Effect of folic acid supplementation during pregnancy on gestational hypertension/preeclampsia: A systematic review and meta-analysis

Objective: To evaluate the effect of folic acid supplementation during pregnancy on the risk of gestational hypertension/preeclampsia. Methods: A systematic review and meta-analysis were conducted. Medline, Embase, Scopus, and the Web of Science were searched from inception to December 2014. Results: Out of 1224 potentially relevant studies, 13 studies met our inclusion criteria (2 randomized controlled trials (RCTs), 10 cohort studies, and 1 case–control study). The pooled relative risk (RR) and 95% confidence interval (CI) of the two RCTs were 0.62 (0.45–0.87) in the trial arm as compared with the placebo arm. The pooled RR was 0.92 (95% CI: 0.79–1.08) for nine cohort studies with available data on folic acid supplementation in pregnancy and gestational hypertension/preeclampsia. Pooled RR was 0.88 (95% CI: 0.76–1.02) for eight cohort studies with available data on folic acid supplementation and preeclampsia. Conclusion: Whether folic acid supplementation in pregnancy can prevent the occurrence of gestational hypertension/preeclampsia remains uncertain.     

Is low-dose aspirin therapy to prevent preeclampsia more efficacious in non-obese women or when initiated early in pregnancy?

Objective: Late timing of intervention and maternal obesity are potential explanations for the modest effect of aspirin for preeclampsia prevention. We explored whether low-dose aspirin (LDA) is more effective in women at increased risk when initiated before 16 weeks' gestation or given to non-obese women.

Methods: Secondary analysis of a trial to evaluate LDA (60?mg/d) for preeclampsia prevention in high-risk women. Participants were randomized to LDA or placebo between 13 and 26 weeks. We stratified the effect of LDA on preeclampsia by (a) timing of randomization (Results: Of 2503 women, 461 (18.4%) initiated LDA?p value for interaction?=?0.87). Similarly, LDA effect was not better in non-obese (RR: 0.91, 95% CI: 0.7–1.13) versus obese women (RR: 0.89, 95% CI: 0.7–1.13), (p value for interaction?=?0.85).

Conclusion: LDA for preeclampsia prevention was not more effective when initiated 相似文献   

A Meta-Analysis on the Efficacy and Safety of Combined Vitamin C and E Supplementation in Preeclamptic Women

Objective: To evaluate whether vitamin C and E co-supplementation of women at risk of preeclampsia can reduce maternal and neonatal disorders. Method: Electronic databases were searched up to May 2008 to find studies investigating pregnancy outcomes in women at risk of preeclampsia following exposure to combined vitamin C and E supplementation. The outcomes of interest were gestational hypertension, preeclampsia, preterm delivery, small for gestational age, and low birth weight. The relative risk (RR) and confidence interval (CI) for the individual studies were pooled and heterogeneity analysis was performed. Results: Seven studies involving 5969 pregnant women at risk of preeclampsia were included: 2982 received vitamin C and E and 2987 received placebo. The RRs are 1.3 (95% CI of 1.08–1.57, p = 0.0066) for gestational hypertension, 0.7 (95% CI of 0.58–1.08, P = 0.1653) for preeclampsia, 1.12 (95% CI of 0.96–1.32, p = 0.141) for preterm delivery, 1.04 (95% CI of 0.94–1.15, p = 0.4789) for small for gestational age, and 1.13 (95% CI of 1.004–1.27, p = 0.0429) for low birth weight. Conclusion. Combined vitamin C and E supplementation not only have no potential benefit in improvement of maternal and neonatal outcome but increase the risk of gestational hypertension in women at risk of preeclampsia and low birth weight in neonates.     

Acetylsalicylic Acid for the Prevention of Preeclampsia and Intra-uterine Growth Restriction in Women with Abnormal Uterine Artery Doppler: A Systematic Review and Meta-analysis

