsThis article describes the development of a global reference for CS rates. Based on maternal characteristics, this tool was able to generate an individualised expected CS rate for health facilities or groups of health facilities. With C-Model, obstetric teams, health system managers, health facilities, health insurance companies, and governments can produce a customised reference CS rate for assessing use (and overuse) of CS. Tweetable abstractThe C-Model provides a customized benchmark for caesarean section rates in health facilities and systems. Tweetable abstract The C-Model provides a customized benchmark for caesarean section rates in health facilities and systems. Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Social Med, Av Bandeirantes, BR-3900 Ribeirao Preto, Brazil WHO, World Bank Special Programme Res Dev & Res Traini, UNDP UNFPA UNICEF WHO, Dept Reprod Hlth & Res, CH-1211 Geneva, Switzerland Univ Paris 05, Sorbonne Paris Cite, UMR 216, Inst Dev Res, Paris, France WHO Reg Off Amer, Women & Reprod Hlth CLAP WR, Latin Amer Ctr Perinatol, Montevideo, Uruguay Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA Paris Descartes Univ, Ctr Epidemiol & Biostat, Obstetr Perinatal & Pediat Epidemiol Res Team, Inserm U1153, Paris, France Natl Inst Publ Hlth, Ctr Populat Hlth Res, Cuernavaca, Morelos, Mexico Univ Technol, Fac Hlth, Sydney, NSW, Australia Natl Ctr Child Hlth & Dev, Dept Hlth Policy, Tokyo, Japan Ctr Rosarino Estudios Perinat, Rosario, Argentina Lindsay Stewart R&D Ctr, Off Res & Clin Audit, Royal Coll Obstetricians & Gynaecologists, London, England London Sch Hyg & Trop Med, Dept Hlth Serv Res & Policy, London WC1, England Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Shanghai Key Lab Childrens Environ Hlth,Minist Ed, Shanghai 200030, Peoples R China Univ Estadual Campinas, Sch Med Sci, Dept Obstet & Gynaecol, Campinas, SP, Brazil Family Hlth Bur, Minist Hlth, Colombo, Sri Lanka Fiocruz MS, ENSP, BR-21045900 Rio De Janeiro, Brazil Natl Inst Hlth & Welf, Helsinki, Finland Univ Tokyo, Grad Sch Med, Dept Paediat, Tokyo, Japan Bayer Krankenhausgesellschaft, Bayer Arbeitsgemeinschaft Qualitatssicherun Stati, Munich, Germany Khon Kaen Univ, Fac Med, Dept Obstet & Gynecol, Khon, Kaen, Thailand Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Obstet & Gynaecol, BR-14049 Ribeirao Preto, Brazil Minist Sante, Direct Sante Famille, Ouagadougou, Burkina Faso Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA Univ Mongolia, Hlth Sci, Sch Publ Hlth, Ulaanbaatar, Mongol Peo Rep GLIDE Tech Cooperat & Res, Ribeirao Preto, SP, Brazil Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Paediat, BR-14049 Ribeirao Preto, SP, Brazil Univ Calif San Francisco, Dept Obstet & Gynaecol & Global Hlth Sci, San Francisco, CA 94143 USA Khon Kaen Univ, Fac Publ Hlth, Dept Biostat & Demog, Khon Kaen, Thailand Univ Fed Sao Paulo, Sch Med Sao Paulo, Dept Obstet, Sao Paulo, Brazil Inter Amer Dev Bank, Social Protect & Hlth Div, Mexico City, DF, Mexico Fortis Mem Res Inst, Gurgaon, Haryana, India Hosp Nacl Itaugua, Itaugua, Paraguay Univ Fed Sao Paulo, Sch Med Sao Paulo, Dept Obstet, Sao Paulo, Brazil NICHD NIH HHS: T32 HD052460 World Health Organization: 001 Web of Science

