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Biomedical subjects

R L Goldenberg

Publications and source records attributed to R L Goldenberg.

At least 19 recordsLinked to original sources

Stillbirth in developing countries.

OBJECTIVE: To conduct a systematic review of the literature on stillbirths in developing countries. METHOD: Review of the English literature for all articles related to stillbirth in developing countries published from 1975 to 2005. RESULTS: Because almost half of the deliveries in developing countries occur at home, under-reporting of stillbirths is a huge problem, and reliable data about rates and causes are difficult to obtain. Hospital stillbirth data are often subject to substantial bias and the ability to generalize from these data is unknown. Nevertheless, at least 4 million stillbirths occur yearly, the vast majority in developing countries, with rates in many developing countries ten-fold higher than elsewhere. Prolonged and obstructed labor, preeclampsia and various infections, all without adequate treatment, account for the majority of stillbirths. CONCLUSION: Despite the large number of stillbirths worldwide, the topic of stillbirths in developing countries has received very little research, programmatic or policy attention. Better access to appropriate obstetric care, especially during labor, should reduce developing country stillbirth rates dramatically.

Developing Countries↗

Stillbirth: a review.

Stillbirth occurs in nearly 1% of all births in the USA, and is one of the most common but least studied adverse pregnancy outcomes. The many risk factors for and causes of stillbirth are presented. Over the past several decades, the rate of stillbirth has been substantially reduced, with the reduction most apparent in those stillbirths previously occurring at term and/or in labor. Reductions have occurred because of reductions in risk factors (i.e. prevention of Rh disease and better control of diabetes), better antepartum monitoring of those with risk factors followed by early delivery for those fetuses found to be at risk (i.e. growth restriction, maternal pre-eclampsia), better intrapartum fetal monitoring, increases in Cesarean section for those at risk, and early detection of congenital anomalies followed by termination prior to the time that these early fetal deaths are classified as stillbirths. Finally, the value of using fetal autopsy and placental examination to determine the cause of death accurately, both for research purposes and for patient counseling in future pregnancies, is explored.

Female↗

Birthweight-specific neonatal mortality in developing countries and obstetric practices.

OBJECTIVES: To evaluate birthweight-specific neonatal mortality and perinatal interventions in major medical centers in developed and developing countries. METHODS: A survey was developed and electronically mailed to 13 medical centers participating in the Global Network for Perinatal and Reproductive Health (GNPRH). The ability of a center to provide requested data was assessed. The mortality rates and use of specific perinatal interventions in centers in developing countries were compared with developed countries. RESULTS: Nine centers in developing countries responded to the survey, and three centers in developed countries were used for comparison. Data collection was highly variable. Most developing country centers were able to provide data by birthweight but not by gestational age. The differences in mortality rates between developing and developed countries were more pronounced at lower gestational ages and birthweights. A difference was found in perinatal interventions between developing and developed countries. In the former, viability was generally considered 28 weeks, and the gestational age at which cesarean sections were usually performed for the sake of the fetus at preterm gestations varied from 26 to 37 weeks. Most centers did not routinely induce for pPROM; only five out of nine centers used antibiotics to prolong latency. Most centers used tocolysis beginning at 26-28 weeks through 32-37 weeks, and a variety of tocolytic agents were used. Most centers routinely used corticosteroids for preterm infants, and all centers employed repeat weekly steroid dosing if undelivered. CONCLUSIONS: Despite the fact that the GNPRH centers included in this study represent some of the best health care available in these countries, they lag far behind centers in developed countries in neonatal mortality rates and their use of various obstetric practices. Furthermore, incomplete and inconsistent data collection complicates the evaluation of the factors contributing to high neonatal mortality rates.

Birth Weight↗

Elevated amniotic fluid ferritin levels are associated with inflammation-related pregnancy loss following mid-trimester amniocentesis.

