Progesterone supplementation for prevention of preterm labor: A randomized controlled trial

ObjectiveTo evaluate the efficacy of intramuscular progesterone in prevention of preterm labor in high risk cases.DesignRandomized controlled trial.SettingAin Shams Maternity hospital.Materials and methodsSingleton pregnant women in their second trimester with a history of previous preterm labor were divided into two groups: progesterone group: received 17-α-hydroxy progesterone caproate (Cidolut depot) one dose of 250mg IM once weekly until 36weeks and placebo group: received standard dose of placebo IM per week. Follow up till delivery.ResultsThe mean gestational age was 37.4±1.5 in progesterone group vs. 34.7±2.4 in placebo group (P<0.05). In the progesterone group 8 of 25 women delivered before completion of 37 weeks of gestation (32%) and 17 women delivered full term (68%). In placebo group, 13 of 25 women delivered before completion of 37weeks of gestation (52%) and 12 women delivered full term (48%).ConclusionOur findings support 17-α-hydroxy progesterone as a successful drug in the prevention and decreasing the rate of recurrent preterm labor.     

Calcium supplementation reduces the risk of pregnancy-induced hypertension in an Andes population

Summary. Previous studies have suggested that increased dietary calcium is associated with a decreased occurrence of pregnancy-induced hypertension. In this study 106 young healthy nulliparous women, residing in Quito, Ecuador, were enrolled in a double-blind, randomized, controlled clinical trial. From 24 weeks gestation until delivery they received either 2 g of elemental calcium per day or a placebo. Calcium supplementation was associated with a significantly decreased risk of pregnancy-induced hypertension, with 4.1% developing pregnancy-induced hypertension in the treatment group versus 27.9% in the placebo group. Treatment was associated with a decrease in both systolic and diastolic blood pressure over the course of pregnancy. In addition, there was a small but significant increase in serum ionized calcium levels in the calcium-supplemented group during the treatment period.     

Calcium supplementation reduces the risk of pregnancy-induced hypertension in an Andes population

Previous studies have suggested that increased dietary calcium is associated with a decreased occurrence of pregnancy-induced hypertension. In this study 106 young healthy nulliparous women, residing in Quito, Ecuador, were enrolled in a double-blind, randomized, controlled clinical trial. From 24 weeks gestation until delivery they received either 2 g of elemental calcium per day or a placebo. Calcium supplementation was associated with a significantly decreased risk of pregnancy-induced hypertension, with 4.1% developing pregnancy-induced hypertension in the treatment group versus 27.9% in the placebo group. Treatment was associated with a decrease in both systolic and diastolic blood pressure over the course of pregnancy. In addition, there was a small but significant increase in serum ionized calcium levels in the calcium-supplemented group during the treatment period.     

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.     

Progesterone supplementation and the prevention of preterm birth

Preterm birth is currently the most important problem in maternal-child health in the United States and possibly throughout the world. It complicates one in eight US deliveries, and accounts for over 85% of all perinatal morbidity and mortality. Although survival of preterm infants has increased steadily over the past four decades-due in large part to the use of antenatal corticosteroids, improvements in neonatal resuscitation, and the introduction of neonatal intensive care units-efforts to prevent preterm birth have been largely unsuccessful. On February 3, 2011, the US Food and Drug Administration (FDA) approved the use of progesterone supplementation (hydroxyprogesterone caproate) during pregnancy to reduce the risk of recurrent preterm birth in women with a history of at least one prior spontaneous preterm delivery. This is the first time that the FDA has approved a medication for the prevention of preterm birth, and represents the first approval of a drug specifically for use in pregnancy in almost 15 years. This article reviews the evidence behind the use of progesterone for the prevention of preterm birth, and provides guidelines for the use of progesterone supplementation in clinical practice. A number of areas of ongoing controversy are addressed, including the optimal formulation and route of administration, the safety of progesterone supplementation in pregnancy, and its proposed mode of action.     