OBJECTIVE: To report stillbirth and early neonatal mortality and to quantify the relative importance of different primary obstetric causes of perinatal mortality in 171 perinatal deaths from 7993 pregnancies that ended after 28 weeks in nulliparous women. METHODS: A review of all stillbirths and early newborn deaths reported in the WHO calcium supplementation trial for the prevention of pre-eclampsia conducted at seven WHO collaborating centres in Argentina, Egypt, India, Peru, South Africa and Viet Nam. We used the Baird-Pattinson system to assign primary obstetric causes of death and classified causes of early neonatal death using the International classification of diseases and related health problems, Tenth revision (ICD-10). FINDINGS: Stillbirth rate was 12.5 per 1000 births and early neonatal mortality rate was 9.0 per 1000 live births. Spontaneous preterm delivery and hypertensive disorders were the most common obstetric events leading to perinatal deaths (28.7% and 23.6%, respectively). Prematurity was the main cause of early neonatal deaths (62%). CONCLUSIONS: Advancements in the care of premature infants and prevention of spontaneous preterm labour and hypertensive disorders of pregnancy could lead to a substantial decrease in perinatal mortality in hospital settings in developing countries.

Objective Preeclampsia, gestational hypertension, and unexplained intrauterine growth restriction may have similar determinants and consequences. In this study, we compared determinants and perinatal outcomes associated with these obstetric conditions. Study design We analyzed 39,615 pregnancies (data from the WHO Antenatal Care Trial), of which 2.2% were complicated by preeclampsia, 7.0% by gestational hypertension, and 8.1% by unexplained intrauterine growth restriction (ie, not associated with maternal smoking, maternal undernutrition, preeclampsia, gestational hypertension, or congenital malformations). We compared the risk factors associated with these groups. Fetal death, preterm delivery, and severe neonatal morbidity and mortality were the primary outcomes. Logistic regression analyses were adjusted for study site, socioeconomic status, and (if appropriate) birth weight and gestational age. Results Diabetes, renal or cardiac disease, previous preeclampsia, urinary tract infection, high maternal age, twin pregnancy, and obesity increased the risk of both hypertensive conditions. Previous large-for-age birth, reproductive tract surgery, antepartum hemorrhage and reproductive tract infection increased the risk for gestational hypertension only. Independent of maternal age, primiparity was a risk factor only for preeclampsia. Both preeclampsia and gestational hypertension were associated with increased risk for fetal death and severe neonatal morbidity and mortality. Mothers with preeclampsia compared with those with unexplained intrauterine growth restriction were more likely to have a history of diabetes, renal or cardiac disease, chronic hypertension, previous preeclampsia, body mass index more than 30 kg/cm 2 , urinary tract infection and extremes of maternal age. Conversely, unexplained intrauterine growth restriction was associated with higher risk of low birth weight in previous pregnancies, but not with previous preeclampsia. Both conditions increased the risk for perinatal outcomes independently but preeclampsia was associated with considerable higher risk. Conclusion Preeclampsia and gestational hypertension shared many risk factors, although there are differences that need further evaluation. Both conditions significantly increased morbidity and mortality. Conversely, preeclampsia and unexplained intrauterine growth restriction, often assumed to be related to placental insufficiency, seem to be independent biologic entities.

In 1999, the US Food and Nutrition Board revised the Adequate Intake (AI) for calcium in pregnancy and recommended 1000 mg/day for adult pregnant women and 1300 mg/day for adolescent women (

Objective To determine whether intra-umbilical vein injection with saline solution, with or without oxytocin, reduces the need for manual removal of placenta compared with expectant management. Design Multicentre, randomised controlled trial. Setting Eleven hospitals in four cities of Argentina: Buenos Aires, Corrientes, Rosario, and Salta. Participants Two hundred and ninety-one women showing no evidence of placental separation thirty minutes after vaginal delivery. Interventions Three different management strategies: 1. intra-umbilical vein injection of saline solution plus oxytocin; 2. intra-umbilical vein injection of saline solution alone; and 3. expectant management. Main outcome measures Primary: manual removal of the placenta. Secondary: blood loss after trial entry, haemoglobin level at 24 to 48 hours and at 40 to 45 days after delivery, blood transfusion, curettage, infection, and days of hospital stay. Results Rates of subsequent manual removal were similar: intra-umbilical vein injection of saline solution plus oxytocin (58%; RR 0.92; 95% CI 0.73–1.15), or saline alone (63%; RR 1.00; 95% CI 0.80–1.24), compared with expectant management (63%). There were also no detectable effects of the active managements on any of the secondary measures of outcome. Conclusions Based on evidence available from randomised controlled trials, including this trial, it is unlikely that intra-umbilical injection with or without oxytocin, is clinically useful. We recommend that this intervention should not be used in third stage management of labour.

