Prepregnancy and early pregnancy calcium supplementation among women at high risk of pre-eclampsia: a multicentre, double-blind, randomised, placebo-controlled trial

Hofmeyr, G Justus; Fawcus, Susan; Roberts, James M.; Althabe, Fernando; Belizán, José M.; Bergel, Eduardo; Ciganda, Álvaro; Cormick, Gabriela; Sawchuck, Diane; Vidler, Marianne; Allie, Saadiqa; Anthony, John; Frank, Karlyn; Greeff, A; Fawcus, Sue; Hall, David; Hofmeyr, Justus; Kovane, Mvuseleli; Kovane, Patience; Lawrie, Theresa A; Mose, Simpiwe; Mshweshwe, Nolundi; Mqikela, Velisa; Njikelana, Pamela; Novikova, Natalia; Oyebajo, Adegboyega; Parker, Charla A.; Phuti, Angel; Singata‐Madliki, Mandisa; Papendorp, Erika van; Williams, Xoliswa; Betrán, Ana Pilar; Dannemann, Tina; Seuc, Armando; Magee, Laura A.; Dadelszen, Peter von; Donnay, F; Drebit, Sharla; Roberts, Jim; Guzha, Bothwell Takaingofa; Makaza, Emilia; Manyame, Sarah; Munjanja, Stephen; Tahuringana, Eunice

doi:10.1016/s0140-6736(18)31818-x

Cited by 107 publications

(102 citation statements)

References 23 publications

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“…16 In addition, results from a recent randomised trial suggest that the beneficial effects of calcium supplementation on the reduction of preeclampsia/eclampsia in women with low dietary calcium intake is greatest when supplementation is commenced before and continued throughout pregnancy. 17 The mechanism by which calcium may have an effect on blood pressure is not well established; one hypothesis is that low calcium intakes increase the levels of parathyroid hormone and 1,25-dihydroxy vitamin D (DHVD), which are required to maintain specific calcium concentrations in extracellular fluids. Higher levels of parathyroid hormone and DHVD stimulate calcium influx into different cell types and increase intracellular calcium into the vascular smooth muscle cell, and consequently increased muscle reactivity, peripheral vascular resistance, and thus higher blood pressure.…”

Section: Introductionmentioning

confidence: 99%

Global inequities in dietary calcium intake during pregnancy: a systematic review and meta‐analysis

Cormick

Betrán

Romero

et al. 2018

BJOG

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Background Evidence shows that adequate calcium intake during pregnancy reduces the risk of hypertensive disorders of pregnancy. In most low‐ and middle‐income countries ( LMIC s) the daily calcium intake is well below recommendations. Mapping calcium intake during pregnancy worldwide and identifying populations with low calcium intake will provide the evidence base for more targeted actions to improve calcium intake. Objective To assess dietary calcium intake during pregnancy worldwide. Search strategy MEDLINE and EMBASE (from July 2004 to November 2017). Selection criteria Cross‐sectional, cohort, and intervention studies reporting calcium intake during pregnancy. Data collection and analysis Five reviewers working in pairs independently performed screening, extraction, and quality assessment. We reported summary measures of calcium intake and calculated the weighted arithmetic mean for high‐income countries ( HIC s) and LMIC s independently, and for geographic regions, among studies reporting country of recruitment, mean intake, and total number of participants. When available, inadequate intakes were reported. Main results From 1880 citations 105 works met the inclusion criteria, providing data for 73 958 women in 37 countries. The mean calcium intake was 948.3 mg/day (95% CI 872.1–1024.4 mg/day) for HIC s and 647.6 mg/day (95% CI 568.7–726.5 mg/day) for LMIC s. Calcium intakes below 800 mg/day were reported in five (29%) countries from HIC s and in 14 (82%) countries from LMIC s. Conclusion These results are consistent with a lack of improvement in calcium dietary intake during pregnancy and confirm the gap between HIC s and LMIC s, with alarmingly low intakes recorded for pregnant women in LMIC s. From the public health perspective, in the absence of specific local data, calcium supplementation of pregnant women in these countries should be universal. Tweetable abstract Despite dietary recommendations, women in LMIC s face pregnancy with diets low in calcium.

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Section: Introductionmentioning

confidence: 99%

Global inequities in dietary calcium intake during pregnancy: a systematic review and meta‐analysis

Cormick

Betrán

Romero

et al. 2018

BJOG

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“…These trials generally involved women who were in the later part of their gestational age. For instance, only 5 trials enrolled women from or before conception (Owens 46 , The women First Trial 47 , CAP Trial 48 , PRECONCEPT 49 , and Brabin 50 ), while the majority of trials recruited women who were in the later trimesters, such as the 2 nd and 3 rd trimesters (n = 69 trials).…”

Section: Resultsmentioning

confidence: 99%

Interventions to improve birth outcomes of pregnant women living in low- and middle-income countries: a systematic review and network meta-analysis