A randomized trial of micronized progesterone for the prevention of recurrent preterm birth

We sought to evaluate the effectiveness of daily oral micronized progesterone (MP) in preventing recurrent spontaneous preterm birth (RSPB) and whether MP increases maternal serum progesterone. We performed a pilot, single-center, randomized, double-blind, placebo-controlled trial in women with a prior preterm birth and current singleton gestation at 16 to 20 weeks ( N = 33). The primary outcome was the rate of RSPB. Subjects were given either daily MP (400 mg) or placebo from 16 to 34 weeks. Serum progesterone was obtained at enrollment and in the late second/early third trimester. Pregnancy outcome data were collected. RSPB occurred in 5/19 (26.3%) in the MP group versus 8/14 (57.1%) in placebo group ( P = 0.15). The mean age at delivery was 37.0 ± 2.7 weeks for the MP group versus 35.9 ± 2.6 weeks for the placebo ( P = 0.3). Mean serum progesterone at 28 weeks was 122.6 ± 61.8 pg/mL for MP group versus 90.1 ± 38.7 pg/mL for placebo ( P = 0.19). MP was associated with a trend toward a reduction in RSPB and an increase in the maternal serum progesterone. Although the primary outcome in this pilot study did not reach statistical significance, the results suggest a favorable trend meriting further investigation.     

Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial

Background

Adequate vitamin D concentrations during pregnancy are necessary to neonatal calcium homeostasis, bone maturation and mineralization. The aim of study is to evaluate serum vitamin D concentrations in mothers and their newborns and effect of vitamin D deficiency on pregnancy outcomes.

Methods

552 pregnant women were recruited from Tehran University educating hospitals in the winter of 2002. Maternal and cord blood samples were taken at delivery. The serum was assayed for 25-hydroxyvitamin D3, calcium, phosphorus and parathyroid hormone.

Results

The prevalence of vitamin D deficiency in maternal and cord blood samples were 66.8% and 93.3%, respectively (<35 nmol/l). There was significant correlation between maternal and cord blood serum concentrations of vitamin D. In mothers with vitamin D deficiency, cord blood vitamin D concentrations was lower than those from normal mothers (P = .001). Also, a significant direct correlation was seen between maternal vitamin D intake and weight gain during pregnancy.

Conclusion

Consideration to adequate calcium and vitamin D intake during pregnancy is essential. Furthermore, we think it is necessary to reconsider the recommendation for vitamin D supplementation for women during pregnancy.     

Cerclage for prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination: a randomized trial

OBJECTIVE: The purpose of this study was to determine the efficacy of cerclage and bed rest versus bed rest-only for the prevention of preterm birth in women with a short cervix found on transvaginal ultrasound examination. STUDY DESIGN: Women with > or =1 of high-risk factors for preterm birth (> or =1 preterm birth at < 35 weeks of gestation, > or =2 curettages, diethylstilbestrol exposure, cone biopsy, Mullerian anomaly, or twin gestation) were screened with transvaginal ultrasonography of the cervix every 2 weeks from 14 weeks of gestation to 23 weeks 6 days of gestation. Enrollment was offered to both asymptomatic women who were at high risk and who were identified to have short cervix (< 25 mm) or significant funneling (>25%) and nonscreened women who were at low risk and who were identified incidentally. The women who gave written consent were assigned randomly to receive either McDonald cerclage or bed rest-only. Both groups received similar counseling and treatment. Primary outcome was preterm birth at < 35 weeks of gestation. RESULTS: Sixty-one women were assigned randomly. Forty-seven pregnancies (77%) were high-risk singleton gestations. Thirty-one women (51%) were allocated to cerclage, and 30 women (49%) were allocated to bed rest. There were no differences between the groups in demographic characteristics, risk factors, and cervical variables. Preterm birth at < 35 weeks of gestation occurred in 14 women (45%) in the cerclage group and in 14 women (47%) in the bed rest group (relative risk, 0.94; 95% CI, 0.34-2.58). There was no difference in any obstetric or neonatal outcomes. A subanalysis of singleton pregnancies with previous preterm birth at < 35 weeks of gestation and a short cervix of < 25 mm (n = 31 women) also revealed no significant difference in recurrent preterm birth at < 35 weeks of gestation (40% vs 56%; relative risk, 0.52; 95% CI, 0.12-2.17). CONCLUSION: Cerclage did not prevent preterm birth in women with a short cervix. These results should be confirmed by larger trials.     

A randomized controlled trial of acupuncture for initiation of labor in nulliparous women.