BackgroundPreeclampsia is a major global cause of maternal, neonatal and perinatal mortality. From studies of placental pathophysiology in women with preeclampsia, a potentially important role of low-dose acetylsalicylic acid (ASA) in the prevention of preeclampsia was expected, but the results from clinical trials have been disappointing. While recent evidence has shown that uterine Doppler can predict preeclampsia as early as in the first trimester of pregnancy, most clinical trials have evaluated ASA in the second and third trimesters.ObjectivesWe performed a meta-analysis to assess the influence of gestational age at the time of introduction of ASA on the incidence of preeclampsia in women at increased risk, on the basis of abnormal uterine artery Doppler.MethodsComputerized searches of randomized controlled trials were conducted to retrieve studies in which pregnant women at increased risk of preeclampsia had been identified on the basis of abnormal uterine Doppler measurements. The trials compared women who received ASA with a control group. The primary outcome was preeclampsia. Secondary outcomes included severe preeclampsia, gestational hypertension, preterm birth, intrauterine growth restriction, placental abruption, birth weight and gestational age at delivery. Statistical analyses used fixed effects of risk ratio (RR) with the Mantel-Haenszel method and 95% confidence intervals.ResultsNine randomized controlled trials with a total of 1317 women met the inclusion criteria. ASA treatment beginning in early gestation was associated with a greater reduction in the incidence of preeclampsia than treatment beginning in late gestation: ASA treatment started at ≤16 weeks’ gestation resulted in RR 0.48 (95% CI 0.33 to 0.68), at 17–19 weeks RR 0.55 (95% CI 0.17 to 1.76), and at ≥ 20 weeks RR 0.82 (95% CI 0.62 to 1.09). ASA treatment started before 16 weeks was also linked with a significant reduction in the incidence of severe preeclampsia (RR 0.10; 95% CI 0.01 to 0.74), gestational hypertension (RR 0.31; 95% CI 0.13 to 0.78) and IUGR (RR 0.51; 95% CI 0.28 to 0.92).ConclusionASA treatment initiated early in pregnancy is an efficient method of reducing the incidence of preeclampsia and its consequences in women with ultrasonographic evidence of abnormal placentation diagnosed by uterine artery Doppler studies.     

Calcium supplementation in nulliparous women for the prevention of pregnancy-induced hypertension, preeclampsia and preterm birth: an Australian randomized trial. FRACOG and the ACT Study Group

A multicentre, randomized controlled double-blind trial in 5 maternity hospitals in Australia assessed the effect of a daily supplement of calcium (1.8g oral calcium or an oral placebo) taken daily until delivery, from less than 24 weeks' gestation, on the frequency of pregnancy-induced hypertension, preeclampsia and preterm birth (< 37 weeks' gestation) in 456 nulliparas with a singleton pregnancy. Treatment with calcium reduced the risk of preeclampsia (relative risk 0.44 [95% CI, 0.21-0.90], p = 0.02) and the risk of preterm birth (relative risk 0.44 [95% CI, 0.21-0.90], p = 0.02). No significant differences were seen between the 2 groups in the frequency of pregnancy-induced hypertension, although the study only had statistical power to detect large differences in this outcome. An updated systematic review of the 9 randomized trials of calcium supplementation in pregnancy shows a significant reduction in the risk of hypertension and preeclampsia although no effect on preterm birth. Calcium supplementation during pregnancy reduced the risk of preeclampsia and preterm birth in this nulliparous population. The available evidence for systematic review of all the randomized trials of calcium supplementation shows benefit in reducing the risk of hypertension and preeclampsia.     

Crack abuse during pregnancy: maternal,fetal and neonatal complication

Objective: The aim of this study was to assess the effects of crack on pregnancy outcomes.

Methods: We studied 88 crack user pregnant women in this study. These women were matched to a drug-free group (n?=?90) chosen from the population of the same hospital. Maternal outcomes including preeclampsia, placenta abruption, gestational diabetes and preterm labor, and neonatal complication including low birth weight and low Apgar score in 5?min were compared in crack using and drug-free groups. Data were analyzed by SPSS software. Chi-square test and Student’s t-test and Relative Risks (RRs) were used in this study.

Results: The results of our study showed that crack abuse during pregnancy was associated with higher rate of preeclampsia p?=?0.003 (RR, 1.731; 95% CI, 1.777–2.545), placental abruption p?=?0.001 (RR, 2.439; 95% CI, 1.369–4.343), preterm labor p?<?0.000 (RR, 3.249; 95% CI, 2.053–5.141) and low birth weight p?<?0.000 (RR, 2.179; 95% CI, 1.462–3.247).

Conclusions: Crack abuse had significant influence on pregnancy outcomes. Crack appears to influence the prevalence of low birth weight, preterm labor, preeclampsia and placental abruption.     

