Vitamin C supplementation to prevent premature rupture of the chorioamniotic membranes: a randomized trial

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Esther Casanueva, Carmina Ripoll, Maricruz Tolentino, Rosa Maria Morales, Frania Pfeffer, Pablo Vilchis and Felipe Vadillo-Ortega

1 From the Public Health Research Branch (EC, CR, MT, RMM, and FP), the Department of Obstetrics and Gynecology (PV), and the Direction of Research (FV-O), National Institute of Perinatology, Mexico City, Mexico.

Background: Vitamin C is involved in the synthesis and degradation of collagen and is important for maintenance of the chorioamniotic membranes. Inadequate availability of ascorbic acid during pregnancy has been proposed as a risk factor for premature rupture of the chorioamniotic membranes (PROM).

Objective: The objective of the study was to evaluate the effectiveness of 100 mg vitamin C/d in preventing PROM.

Design: A controlled double-blind trial was performed. Pregnant women (n = 126) in their 20th wk of gestation were invited; 120 accepted and were randomly assigned to 2 groups (100 mg vitamin C/d or placebo). Every 4 wk, plasma and leukocyte vitamin C concentrations were measured, and each subject was evaluated for cervicovaginal infection. The incidence of PROM was recorded for each group as an indicator of the protective effect of vitamin C supplementation.

Results: One hundred nine patients finished the study. Mean plasma vitamin C concentrations decreased significantly throughout the pregnancy in both groups (P = 0.001), and there were no significant differences between groups. Between weeks 20 and 36, mean leukocyte vitamin C concentrations decreased from 17.5 to 15.23 µg/108 cells in the placebo group and increased from 17.26 to 22.17 µg/108 cells in the supplemented group (within- and between-group differences: P = 0.001). The incidence of PROM was 14 per 57 pregnancies (24.5%) in the placebo group and 4 per 52 pregnancies (7.69%) in the supplemented group (relative risk: 0.26; 95% CI: 0.078, 0.837).

Conclusion: Daily supplementation with 100 mg vitamin C after 20 wk of gestation effectively lessens the incidence of PROM.

Vitamins C and E in the latency period in women with preterm premature rupture of membranes

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S. Bornaa, Corresponding Author Contact Information, H. Bornab and B. Daneshbodie
aDepartment of Perinatology, Tehran University of Medical Sciences, Tehran, Iran
bDepartment of Pediatrics, Shahed University of Medical Sciences, Tehran, Iran
Received 1 December 2004; accepted 23 March 2005. Available online 23 May 2005.

Abstract

Objective: To determine whether supplementation with vitamins C and E after preterm premature rupture of membranes (PPROM) is associated with an increased latency period. Methods: In this double-blind, randomized, controlled trial, 60 women with singleton pregnancies of 26 to 34 weeks' duration and PPROM were randomly assigned to vitamin C (500 mg/day) and vitamin E (400 IU/day) or placebo until delivery. All women received 2 doses of betamethasone in the first 24 h after admission as well as broad-spectrum antibiotic prophylaxis.

Results: Important demographic, as well as clinical characteristics such as number of cases of chorioamnionitis, early neonatal sepsis, and respiratory distress syndrome, were similar in the 2 groups. A statically significant difference in the mean ± S.D. number of days of latency was found between the groups (10.5 ± 5.2 days vs. 3.5 ± 4.0 days (P = 0.03).

Conclusion: Vitamins C and E supplementation of after PPROM is associated with a longer latency before delivery.

Prevention of recurrent preterm delivery by 17 Alpha-Hydroxyprogesterone Caproate

Learn more about 17p shots here: http://www.hydroxyprogesterone.com/

New England Journal of Medicine Abstract

Volume 348:2379-2385
June 12, 2003
Number 24

Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesterone Caproate

Paul J. Meis, M.D., Mark Klebanoff, M.D., Elizabeth Thom, Ph.D., Mitchell P. Dombrowski, M.D., Baha Sibai, M.D., Atef H. Moawad, M.D., Catherine Y. Spong, M.D., John C. Hauth, M.D., Menachem Miodovnik, M.D., Michael W. Varner, M.D., Kenneth J. Leveno, M.D., Steve N. Caritis, M.D., Jay D. Iams, M.D., Ronald J. Wapner, M.D., Deborah Conway, M.D., Mary J. O'Sullivan, M.D., Marshall Carpenter, M.D., Brian Mercer, M.D., Susan M. Ramin, M.D., John M. Thorp, M.D., Alan M. Peaceman, M.D., for the National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network

Background:
Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery.

Methods:
We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle.