OBJECTIVE: To evaluate the utility of outpatient acupuncture for labor stimulation. METHODS: Nulliparous women at 39 4/7 weeks or greater with a singleton gestation and Bishop score of less than 7 were randomized to usual medical care (control group) versus usual care and three outpatient acupuncture treatments (acupuncture group). Each treatment consisted of eight needles applied to bilateral points LI4, SP6, UB31, and UB32. The primary outcome was time elapsed from the time of randomization to delivery. Secondary outcomes included rates of cesarean section and induction of labor. Medical records were abstracted for maternal demographic, medical, and delivery outcome data. A priori sample size calculation revealed that 56 women were required to detect a 72-hour difference in delivery time with a power of 83% and an alpha of 0.05. Student's t-test, Chi-square, and Kaplan-Meier statistics were used to compare groups. RESULTS: Fifty-six women were randomized and completed the study procedures. Race, age, gestational age, and cervical Bishop score were similar in both groups. Mean time to delivery occurred 21 hours sooner in the acupuncture group, but this difference did not reach statistical significance (p = 0.36). Compared to controls, women in the acupuncture group tended to be more likely to labor spontaneously (70% vs. 50%, p = 0.12) and less likely to deliver by cesarean section (39% vs. 17%, p = 0.07). Of women who were not induced, those in the acupuncture group were more likely to be delivered than the controls at any point after enrollment (p = 0.05). CONCLUSION: Acupuncture is well tolerated among term nulliparous women and holds promise in reducing interventions that occur in post-term pregnancies.     

A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study

OBJECTIVE: To determine whether metronidazole reduces early preterm labour in asymptomatic women with positive vaginal fetal fibronectin (fFN) in the second trimester of pregnancy. DESIGN: Randomised placebo-controlled trial. SETTING: Fourteen UK hospitals (three teaching). POPULATION: Pregnancies with at least one previous risk factor, including mid-trimester loss or preterm delivery, uterine abnormality, cervical surgery or cerclage. METHODS: Nine hundred pregnancies were screened for fFN at 24 and 27 weeks of gestation. Positive cases were randomised to a week's course of oral metronidazole or placebo. MAIN OUTCOME MEASURES: Primary outcome was delivery before 30 weeks of gestation. Secondary outcomes included delivery before 37 weeks. RESULTS: The Trial Steering Committee (TSC) recommended the study be stopped early; 21% of women receiving metronidazole (11/53) delivered before 30 weeks compared with 11% (5/46) taking placebo [risk ratio 1.9, 95% confidence interval (CI) 0.72-5.09, P = 0.18]. There were significantly more preterm deliveries (before 37 weeks) in women treated with metronidazole 33/53 (62%) versus placebo 18/46 (39%), risk ratio 1.6, 95% CI 1.05-2.4. fFN was a good predictor of early preterm birth in these asymptomatic women; positive and negative predictive values (24 weeks of gestation) for delivery by 30 weeks were 26% and 99%, respectively (positive and negative likelihood ratios 15, 0.35). CONCLUSION: Metronidazole does not reduce early preterm birth in high risk pregnant women selected by history and a positive vaginal fFN test. Preterm delivery may be increased by metronidazole therapy.     

Cervical cerclage for prevention of preterm birth in women with twin pregnancy.

OBJECTIVE: To compare the effect of elective cervical cerclage in women with twin pregnancy on gestational age at time of delivery. METHOD: In a pragmatic fashion women in Abha Maternity Hospital, Saudi Arabia with twin gestations were allocated to receive either an elective cerclage (group I) or no cerclage (group II). Elective cerclage was performed at 12 to 14 weeks of gestation after sonographic examination of the fetus to confirm gestational age and exclude major congenital anomalies. In all cases, follow up of the pregnancy was continued until delivery. RESULTS: Of the 176 twin pregnancies included, cerclage was performed in 76 women, and no cerclage in 100 women. In Group I: 12 pregnancies ended in spontaneous miscarriage, 37 in preterm labor, and 27 women reached full term. There were a total of 106 live births in 62 women. In Group II: 8 women aborted, 44 women ended in preterm labor and 48 women reached full term. There were a total of 160 live births in 89 women. The gestational age at delivery ranged from 20 to 41 weeks. Multiple regression analysis did not show association between cerclage and time of delivery, although a trend was observed (P=0.056). CONCLUSION: Elective cerclage contributes little in prolongation of gestational age at the time of delivery in women with twin pregnancy, especially in women of high parity. Those with a previous history of preterm labor may be a subgroup that could benefit from elective cerclage.     