Aspirin or heparin or both in the treatment of recurrent spontaneous abortion in women with antiphospholipid antibody syndrome: a meta-analysis of randomized controlled trials

Objective: This study was designed to evaluate the efficacy of aspirin or heparin or both in the treatment for recurrent spontaneous abortion (RSA) in women with antiphospholipid antibody syndrome (APS).

Methods: Systematic searches for randomized clinical trials (RCTs) evaluating on live birth and preterm delivery, preeclampsia, intrauterine growth restriction, gestational diabetes, bleeding of RSA with APS patients receiving aspirin, and heparin therapy were carried out, from PubMed, EMBASE, ScienceDirect, and CNKI. Related data were extracted from eligible studies and then subjected to Reviewer Manage 5.3 for analysis. Relative risk (RR) and its 95% confidence interval were calculated.

Results: Nineteen publications with randomized controlled trials were selected for this study, which included a total of 1251 pregnant patients with diagnosis of RSA with APS. With respect to live birth, it was remarkably improved in aspirin plus heparin or heparin alone group [RR?=1.23, 95% CI (1.12–1.36), p?p?=?.02]; aspirin alone group, however, there was no statistically significant difference compare to placebo [RR?=?0.97, 95% CI (0.80–1.16), p?=?.71]. Meanwhile, aspirin plus heparin therapy did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications including preterm birth, intrauterine growth retardation (IUGR), gestational diabetes, and minor bleeding. A beneficial therapeutic effect of heparin alone therapy was found on preventing preterm birth and low-dose aspirin plus heparin therapy was significant reduce the risk of preeclampsia.

Conclusion: An improvement of pregnancy outcomes in women with RSA and APS can be achieved by treatment strategies combining low-dose aspirin plus heparin or heparin alone. Aspirin alone, by contrast, seemed inferior to other treatments in achieving more live birth.     

Combined vitamin C and E supplementation during pregnancy for preeclampsia prevention: a systematic review

The effect of combined vitamin C and E supplementation during pregnancy on the prevention of preeclampsia and major adverse infant outcomes has been reviewed. We searched MEDLINE and the Central Library of Controlled Trials of the Cochrane Library through August 2006 for relevant clinical trials. Interstudy heterogeneity was evaluated using the chi(2) statistic (Q statistic) test. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with a fixed or random-effects model as appropriate. Four trials that collectively randomized 4680 pregnant women to either the combination of vitamin C and vitamin E or placebo were included in the analysis. There were no significant differences between the vitamin and placebo groups in the risk of preeclampsia, 11% versus 11.4%, RR 0.97 (95% CI 0.82-1.13), fetal or neonatal loss, 2.6% versus 2.3%, RR 1.10 (95% CI 0.78-1.57), or small for gestational age (SGA) infant, 20.6% versus 20%, RR 0.94 (95% CI 0.74-1.19). Although there was a higher risk for preterm birth in the vitamin group, 19.5% versus 18%, RR 1.07 (95% CI 0.96-1.20), this finding was not significant. Combined vitamin C and E supplementation during pregnancy does not reduce the risk of preeclampsia, fetal or neonatal loss, small for gestational age infant, or preterm birth. Such supplementation should be discouraged unless solid supporting data from randomized trials become available. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall that many methods have been used to prevent preeclampsia, state that increased oxidative stress has been postulated and many trials have used antioxidants to prevent the disease, and explain that MEDLINE analysis of the literature questions the use of vitamin C and E supplements.     

Calcium supplementation and prevention of preeclampsia: a meta-analysis

Background: Since the early 1980s, epidemiological evidence has suggested a connection between low calcium intake and preeclampsia The purpose of this meta-analysis is to summarize current evidence regarding calcium supplementation during pregnancy in predicting preeclampsia and associated maternal–fetal complications. Methods: Literature revision of all RCT (random allocation of calcium versus placebo) available in MEDLINE/PUBMED up to 2/29/2012 regarding calcium supplementation during pregnancy for preventing preeclampsia. We used the Mantel-Haenszel’s Method for four subgroup of patients: Adequate calcium intake; Low calcium intake; Low risk of preeclampsia; High risk of preeclampsia. We considered p < 0.05 as significant. Results: There is no consensus in Literature about: (1) the efficacy of calcium supplementation in the prevention of preeclampsia, (2) other/adverse/long-term effects of calcium supplementation in pregnancy. Conclusions: Preeclampsia is likely to be a multifactorial disease. However, inadequate calcium intake represents a factor associated with an increased incidence of hypertensive disease. The results of our meta-analysis demonstrate that the additional intake of calcium during pregnancy is an effective measure to reduce the incidence of preeclampsia, especially in populations at high risk of preeclampsia due to ethnicity, gender, age, high BMI and in those with low baseline calcium intake.     