Summary Background We report the main findings of the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS), which aimed to assess the burden of complications related to pregnancy, the coverage of key maternal health interventions, and use of the maternal severity index (MSI) in a global network of health facilities. Methods In our cross-sectional study, we included women attending health facilities in Africa, Asia, Latin America, and the Middle East that dealt with at least 1000 childbirths per year and had the capacity to provide caesarean section. We obtained data from analysis of hospital records for all women giving birth and all women who had a severe maternal outcome (SMO; ie, maternal death or maternal near miss). We regarded coverage of key maternal health interventions as the proportion of the target population who received an indicated intervention (eg, the proportion of women with eclampsia who received magnesium sulphate). We used areas under the receiver operator characteristic curves (AUROC) with 95% CI to externally validate a previously reported MSI as an indicator of severity. We assessed the overall performance of care (ie, the ability to produce a positive effect on health outcomes) through standardised mortality ratios. Results From May 1, 2010, to Dec 31, 2011, we included 314 623 women attending 357 health facilities in 29 countries (2538 had a maternal near miss and 486 maternal deaths occurred). The mean period of data collection in each health facility was 89 days (SD 21). 23 015 (7·3%) women had potentially life-threatening disorders and 3024 (1·0%) developed an SMO. 808 (26·7%) women with an SMO had post-partum haemorrhage and 784 (25·9%) had pre-eclampsia or eclampsia. Cardiovascular, respiratory, and coagulation dysfunctions were the most frequent organ dysfunctions in women who had an SMO. Reported mortality in countries with a high or very high maternal mortality ratio was two-to-three-times higher than that expected for the assessed severity despite a high coverage of essential interventions. The MSI had good accuracy for maternal death prediction in women with markers of organ dysfunction (AUROC 0·826 [95% CI 0·802–0·851]). Interpretation High coverage of essential interventions did not imply reduced maternal mortality in the health-care facilities we studied. If substantial reductions in maternal mortality are to be achieved, universal coverage of life-saving interventions need to be matched with comprehensive emergency care and overall improvements in the quality of maternal health care. The MSI could be used to assess the performance of health facilities providing care to women with complications related to pregnancy. Funding UNDP–UNFPA–UNICEF–WHO–World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP); WHO; USAID; Ministry of Health, Labour and Welfare of Japan; Gynuity Health Projects.

Objective To assess the risks and benefits associated with caesarean delivery compared with vaginal delivery. Design Prospective cohort study within the 2005 WHO global survey on maternal and perinatal health. Setting 410 health facilities in 24 areas in eight randomly selected Latin American countries; 123 were randomly selected and 120 participated and provided data Participants 106 546 deliveries reported during the three month study period, with data available for 97 095 (91% coverage). Main outcome measures Maternal, fetal, and neonatal morbidity and mortality associated with intrapartum or elective caesarean delivery, adjusted for clinical, demographic, pregnancy, and institutional characteristics. Results Women undergoing caesarean delivery had an increased risk of severe maternal morbidity compared with women undergoing vaginal delivery (odds ratio 2.0 (95% confidence interval 1.6 to 2.5) for intrapartum caesarean and 2.3 (1.7 to 3.1) for elective caesarean). The risk of antibiotic treatment after delivery for women having either type of caesarean was five times that of women having vaginal deliveries. With cephalic presentation, there was a trend towards a reduced odds ratio for fetal death with elective caesarean, after adjustment for possible confounding variables and gestational age (0.7, 0.4 to 1.0). With breech presentation, caesarean delivery had a large protective effect for fetal death. With cephalic presentation, however, independent of possible confounding variables and gestational age, intrapartum and elective caesarean increased the risk for a stay of seven or more days in neonatal intensive care (2.1 (1.8 to 2.6) and 1.9 (1.6 to 2.3), respectively) and the risk of neonatal mortality up to hospital discharge (1.7 (1.3 to 2.2) and 1.9 (1.5 to 2.6), respectively), which remained higher even after exclusion of all caesarean deliveries for fetal distress. Such increased risk was not seen for breech presentation. Lack of labour was a risk factor for a stay of seven or more days in neonatal intensive care and neonatal mortality up to hospital discharge for babies delivered by elective caesarean delivery, but rupturing of membranes may be protective. Conclusions Caesarean delivery independently reduces overall risk in breech presentations and risk of intrapartum fetal death in cephalic presentations but increases the risk of severe maternal and neonatal morbidity and mortality in cephalic presentations.