Results:
Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation (incidence, 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group; relative risk, 0.66 [95 percent confidence interval, 0.54 to 0.81]), delivery at less than 35 weeks of gestation (incidence, 20.6 percent vs. 30.7 percent; relative risk, 0.67 [95 percent confidence interval, 0.48 to 0.93]), and delivery at less than 32 weeks of gestation (11.4 percent vs. 19.6 percent; relative risk, 0.58 [95 percent confidence interval, 0.37 to 0.91]). Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen.

Conclusions:
Weekly injections of 17P resulted in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants.

Preterm delivery — that is, delivery before 37 completed weeks of gestation — is the major determinant of infant mortality in developed countries.1 Preterm delivery is more common in the United States than in many other developed countries and is the factor most responsible for the relatively high infant mortality in this country.1 The rate of preterm delivery in the United States has increased progressively from 9 percent to 12 percent over the past two decades.2 Despite many trials of reduced activity, tocolytic therapy, antibiotic therapy, and other strategies for prevention, no effective and reproducible method of preventing preterm delivery has been demonstrated.3

One treatment that showed promise in small trials was prophylactic treatment with progestational compounds.4,5,6,7 Not all trials reported positive results.8,9 One meta-analysis found no evidence of effectiveness of progestational compounds in the prevention of preterm delivery or the prevention of recurrent miscarriage.10 Another meta-analysis, restricted to trials of 17 alpha-hydroxyprogesterone caproate (17P), a natural metabolite of progesterone, showed, in composite, a significant reduction in the rate of preterm delivery.11 We therefore chose this pharmacologic agent as the active drug for our study.

Women who have had a preterm delivery are at especially high risk for preterm delivery in a subsequent pregnancy.12 We therefore conducted a multicenter trial to test the effectiveness of 17P as compared with placebo in the prevention of recurrent preterm delivery in this group of women.

Causes of preterm birth

Some causes of preterm birth

Although the cause is often unknown, a variety of factors play a role in preterm birth:

• Certain genital tract infections, such as chlamydia, bacterial vaginosis (BV), and trichomoniasis, are associated with preterm delivery.

Substances produced by bacteria can weaken the membranes around the amniotic sac and cause it to rupture early. Even when the membranes remain intact, bacteria can cause preterm labor if they get into the amniotic fluid or sac.

You may have been checked for chlamydia and gonorrhea at your first prenatal visit, and you would have been treated immediately if you'd tested positive for either of these sexually transmitted infections.

If you've had a previous preterm birth, you may also have been screened for bacterial vaginosis. Although some studies show that treating BV in the second and third trimesters reduces the risk of preterm labor in women with a history of preterm birth, other research has found that it makes no difference. So experts don't agree on whether it's worthwhile to test pregnant women who don't have symptoms. (If you have symptoms of bacterial vaginosis, you'll be tested and treated with antibiotics, if needed.)

You probably won't be tested for trichomoniasis unless you have symptoms. Some research suggests that treating women for trichomoniasis during pregnancy actually increases the risk of preterm birth.

• Having a problem with the placenta, such as placenta previa or placental abruption.

• Having structural abnormalities of the uterus or cervix, such as a cervix that's shorter than 25 millimeters and that effaces or dilates without contractions (cervical insufficiency).

• Having an excessively large uterus, which is often the case when you're pregnant with multiples or have too much amniotic fluid.

• Certain chronic maternal illnesses may be related to preterm labor, such as diabetes, sickle cell anemia, severe asthma, lupus, inflammatory bowel disease, and chronic active hepatitis. Other conditions to watch for include non-uterine infections, such as a kidney infection or pneumonia; abdominal surgery, such as having your appendix taken out; trauma to the abdomen; and periodontitis (a gum infection that goes into the bone and other tissues that support your teeth).

Preeclampsia

Preeclampsia is a disorder that occurs only during pregnancy and the postpartum period and affects both the mother and the unborn baby. Affecting at least 5-8% of all pregnancies, it is a rapidly progressive condition characterized by high blood pressure and the presence of protein in the urine. Swelling, sudden weight gain, headaches and changes in vision are important symptoms; however, some women with rapidly advancing disease report few symptoms.

Typically, preeclampsia occurs after 20 weeks gestation (in the late 2nd or 3rd trimesters or middle to late pregnancy), though it can occur earlier. Proper prenatal care is essential to diagnose and manage preeclampsia. Preeclampsia, Pregnancy Induced Hypertension (PIH) and toxemia are closely related conditions. HELLP Syndrome and eclampsia are other manifestations of the same syndrome. It is important to note that research shows that more women die from preeclampsia than eclampsia and one is not necessarily more serious than the other.

Preeclampsia and other hypertensive disorders of pregnancy are a leading global cause of maternal and infant illness and death. By conservative estimates, these disorders are responsible for 76,000 deaths each year.