Effects of prenatal micronutrient supplementation on complications of labor and delivery and puerperal morbidity in rural Nepal

Objective

To examine the effect of supplemental prenatal folic acid, folic acid-iron, folic acid-iron-zinc, and multiple micronutrients on maternal morbidity in rural Nepal.

Methods

A cluster-randomized double-masked controlled trial of pregnant women who received daily supplements from early pregnancy through 3 months post partum as per the treatment allocation. Women were interviewed at birth about labor and delivery complications and for 9 days post partum to obtain 24-hour histories of morbidity.

Results

A total of 3986 (97.3%) women completed an interview regarding labor and delivery; morbidity history was available for 3564 (87.0%) women. Folic acid-iron reduced the risk of postpartum hemorrhage (relative risk [RR] 0.59; 95% confidence interval [CI] 0.35-0.98). Risk of dysfunctional labor increased with multiple micronutrient supplementation (RR 1.28; 95% CI, 1.01-1.60), although preterm premature rupture of membrane decreased (RR 0.40; 95% CI, 0.21-0.79). Puerperal sepsis was lower in those receiving folic acid-iron, folic acid-iron-zinc, and multiple micronutrients compared with controls (P < 0.05).

Conclusion

Prenatal folic acid-iron supplementation reduced the risk of obstetric complications in this South Asian setting.     

5-Methyl-tetrahydrofolate in prevention of recurrent preeclampsia

Objective: To evaluate the efficacy of 5-methyl-tetrahydrofolate (5-MTHF) supplementation in prevention of recurrent preeclampsia.

Methods: Retrospective cohort of women who received daily oral 5-MTHF 15?mg supplementation as prophylactic treatment since first trimester for recurrent preeclampsia were compared with women who did not. All asymptomatic singleton gestations with prior preeclampsia (in the previous pregnancy) were included. Women with chronic hypertension were excluded. The primary outcome was the incidence of preeclampsia.

Results: Three hundred and three singleton gestation met the inclusion criteria: 157 received 5-MTHF, while 146 did not (control group). Women who received 5-MTHF had a significantly lower incidence of recurrent overall preeclampsia (21.7% versus 39.7%; odds ratio (OR) 0.57, 95% confidence interval (CI) 0.25, 0.69), severe preeclampsia (3.2% versus 8.9%; OR 0.44, 95% CI 0.12–0.97) and early-onset preeclampsia (1.9% versus 7.5%; OR 0.34, 95% CI 0.07–0.87) compared to control. The intervention group delivered about 10?d after the control and had higher birth weight.

Conclusion: This retrospective study showed that women with prior preeclampsia who received daily oral 5-MTHF 15?mg supplementation had a significantly lower incidence of overall preeclampsia, severe preeclampsia and early-onset preeclampsia. Randomized controlled trials are needed to confirm our findings.     

Preventing preeclampsia and its fetal complications with low-dose aspirin in East Asians and non-East Asians:A systematic review and meta-analysis

Background: Low-dose aspirin can reduce the incidence of preeclampsia and intrauterine growth restriction (IUGR). However, the effects of ethnicity upon low-dose aspirin’s efficacy has not been analyzed. Here, we comparatively evaluated the efficacy of low-dose aspirin in preventing preeclampsia and related fetal complications in East Asian and non-East Asian pregnant women at risk for preeclampsia. Methods: Several databases were searched for randomized controlled trials (RCTs) comparing low-dose aspirin with either placebo or no treatment in pregnant women at risk for preeclampsia. Odds ratios (ORs) and associated 95% confidence intervals (CIs) for preeclampsia and related fetal outcomes were tabulated. Results: Low-dose aspirin significantly reduced preeclampsia risk in both East Asians (OR = 0.20, 95% CI: 0.11–0.35) and non-East Asians (OR = 0.84, 95% CI: 0.77–0.92). Low-dose aspirin significantly reduced IUGR risk in East Asians (OR = 0.36, 95% CI: 0.20–0.67) but not in non-East Asians (OR = 0.85, 95% CI: 0.41–1.77). Low-dose aspirin did not significantly reduce the risk of cesarean section in either East Asians (OR = 0.67, 95% CI: 0.14–3.22) or non-East Asians (OR = 1.01, 95% CI: 0.86–1.19). Conclusions: Low-dose aspirin is effective in reducing preeclampsia risk in both East Asians and non-East Asians and has differential effects in East Asians and non-East Asians with respect to IUGR.     