Park

Harari²,

Siden

et al. 2020

Gates Open Res

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Background: Improving the health of pregnant women is important to prevent adverse birth outcomes, such as preterm birth and low birthweight. We evaluated the comparative effectiveness of interventions under the domains of micronutrient, balanced energy protein, deworming, maternal education, and water sanitation and hygiene (WASH) for their effects on these adverse birth outcomes. Methods: For this network meta-analysis, we searched for randomized clinical trials (RCTs) of interventions provided to pregnant women in low- and middle-income countries (LMICs). We searched for reports published until September 17, 2019 and hand-searched bibliographies of existing reviews. We extracted data from eligible studies for study characteristics, interventions, participants’ characteristics at baseline, and birth outcomes. We compared effects on preterm birth (<37 gestational week), low birthweight (LBW; <2500 g), and birthweight (continuous) using studies conducted in LMICs. Results: Our network meta-analyses were based on 101 RCTs (132 papers) pertaining to 206,531 participants. Several micronutrients and balanced energy food supplement interventions demonstrated effectiveness over standard-of-care. For instance, versus standard-of-care, micronutrient supplements for pregnant women, such as iron and calcium, decreased risks of preterm birth (iron: RR=0.70, 95% credible interval [Crl] 0.47, 1.01; calcium: RR=0.76, 95%Crl 0.56, 0.99). Daily intake of 1500kcal of local food decreased the risks of preterm birth (RR=0.36, 95%Crl 0.16, 0.77) and LBW (RR=0.17, 95%Crl 0.09, 0.29), respectively when compared to standard-of-care. Educational and deworming interventions did not show improvements in birth outcomes, and no WASH intervention trials reported on these adverse birth outcomes. Conclusion: We found several pregnancy interventions that improve birth outcomes. However, most clinical trials have only evaluated interventions under a single domain (e.g. micronutrients) even though the causes of adverse birth outcomes are multi-faceted. There is a need to combine interventions that of different domains as packages and test for their effectiveness. Registration: PROSPERO CRD42018110446; registered on 17 October 2018.

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“…These interventions address the different pathogenesis possibly involved in preeclampsia. These include calcium, vitamin C and E supplementation, or Aspirin prescription, which has been suggested to efficiently prevent preeclampsia among women at high risk [14][15][16], specifically in preterm preeclampsia and if initiated early in pregnancy. Additional treatments include medications to prevent hypertension and seizures [15,17].…”

Section: Introductionmentioning

confidence: 99%

Who Is at Risk for Preeclampsia? Risk Factors for Developing Initial Preeclampsia in a Subsequent Pregnancy

Wainstock

Sergienko

2020

JCM

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Background: The incidence of preeclampsia, which may cause significant maternal and perinatal morbidity, has risen in recent years, therefore it is critical to identify women at risk for preeclampsia. We aimed to identify risk factors in the first pregnancy (not complicated by preeclampsia) for preeclampsia in the subsequent pregnancy. Methods: A retrospective population-based nested case-control study was conducted, including all women with first (P1) and second (P2) singleton consecutive deliveries. Women who had experienced preeclampsia in their first pregnancy were excluded. Cases were defined as women with preeclampsia in their second pregnancy, and were compared to the controls, defined as women without this diagnosis in second pregnancy. Characteristics and complications of the first pregnancy were compared between cases and controls, and multivariable regression models were used to study the association between pregnancy complications (in the first pregnancy) and preeclampsia (in the subsequent pregnancy), while adjusting for confounders. Results: A total of 40,673 women were included in the study, 1.5% of second pregnancies were diagnosed with preeclampsia (n = 627, i.e., Cases). Cases, as compared to controls were older in their 1st pregnancy, with longer inter-pregnancy interval, and were more likely to have the following complications in their first pregnancy: preterm delivery (15.0% vs. 7.7%), low birthweight (17.9% vs. 10.3%), perinatal mortality (3.2% vs. 1.1%), and gestational diabetes (7.0% vs. 2.7%). In the multivariable model, adjusted for maternal age, obesity and inter-pregnancy interval, either one of these first pregnancy complications were independently associated with an increased risk for preeclampsia (adjusted OR for either of first pregnancy complication =1.73; 95% CI 1.37–2.14, <0.001), and the risk was greater for each additional complication (adjusted OR for ≥2 risk factors =3.54; 95% CI 2.28–5.52, p < 0.001). Conclusions: Complications in first pregnancy, including preterm delivery, perinatal mortality and gestational diabetes, are risk factors for primary preeclampsia in second pregnancy. First pregnancy may serve as a window of opportunity to identify women at risk for future preeclampsia and other morbidities later in life.

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Prepregnancy and early pregnancy calcium supplementation among women at high risk of pre-eclampsia: a multicentre, double-blind, randomised, placebo-controlled trial

Cited by 107 publications

References 23 publications

Global inequities in dietary calcium intake during pregnancy: a systematic review and meta‐analysis

Global inequities in dietary calcium intake during pregnancy: a systematic review and meta‐analysis

Interventions to improve birth outcomes of pregnant women living in low- and middle-income countries: a systematic review and network meta-analysis

Who Is at Risk for Preeclampsia? Risk Factors for Developing Initial Preeclampsia in a Subsequent Pregnancy

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