Rates of cesarean section continue to increase throughout the world. The authors analyzed data from the 2005 World Health Organization global survey on maternal and perinatal health in an attempt to clarify the association between operative delivery and pregnancy outcome at the institutional level. The database consisted of a multistage stratified sample of 24 geographic regions in 8 Latin American countries. Data were collected for all women admitted to 120 institutions (randomly chosen from 410 hospitals) who were admitted for delivery over a 3-month period. Data were obtained for 97,095 of 106,546 deliveries-a coverage rate of 91%. The median rate of cesarean delivery was 33%. Factors that helped to determine operative delivery rates included primiparity, previous operative delivery, and institutional complexity. Private hospitals consistently had higher rates than did public institutions. After adjusting for risk factors, cesarean rates correlated positively with postpartum antibiotic treatment as well as with severe maternal morbidity and mortality. The most common indication for cesarean delivery was the spectrum of cephalopelvic disproportion/dystocia/failure to progress. Next most common in public hospitals was fetal distress and at private centers, previous cesarean delivery without complications. On multiple linear regression analysis, the only factors independently associated with cesarean delivery were primiparity, previous cesarean delivery, and institutional complexity. Only primiparity and previous cesarean delivery remained significant for elective operative deliveries. After adjusting for preterm delivery, an increased rate of cesarean delivery correlated with increased fetal mortality and more frequent admission of infants to intensive care for 1 week or longer. The frequency of preterm delivery and neonatal mortality increased when rates of cesarean delivery reached 10% to 20%. These findings indicate that a high cesarean delivery rate does not necessarily indicate good-quality care. Perinatal outcomes should be closely scrutinized at institutions where high operative delivery rates prevail.

The purpose of this trial was to determine whether calcium supplementation of pregnant women with low calcium intake reduces preeclampsia and preterm delivery.Randomized placebo-controlled, double-blinded trial in nulliparous normotensive women from populations with dietary calcium600 mg/d. Women who were recruited before gestational week 20 received supplements (1.5 g calcium/d or placebo) throughout pregnancy. Primary outcomes were preeclampsia and preterm delivery; secondary outcomes focused on severe morbidity and maternal and neonatal mortality rates.The groups comprised 8325 women who were assigned randomly. Both groups had similar gestational ages, demographic characteristics, and blood pressure levels at entry. Compliance were both 85% and follow-up losses (calcium, 3.4%; placebo, 3.7%). Calcium supplementation was associated with a non-statistically significant small reduction in preeclampsia (4.1% vs 4.5%) that was evident by 35 weeks of gestation (1.2% vs 2.8%; P = .04). Eclampsia (risk ratio, 0.68: 95% CI, 0.48-0.97) and severe gestational hypertension (risk ratio, 0.71; 95% CI, 0.61-0.82) were significantly lower in the calcium group. Overall, there was a reduction in the severe preeclamptic complications index (risk ratio, 0.76; 95% CI, 0.66-0.89; life-table analysis, log rank test; P = .04). The severe maternal morbidity and mortality index was also reduced in the supplementation group (risk ratio, 0.80; 95% CI, 0.70-0.91). Preterm delivery (the neonatal primary outcome) and early preterm delivery tended to be reduced among women who wereor = 20 years of age (risk ratio, 0.82; 95% CI, 0.67-1.01; risk ratio, 0.64; 95% CI, 0.42-0.98, respectively). The neonatal mortality rate was lower (risk ratio, 0.70; 95% CI, 0.56-0.88) in the calcium group.A 1.5-g calcium/day supplement did not prevent preeclampsia but did reduce its severity, maternal morbidity, and neonatal mortality, albeit these were secondary outcomes.

