Calcium supplementation commencing before or early in pregnancy, or food fortification with calcium, for preventing hypertensive disorders of pregnancy

Background Pre-eclampsia is considerably more prevalent in low- than high-income countries. One possible explanation for this discrepancy is dietary diKerences, particularly calcium deficiency. Calcium supplementation in the second half of pregnancy reduces the serious consequences of pre-eclampsia and is recommended by the WorldHealthOrganization (WHO) for women with low dietary calcium intake, but has limited eKect on the overallrisk of pre-eclampsia. It is important to establish whether calcium supplementation before and in early pregnancy has added benefit. Such evidence would be justification for population-level fortification of staple foods with calcium. Objectives To determine the eKect of calcium supplementation or food fortification with calcium, commenced before or early in pregnancy and continued at least until mid-pregnancy, on pre-eclampsia and other hypertensive disorders, maternal morbidity and mortality, as well as fetal and neonatal outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Trials Register (10 August 2017), PubMed (29 June 2017), ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 August 2017) and reference lists of retrieved studies. Selection criteria Randomised controlled trials of calcium supplementation orfood fortification which include women of child bearing age not yet pregnant, or in early pregnancy. Cluster-RCTs, quasi-RCTs and trials published in abstract form only would have been eligible for inclusion in this review but none were identified. Cross-over designs are not appropriate for this intervention. The scope of this review is to consider interventions including calcium supplementation with or without additional supplements or treatments, compared with placebo or no intervention. Data collection and analysis Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Main results This review is based on one RCT (involving 60 women) which looked at calcium plus additional supplements versus control. The women (who had lowantioxidant status)were in the early stages of pregnancy.We did notidentify any studieswhere supplementation commenced pre-pregnancy. Another RCT comparing calcium versus placebo is ongoing but not yet complete. We did not identify any studies looking at any of our other planned comparisons. Calcium plus antioxidants and other supplements versus placebo We included one small study (involving 60 women with low antioxidantlevels) which was conducted in an academic hospital in Indondesia. The study was at low risk of bias for all domains with the exception of selective reporting, for which it was unclear. Women in the intervention group received calcium (800 mg) plus N-acetylcysteine (200 mg), Cu (2 mg), Zn (15 mg), Mn (0.5 mg) and selenium (100 mcg) and vitamins A (1000 IU), B6 (2.2 mg), B12 (2.2 mcg), C (200 mg), and E (400 IU) versus the placebo control group of women who received similar looking tablets containing iron and folic acid. Both groups received iron (30 mg) and folic acid (400 mcg). Tablets were taken twice daily from eight to 12 weeks of gestation and then throughout pregnancy. The included study found that calcium supplementation plus antioxidants and other supplements may slightly reduce pre-eclampsia (gestational hypertension and proteinuria) (risk ratio (RR) 0.24, 95% confidence interval (CI) 0.06 to 1.01; low-quality evidence), but this is uncertain due to wide confidence intervals just crossing the line of no eKect, and small sample size. It appears that earlypregnancy loss before 20 weeks' gestation (RR 0.06, 95% CI 0.00 to 1.04; moderate-quality evidence) may be slightly reduced by calcium plus antioxidants and other supplements, but this outcome also has wide confidence intervals, which just cross the line of no eKect. Very few events were reported under the composite outcome, severe maternal morbidity and mortality index and no clear diKerence was seen between groups (RR 0.36, 95% CI 0.04 to 3.23; low-quality evidence). However, the included study observed a reduction in the composite outcome pre-eclampsia and/or pregnancy loss at any gestational age (RR 0.13, 95% CI 0.03 to 0.50; moderate-quality evidence), and pregnancy loss/stillbirth at any gestational age (RR 0.06, 95% CI 0.00 to 0.92;moderate-quality evidence)in the calcium plus antioxidant/supplement group. Other outcomes reported (placental abruption, severe pre-eclampsia and preterm birth (less than 37 weeks' gestation)) were too infrequent for meaningful analysis. No data were reported for the outcomes caesarean section, birthweight less 2500 g, Apgar score less than seven at five minutes, death or admission to neonatal intensive care unit (ICU), or pregnancy loss, stillbirth or neonatal death before discharge from hospital. Authors' conclusions The results of this review are based on one small study in which the calcium intervention group also received antioxidants and other supplements. Therefore, we are uncertain whether any of the eKects observed in the study were due to calcium supplementation or not. The evidence in this review was graded low to moderate due to imprecision. There is insuKicient evidence on the eKectiveness or otherwise of pre- or early-pregnancy calcium supplementation, or food fortification for preventing hypertensive disorders of pregnancy. Furtherresearch is needed to determine whether pre- or early-pregnancy supplementation, orfood fortification with calcium is associated with a reduction in adverse pregnancy outcomes such as pre-eclampsia and pregnancy loss. Such studies should be adequately powered, limited to calcium supplementation, placebo-controlled, and include relevant outcomes such as those chosen for this review. There is one ongoing study of calcium supplementation alone versus placebo and this may provide additional evidence in future update