A randomized controlled trial of acupuncture for initiation of labor in nulliparous women

Objective. To evaluate the utility of outpatient acupuncture for labor stimulation.

Methods. Nulliparous women at 39 4/7 weeks or greater with a singleton gestation and Bishop score of less than 7 were randomized to usual medical care (control group) versus usual care and three outpatient acupuncture treatments (acupuncture group). Each treatment consisted of eight needles applied to bilateral points LI4, SP6, UB31, and UB32. The primary outcome was time elapsed from the time of randomization to delivery. Secondary outcomes included rates of cesarean section and induction of labor. Medical records were abstracted for maternal demographic, medical, and delivery outcome data. A priori sample size calculation revealed that 56 women were required to detect a 72-hour difference in delivery time with a power of 83% and an alpha of 0.05. Student's t-test, Chi-square, and Kaplan–Meier statistics were used to compare groups.

Results. Fifty-six women were randomized and completed the study procedures. Race, age, gestational age, and cervical Bishop score were similar in both groups. Mean time to delivery occurred 21 hours sooner in the acupuncture group, but this difference did not reach statistical significance (p = 0.36). Compared to controls, women in the acupuncture group tended to be more likely to labor spontaneously (70% vs. 50%, p = 0.12) and less likely to deliver by cesarean section (39% vs. 17%, p = 0.07). Of women who were not induced, those in the acupuncture group were more likely to be delivered than the controls at any point after enrollment (p = 0.05).

Conclusion. Acupuncture is well tolerated among term nulliparous women and holds promise in reducing interventions that occur in post-term pregnancies.     

孕激素在预防早产中的作用

早产的发生率仍持续不降,甚至逐年攀升,早产及由此出生的早产儿是导致围产儿死亡及致残的重要原因,究其原因是早产的预防及治疗效果不佳。早产的预防和治疗中强调以综合方案为主,近年来孕激素在早产的预防和治疗中的应用取得了一定的效果,但也存在较大的争议,文章就国内外相关的临床研究、专家共识等文献资料进行回顾,希望对临床有所裨益。     

Effect of L-arginine on blood pressure in pregnancy-induced hypertension: a randomized placebo-controlled trial.

OBJECTIVE: To evaluate the antihypertensive efficacy of L-arginine (L-Arg) repeated infusions in women affected by gestational hypertension. METHODS: The women were referred to obstetric units in order to assess their clinical conditions and to exclude the presence of severe fetal and/or maternal complications. Inclusion criteria were: maternal age range 16-45 years, diagnosis of gestational hypertension without proteinuria (patients normotensive until the 20th week), and gestational age ranging between 24 and 36 weeks. Each woman was allocated to receive either L-arginine (20 g/500 mL) or placebo treatment through an i.v. line. The infusion was carried out in the morning from 8 a.m. to 10 a.m. and it was repeated for the next four consecutive days. Systolic and diastolic blood pressure values as well as heart rate were recorded with the patient in an upright, seated position at 08:00, 12:00, 16:00 and 20:00 h. RESULTS: Maternal clinical features such as age, height, weight, and gestational age at inclusion were similar between groups. Both systolic and diastolic blood pressures were reduced by treatment, the effect of L-arginine being significantly higher than that of the placebo (systolic values F = 8.59, p < 0.005; diastolic values F = 3.36; p < 0.001). Twenty women assigned to the L-Arg group (32.2%) and 23 to the placebo group (37.7%) were concomitantly treated with antihypertensives before starting the study. Analyzing the subgroup of patients not receiving antihypertensive drugs we found that L-arginine was superior to placebo in lowering systolic (F = 5.42, p < 0.005) and diastolic (F = 2.20, p < 0.005) blood pressure values. CONCLUSIONS: In conclusion, these data support the use of L-Arg as an antihypertensive agent for gestational hypertension especially in view of the other beneficial effects nitric oxide donors display in pregnancy. Further, L-Arg seems well tolerated since in this sample none of the patients reported adverse effects requiring study interruption.