OBJECTIVE: Occult infection accounts for up to 12% of pregnancy losses following genetic amniocentesis. Elevated serum and cervical fluid levels of ferritin, an acute-phase reactant, have been associated with spontaneous preterm delivery. We determined the association between amniotic fluid (AF) ferritin levels and post-amniocentesis pregnancy loss. METHODS: We performed a case-control study involving 66 women with a non-anomalous fetus who had a spontaneous pregnancy loss within 30 days following genetic amniocentesis and 66 term controls matched for maternal age, gestational age, time of test and indication for amniocentesis. Amniotic fluid ferritin and interleukin-6 (IL-6) levels were measured using commercially available kits. RESULTS: Mean (+/- SD) AF ferritin levels were similar between the cases (19.3 +/- 21.4 ng/ml) and the controls (19.8 +/- 22.7ng/ml) (p = 0.9). Mean (+/- SD) AF IL-6 levels were significantly higher in the women with post-amniocentesis pregnancy loss (4.0 +/- 13.1 ng/ml) than in controls (0.5 +/- 0.7 ng/ml) (p = 0.04). A significant proportion (12.1%, 8/66) of the women with post-amniocentesis pregnancy loss had elevated amniotic fluid IL-6 levels (> 3 SD, 2.5 ng/ml) indicating inflammation, as compared to none in the control group (p = 0.01). In this subgroup of women with pregnancy loss and elevated IL-6 levels, AF ferritin levels were significantly elevated (52.0 +/- 45.5 ng/ml) compared to the level in women who had a term delivery (19.8 +/- 22.7 ng/ml) (p = 0.002), and were strongly correlated with IL-6 levels among the cases (r = 0.67, p < 0.001). CONCLUSION: The strong correlation of AF ferritin with IL-6 levels, along with the high ferritin values in cases with high AF IL-6, indicates that ferritin is a marker of inflammation in asymptomatic women destined to have an early pregnancy loss.

Abortion, Spontaneous↗

Perinatal HIV transmission: developing country considerations.

In many developing countries, because the prevalence of maternal HIV infection is high (more than 30% in some sub-Saharan African countries) and the resources commonly used to prevent transmission in developed countries are generally not available, transmission of HIV from mother to infant is a devastating problem. Countries already experiencing infant mortality rates 10- to 20-fold greater than those in developed countries can expect a doubling of infant and childhood mortality due to HIV. Those infants who escape infection themselves can expect to be orphaned in early childhood. Low-cost antiviral therapy can reduce transmission substantially, but many countries do not have the infrastructure to screen pregnant women for HIV and appropriately treat the mothers and infants. In developing countries, reduction in maternal-child transmission is feasible, but will require substantial additional resources and a well-functioning obstetric care system.

Anti-HIV Agents↗

Zambian women's attitudes toward mass nevirapine therapy to prevent perinatal transmission of HIV.

Use of mass nevirapine therapy--universal provision of the drug without HIV testing--for prevention of perinatal HIV in high prevalence settings with extreme resource constraints is a controversial strategy. A quarter of pregnant Zambian women surveyed would prefer to receive nevirapine through a non-testing mass strategy, and most would support mass therapy as a policy if it would make the drug available to a larger proportion of the at-risk population.

Anti-HIV Agents↗

Prospects for research in reproductive health and birth outcomes.

In the last several decades there have been major improvements in the ability to control fertility, treat infertility, and reduce maternal, fetal, and infant mortality. However, neither the preterm birth rate nor the rate of long-term neurologic disabilities associated with preterm birth has declined. Increasing knowledge of the events leading to preterm birth and the pathophysiology of neonatal brain and lung injury suggests that the mortality and long-term impairments associated with these conditions will decrease. The large disparities in reproductive health and birth outcomes between industrialized and developing countries and between most other ethnic groups and blacks in the United States could be reduced by better access to already existing effective interventions.

Adult↗

Effect of smoking on serum concentrations of total homocysteine and B vitamins in mid-pregnancy.

There are conflicting findings in the literature on the effect of smoking on total homocysteine (tHcy) concentrations in non-pregnant subjects. We evaluated the effect of smoking on serum concentrations of tHcy, folate, vitamin B-12 pyridoxal 5'-phosphate (PLP, a coenzyme form of vitamin B-6) in 196 women at 18 and 30 weeks' gestation. The smokers were defined as those who self-reported cigarette smoking and had serum concentrations of thiocyanate, a biomaker of smoking, in the highest quartiles of the population. Mid-pregnancy serum tHcy concentrations were not significantly different between smokers and non-smokers. Folate, vitamin B-12 and PLP concentrations were generally lower in smokers than non-smokers. In smokers, tHcy concentrations had significant negative correlations with folate at both time points. The multiple regression analyses indicated that serum folate concentration was the most significant factor associated with tHcy concentrations among smokers, whereas thiocyanate concentrations showed no such effect. We conclude that serum tHcy concentrations were most strongly associated with the nutritional status of folate among the B vitamins tested during mid-pregnancy in our subjects. We suggest that it is essential to consider the nutritional status of folate, vitamin B-12 and vitamin B-6 in evaluating the effect of smoking on homocysteine metabolism.