Fundal pressure during the second stage of labour

Background Fundal pressure during the second stage of labour (also known as the 'Kristeller manoeuvre') involves application of manual pressure to the uppermost part of the uterus directed towards the birth canal, in an attempt to assist spontaneous vaginal birth and avoid prolonged second stage orthe need for operative birth. Fundal pressure has also been applied using an inflatable belt. Fundal pressure is widely used, however methods of its use vary widely. Despite strongly held opinions in favour of and against the use of fundal pressure, there is limited evidence regarding its maternal and neonatal benefits and harms. There is a need for objective evaluation of the eGectiveness and safety of fundal pressure in the second stage of labour. Objectives To determine if fundal pressure is eGective in achieving spontaneous vaginal birth, and preventing prolonged second stage or the need for operative birth, and to explore maternal and neonatal adverse eGects related to fundal pressure. Search methods We searched Cochrane Pregnancy and Childbirth's Trials Register (30 November 2016) and reference lists of retrieved studies. Selection criteria Randomised and quasi-randomised controlled trials of fundal pressure (manual or by inflatable belt) versus no fundal pressure in women in the second stage of labour with singleton cephalic presentation. Data collection and analysis Two or more review authors independently assessed potential studies for inclusion and quality. We extracted data using a pre-designed form. We entered data into Review Manager 5 soAware and checked for accuracy. Main results Nine trials are included in this updated review. Five trials (3057 women) compared manual fundal pressure versus no fundal pressure. Four trials (891 women) compared fundal pressure by means of an inflatable belt versus no fundal pressure. It was not possible to blind women and staG to this intervention. We assessed two trials as being at high risk of attrition bias and another at high risk of reporting bias. All other trials were low or unclear for other risk of bias domains. Most of the trials had design limitations. Heterogeneity was high for the majority of outcomes. Manual fundal pressure versus no fundal pressure Manual fundal pressure was not associated with changes in: spontaneous vaginal birth within a specified time (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.71 to 1.28; 120 women; 1 trial; very low-quality evidence), instrumental births (RR 3.28, 95% CI 0.14 to 79.65; 197 women; 1 trial), caesarean births (RR 1.10, 95% CI 0.07 to 17.27; 197 women; 1 trial), operative birth (average RR 0.66, 95% CI 0.12 to 3.55; 317 women; 2 studies; I2 = 43%; Tau2 = 0.71; very low-quality evidence), duration of second stage (mean diGerence (MD) -0.80 minutes, 95% CI -3.66 to 2.06 minutes; 194 women; 1 study; very low-quality evidence), low arterial cord pH in newborn babies (RR 1.07, 95% CI 0.72 to 1.58; 297 women; 2 trials; very low-quality evidence), or Apgar scores less than seven at five minutes (average RR 4.48, 95% CI 0.28 to 71.45; 2759 infants; 4 trials; I2 = 89%; Tau2 = 3.55; very low-quality evidence). More women who received manual fundal pressure had cervical tears than in the control group (RR 4.90, 95% CI 1.09 to 21.98; 295 women; 1 trial). No neonatal deaths occurred in either of the two studies reporting this outcome (very low-quality evidence). No trial reported the outcome severe maternal morbidity or death. Fundal pressure by inflatable belt versus no fundal pressure Fundal pressure by inflatable belt did not reduce the number of women havinginstrumental births (average RR 0.73, 95% CI 0.52 to 1.02; 891 women; 4 trials; I2 = 52%; Tau2 = 0.05) or operative births (average RR 0.62, 95% CI 0.38 to 1.01; 891 women; 4 trials; I2 = 78%; Tau2 = 0.14; very low-quality evidence). Heterogeneity was high for both outcomes. Duration of second stage was reported in two trials, which both showed that inflatable belts shortened duration of labour in nulliparous women (average MD -50.80 minutes, 95% CI -94.85 to -6.74 minutes; 253 women; 2 trials; I2 = 97%; Tau2 = 975.94; very low-quality evidence). No data on this outcome were available for multiparous women. The inflatable belt did not make any diGerence to rates of caesarean births (average RR 0.56, 95% CI 0.14 to 2.26; 891 women; 4 trials; I2 = 70%; Tau2 = 0.98), low arterial cord pHin newborn babies (RR 0.47, 95% CI 0.09 to 2.55; 461 infants; 1 trial; low-quality evidence), or Apgar scores less than seven atfive minutes (RR 4.62, 95% CI 0.22 to 95.68; 500 infants; 1 trial; very low-quality evidence). Third degree perinealtears were increased in the inflatable belt group (RR 15.69, 95% CI 2.10 to 117.02; 500 women; 1 trial). Spontaneous vaginal birth within a specified time, neonatal death, andsevere maternal morbidity or death were not reported in any trial. Authors' conclusions There is insuGicient evidence to draw conclusions on the beneficial or harmful eGects of fundal pressure, either manually or by inflatable belt. Fundal pressure by an inflatable belt during the second stage of labour may shorten duration of second stage for nulliparous women, and lower rates of operative birth. However, existing studies are small and their generalizability is uncertain. There is insuGicient evidence regarding safety for the baby. There is no evidence on the use of fundal pressure in specific clinical settings such as inability of the mother to bear down due to exhaustion or unconsciousness. There is currently insuGicient evidence for the routine use of fundal pressure by any method on women in the second stage of labour. Because of current widespread use of the procedure and the potential for use in settings where other methods of assisted birth are not available, further good quality trials are needed. Further evaluation in other groups of women (such as multiparous women) will also be required. Future research should describe in detail how fundal pressure was applied and consider safety of the unborn baby, perineal outcomes, longer-term maternal and infant outcomes and maternal satisfaction