OBJECTIVE: Our aim was to document the differential neonatal morbidity and intrapartum and neonatal mortality of subgroups of preterm delivery. METHODS: This analysis included 38,319 singleton pregnancies, of which 3,304 (8.6%) were preterm deliveries (less than 37 completed weeks) enrolled in the World Health Organization randomized trial of a new antenatal care model. We classified them as preterm deliveries after spontaneous initiation of labor, either with or without maternal obstetric and medical complications; preterm deliveries after prelabor spontaneous rupture of amniotic membranes (PROM), either with or without obstetric and medical complications; and medically indicated preterm deliveries with maternal obstetric and medical complications. Severe neonatal morbidity and neonatal mortality were the primary outcomes. RESULTS: Fifty-six percent of all preterm deliveries were spontaneous, without maternal complications. Small for gestational age was increased only among the medically indicated preterm delivery group (22.3%). Very early preterm delivery (less than 32 weeks of gestation) was highest among PROM with complications (37%). For intrapartum fetal death and neonatal death, after adjusting by gestational age and other confounding variables, we found that the obstetric and medical complications preceding preterm delivery predicted the different risk levels. Conversely, for severe neonatal morbidity the clinical presentation, ie, PROM or medically indicated, predicted the increased risk. CONCLUSION: There are differential neonatal outcomes among preterm deliveries according to clinical presentation, pregnancy complications, gestational age at delivery, and its association with small for gestational age. This syndromic nature of the condition should be considered if preterm delivery is to be fully understood and thus reduced.

Objective The objective of the study was to examine whether blood pressure in early pregnancy and its rise in the second half of gestation are associated with spontaneous preterm birth in healthy, normotensive, nulliparous women. Study Design We included 5167 women with singleton gestation who participated in the World Health Organization Calcium Supplementation for the Prevention of Preeclampsia Trial. Systolic, diastolic, and mean arterial blood pressure and pulse pressure at baseline (12-19 weeks of gestation) and at the midthird trimester (30-34 weeks) were calculated. Rise in blood pressure was the difference between the midthird trimester and baseline. Preterm birth was defined as early preterm (less than 34 completed weeks) and late preterm birth (34-36 weeks). Results Women experiencing early or late preterm birth had over 10 mm Hg and 3 mm Hg higher rise, respectively, in systolic, diastolic, and mean arterial blood pressure than women delivering at term. A rise in systolic pressure over 30 mm Hg or diastolic pressure over 15 mm Hg was associated with a statistically significant 2- to 3-fold increase in risk of spontaneous preterm birth. Conclusion An excessive rise in either systolic or diastolic blood pressures from early pregnancy to the midthird trimester is associated with spontaneous preterm birth in a dose-response pattern.

Calcium supplementation has been reported to reduce blood pressure in pregnant and nonpregnant women. We undertook this prospective study to determine the effect of calcium supplementation on the incidence of hypertensive disorders of pregnancy (gestational hypertension and preeclampsia) and to determine the value of urinary calcium levels as a predictor of the response.We studied 1194 nulliparous women who were in the 20th week of gestation at the beginning of the study. The women were randomly assigned to receive 2 g per day of elemental calcium in the form of calcium carbonate (593 women) or placebo (601 women). Urinary excretion of calcium and creatinine was measured before calcium supplementation was begun. The women were followed to the end of their pregnancies, and the incidence of hypertensive disorders of pregnancy was determined.The rates of hypertensive disorders of pregnancy were lower in the calcium group than in the placebo group (9.8 percent vs. 14.8 percent; odds ratio, 0.63; 95 percent confidence interval, 0.44 to 0.90). The risk of these disorders was lower at all times during gestation, particularly after the 28th week of gestation (P = 0.01 by life-table analysis), in the calcium group than in the placebo group, and the risk of both gestational hypertension and preeclampsia was also lower in the calcium group. Among the women who had low ratios of urinary calcium to urinary creatinine (less than or equal to 0.62 mmol per millimole) during the 20th week of gestation, those in the calcium group had a lower risk of hypertensive disorders of pregnancy (odds ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09) and less of an increase in diastolic and systolic blood pressure than the placebo group. The pattern of response was similar among the women who had a high ratio of urinary calcium to urinary creatinine during the 20th week of gestation, but the differences were smaller.Pregnant women who receive calcium supplementation after the 20th week of pregnancy have a reduced risk of hypertensive disorders of pregnancy.