Lower Rate of Preeclampsia After Antioxidant Supplementation in Pregnant Women with Low Antioxidant Status

Objective: To investigate maternal and neonatal outcomes after antioxidant supplementation relatively early in pregnancy (8 to 12 weeks) for pregnant women with low antioxidant status. Methods: A randomized, double-blind, placebo-controlled trial of daily antioxidant supplementation was performed on pregnant women screening positive for low antioxidant status at 8 to 12 weeks of gestation. Low antioxidant status was defined as a superoxidedismutase (SOD) level below 1102 U/g Hb or 164 U/mL. The supplementation group received the following antioxidants daily: vitamins A (1000 IU), B6 (2.2 mg), B12 (2.2 μg), C (200 mg), and E (400 IU), folic acid (400 μg), N-acetylcysteine (200 mg), Cu (2 mg), Zn (15 mg), Mn (0.5 mg), Fe (30 mg), calcium (800 mg), and selenium (100 μg). The control group received Fe (30 mg) and folic acid (400 μg). Maternal (preeclampsia, abortion, and hypertension) and perinatal outcomes were assessed. Results: In the supplementation group (29 subjects), we observed 2 cases of preeclampsia (6.8%, 1 mild and 1 severe), 1 of IUGR (birth weight 2300 g at 38 weeks), and 1 preterm delivery. In the control group (31 subjects), there were 8 abortions, 9 cases of preeclampsia (29%, 6 mild and 3 severe) with perinatal outcome: 3 preterm delivery cases and 1 IUGR (birth weight 2030 g at 39 weeks). Preeclampsia was significantly less frequent in the supplementation group when compared to the control group (2 vs. 9 cases, p = 0.043, OR = 0.18 [95% CI: 0.03, 0.92]). Finally we focused on the prediction of preeclampsia at 8 to 12 weeks. Combined sensitivity of markers of antioxidant status (SOD slutathione peroxidase, [GPx], and total anti-oxidant status [TAS]) was 33% (false-positive rate of 4.5%). Conclusion: Antioxidant supplementation was associated with better maternal and perinatal outcome in pregnant women with low antioxidant status than control supplementation with iron and folate alone. In a selected population already screened positive for low SOD, preeclampsia can be detected in 33% of asymptomatic cases in the first trimester using SOD, GPx, and TAS. It seems feasible that panels of both biochemical and molecular markers may be clinically useful in the prediction of this disease.     

The effect of calcium supplementation during pregnancy on fetal and infant growth: a nested randomized controlled trial within WHO calcium supplementation trial

Objective. To evaluate whether prenatal calcium supplementation affects fetal and infant growth during the first year of life.

Methods. Ninety-one pregnant women and 159 mothers and their infants enrolled beginning before 20 weeks gestation, and women received daily supplements containing either 1.5 g calcium or placebo. Women were examined by ultrasound at 20, 24, 28, 32 and 36 weeks to evaluate fetal biometry. During the first year after delivery, sub-groups of infants born from mothers participating in the trial were examined to assess infant growth. Anthropometric measurements of the infants were assessed. Mothers were enquired about lactation patterns, morbidities of the infants, separation from the mother, and admission to hospital.

Results. Ultrasound measurements of fetal biometry did not show any differences between fetuses whose mothers received calcium supplementation during pregnancy and those who received placebo. Concerning infant growth, the mean weight and head circumference of infants born to calcium-supplemented mothers were similar to those born to placebo-supplemented mothers during the first year of life. The mean mid-arm circumference and mean length were significantly higher in the infants of the calcium group at sixth and ninth month, respectively. But, at 12 months, there were no significant differences in any of the anthropometric measurements.

Conclusion. Calcium supplementation during pregnancy of women with low calcium intake does not have a noticeable impact on fetal and infant growth during the first year of life.     

Supplementation of folic acid in pregnancy and the risk of preeclampsia and gestational hypertension: a meta-analysis

Objectives

We aimed to systematically assess the relationship between folic acid supplementation in pregnancy and risk of preeclampsia and gestational hypertension.

Methods

The relevant studies were included by retrieving the Embase, PubMed and Cochrane library databases. Data extraction was conducted by two investigators independently. The risk ratio (RR) and 95% confidence interval (CI) were used as effect indexes to evaluate the relationship between folic acid supplementation and risk of gestational hypertension or preeclampsia. A subgroup analysis was performed according to the supplementation patterns of folic acid. The homogeneity of the effect size was tested across the studies, and publication biases were examined.

Results

In total, 13 cohort studies and 1 randomized controlled trial study was included, containing 160,562 and 149,320 women with and without folic acid supplementation during pregnancy. Pooled results showed that risk of gestational hypertension was not associated with the supplementation of folic acid. However, folic acid supplementation during pregnancy could significantly reduce the risk of preeclampsia. Moreover, the results of subgroup analysis showed that the decreased preeclampsia risk was associated with supplementation of multivitamins containing folic acid rather than folic acid alone.

Conclusions

Our findings indicate that the supplementation of multivitamins containing folic acid during pregnancy could significantly lower preeclampsia risk.

     

Calcium level during the first trimester of pregnancy as a predictor of preeclampsia

Objective: To examine the association between calcium levels during the first trimester of pregnancy and preeclampsia. Methods: The study population included registered births (n?=?5233) in a tertiary medical center between 2001 and 2011. A comparison was performed between women with and without hypocalcemia during the first trimester of pregnancy. A second analysis was performed after correcting calcium levels for albumin. Multiple logistic regression models were used to control for confounders. Receiver operating characteristic curve analysis graphs were used to describe the relationship between the true-positive rate (sensitivity) and the false-positive rate for different values of calcium during the first half of pregnancy in the prediction of preeclampsia. Results: Of 5233 deliveries, 841 (16%) had hypocalcemia and 4392 (84%) had a normal calcium level. No significant difference were found between the groups regarding mild preeclampsia [odds ratio (OR) = 1.216; 95% confidence interval (CI) 0.831–1.779; p?=?0.312], severe preeclampsia (OR?=?1.618; 95% CI 0.919–2.849; p?=?0.092) and any hypertensive disorders (OR?=?1.324; 95% CI 0.963–1.821; p?=?0.083). Conclusions: Hypocalcemia during the first trimester of pregnancy is not a risk factor for preeclampsia.     

Progesterone supplementation for preventing preterm birth: a systematic review and meta-analysis

AIM: The aim of this study is to assess the role of progesterone in preterm birth prevention. METHODS: A MEDLINE search (from 1966 to the present; date of last search January 2005) was performed - using the key words progesterone, pregnancy, preterm birth, preterm labor, and randomized, controlled trial - in order to identify randomized, controlled trials in which progesterone (either intramuscular or vaginal administration) was compared with placebo or no treatment. Data were extracted and a meta-analysis was performed. RESULTS: Seven randomized, controlled trials were identified. Women who received progesterone were statistically significantly less likely to give birth before 37 weeks (seven studies, 1020 women, RR = 0.58, 95% CI = 0.48-0.70), to have an infant with birth weight of < or =2.5 kg (six studies, 872 infants, RR = 0.62, 95% CI = 0.49-0.78), or to have an infant diagnosed with intraventricular hemorrhage (one study, 458 infants, RR = 0.25, 95% CI = 0.08-0.82). CONCLUSIONS: For progesterone supplementation to be advocated for women at the risk of preterm birth, the prolongation of gestation demonstrated in this meta-analysis must translate into improved infant outcomes, including a reduction in mortality. There is currently insufficient information to allow recommendations regarding the optimal dose, route, and timing of administration of progesterone supplementation.     

A Randomised,Double-Blinded,Placebo-Controlled Study of the Phosphodiesterase Type 5 Inhibitor Sildenafil for the Treatment of Preeclampsia

Objective:?To determine if the phosphodiesterase type 5 inhibitor sildenafil prolongs pregnancy in women with preeclampsia.?Methods:?Women with preeclampsia at gestational ages 24–34 weeks were recruited from nine hospitals in the UK, and randomly assigned to sildenafil citrate or placebo. Medication was increased every 3 days from 20 mg three times daily (tid), to 40 mg, and 80 mg tid. The primary endpoint was prolongation of pregnancy from randomisation to delivery (days). Secondary endpoints were markers of maternal disease and cord pH at delivery and infant weight. Details of all adverse events were also collected. Plasma samples were taken to establish pharmacokinetic information. Data analysed on a modified intention to treat analysis. The study had a power of >95% to detect a difference of 5 days.?Results:?Of 35 women, 17 were allocated to sildenafil and 18 to placebo. There was no difference in time from randomisation to delivery in the two treatment groups, with a median time of 4 days (range 1–15) in the sildenafil group and 4.5 days (range 1–30) in the placebo group. Sildenafil achieved maximum drug concentrations of 48 ng/ml, 88 ng/ml, and 271 ng/ml after 3 days of 20 mg, 40 mg and 80 mg tid, respectively.?Conclusion:?We have safely conducted a clinical trial of a drug not routinely used during pregnancy. Sildenafil in the escalating dose regimen 20–80 mg tid was well tolerated, with no increase in maternal or fetal morbidity or mortality but did not prolong pregnancy duration in women with preeclampsia. (ClinicalTrials.gov number, NCT 00141310).     

World Health Organisation multicentre randomised trial of supplementation with vitamins C and E among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries

Objective  To determine if vitamin C and E supplementation in high-risk pregnant women with low nutritional status reduces pre-eclampsia.
Design  Multicentred, randomised, controlled, double-blinded trial.
Setting  Antenatal care clinics and Hospitals in four countries.
Population  Pregnant women between 14 and 22 weeks' gestation.
Method  Randomised women received 1000 mg vitamin C and 400 iu of vitamin E or placebo daily until delivery.
Main outcome measures  Pre-eclampsia, low birthweight, small for gestational age and perinatal death.
Results  Six hundred and eighty-seven women were randomised to the vitamin group and 678 to the placebo group. Groups had similar gestational ages (18.1; SD 2.4 weeks), socio-economic, clinical and demographical characteristics and blood pressure at trial entry. Risk factors for eligibility were similar, except for multiple pregnancies: placebo group (14.7%), vitamins group (11.8%). Previous pre-eclampsia, or its complications, was the most common risk factor at entry (vitamins 41.6%, placebo 41.3%). Treatment compliance was 87% in the two groups and loss to follow-up was low (vitamins 2.0%, placebo 1.3%). Supplementation was not associated with a reduction of pre-eclampsia (RR: 1.0; 95% CI: 0.9–1.3), eclampsia (RR: 1.5; 95% CI: 0.3–8.9), gestational hypertension (RR: 1.2; 95% CI: 0.9–1.7), nor any other maternal outcome. Low birthweight (RR: 0.9; 95% CI: 0.8–1.1), small for gestational age (RR: 0.9; 95% CI: 0.8–1.1) and perinatal deaths (RR: 0.8; 95% CI: 0.6–1.2) were also unaffected.
Conclusion  Vitamins C and E at the doses used did not prevent pre-eclampsia in these high-risk women.     

Racial and ethnic disparities in universal cervical length screening with transvaginal ultrasound

Objective: Determine if race or ethnicity is associated with missed or late transvaginal cervical length screening in a universal screening program.

Methods: Retrospective cohort study of nulliparous women with singleton gestations and a fetal anatomical ultrasound from 16–24 weeks’ gestation from January 2012 to November 2013. We classified women into mutually exclusive racial and ethnic groups: non-Hispanic black (black), Hispanic, Asian, non-Hispanic white (white), and other or unknown race. We used log-binomial regression to calculate the risk ratio (RR) and 95% confidence interval (CI) of missed or late (≥20 weeks’ gestation) screening versus optimally timed screening between the different racial and ethnic groups.

Results: Among the 2967 women in our study population, 971 (32.7%) had either missed or late cervical length screening. Compared to white women, black (RR: 1.3; 95% CI: 1.1–1.5) and Hispanic (RR:1.2; 95% CI: 1.01–1.5) women were more likely to have missed or late screening. Among women screened, black (versus white) women were more likely to be screened late (RR: 2.2; 95% CI: 1.6–3.1).

Conclusions: Black and Hispanic women may be more likely to have missed or late cervical length screenings.