Female↗

Vaginal fetal fibronectin levels and spontaneous preterm birth in symptomatic women.

OBJECTIVE: To relate vaginal fetal fibronectin levels in women with symptoms of preterm labor to subsequent spontaneous preterm birth. METHODS: Quantitative fetal fibronectin values were calculated from women who participated in two prospective multicenter trials relating fetal fibronectin to subsequent spontaneous preterm birth. The study populations consisted of women who presented with symptoms of preterm labor between 24(0)/(7) and 34(6)/(7) weeks, a singleton pregnancy, intact membranes, no prior tocolysis, and cervical dilation less than 3 cm. RESULTS: The characteristics of the two study populations were similar. In both populations, the rates of delivery within 7, 14, and 21 days after sampling were clustered into three distinct fetal fibronectin groups (less than 40, 40-100, and 100 ng/mL or more). As fetal fibronectin values increased, the risk of subsequent spontaneous preterm birth also increased. Delivery within 7 days of sampling was 0.4%, 3.3%, and 18.2% (trial A) and 1.4%, 8.0%, 30.0% (trial B) as the fetal fibronectin levels increased from less than 40 ng/mL, to 40-100 ng/mL, and to at least 100 ng/mL, respectively. CONCLUSION: In women with symptoms of preterm labor, an increase in fetal fibronectin from under 40 ng/mL, to 40-100 ng/mL, to at least 100 ng/mL was associated with a progressive increase in the risk of subsequent spontaneous preterm birth. The use of a single fetal fibronectin cutoff of 50 ng/mL for defining a positive test in women with symptoms of preterm labor should be reevaluated.

Adult↗

Repeated courses of antenatal corticosteroids.

A single course of corticosteroids given to women before an anticipated preterm birth reduces the incidence of respiratory distress syndrome, intraventricular hemorrhage, and neonatal death. For women who do not deliver within 1 week, repeated courses of corticosteroids have become common obstetric practice, despite little evidence of efficacy. Emerging data suggest little benefit and potential harm from that practice, so corticosteroids to improve perinatal outcomes should be restricted to a single course unless future randomized trial data prove additional courses to be beneficial.

Betamethasone↗

Evaluation of a new testing policy for human immunodeficiency virus to improve screening rates.

OBJECTIVE: To assess the effect of a change in human immunodeficiency virus (HIV) testing policy on HIV testing rates in an urban maternity clinic population. METHODS: Since 1995, our institution has provided pretest counseling and voluntary HIV testing to all pregnant women. After the 1999 Institute of Medicine recommendation of HIV testing with patient notification as a routine component of prenatal care, we conducted a prospective study to determine whether this policy would increase our HIV screening rates. The intervention incorporated HIV testing into the routine battery of tests drawn at antenatal care. Not to be tested required active refusal. The intervention group was comprised of all women receiving an initial antenatal visit in one of our eight maternity clinics between August 1, 1999, and July 30, 2000. The control group was comprised of all women presenting for prenatal care in the same clinics during the year before the intervention. RESULTS: The 3415 women in the intervention group and 3778 controls were similar with respect to most demographic and risk factors. After the intervention, HIV testing increased from 75% to 88% (P <.001). Among all women in both years of the study, women who were in the intervention group, less than 20 years of age, or who had a history of substance abuse, were more likely not to refuse testing. CONCLUSION: After implementation of a policy of routine HIV testing with active patient refusal, HIV testing rates increased among pregnant women in our large, urban obstetric clinic population.

AIDS Serodiagnosis↗

The Preterm Prediction Study: association between cervical interleukin 6 concentration and spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: The aim of this study was to determine the interrelationship between cervical concentration of interleukin 6 and detection of fetal fibronectin and other risk factors for spontaneous preterm birth. STUDY DESIGN: All patients with spontaneous preterm birth at <35 weeks' gestation (case patients; n = 125) and subjects matched for race, parity, and center delivered at > or = 37 weeks' gestation (n = 125; control subjects) were selected from women enrolled in the National Institute of Child Health and Human Development's Preterm Prediction Study. Interleukin 6 concentrations were determined by enzyme-linked immunosorbent assay in cervical swabs obtained at 22 weeks' to 24 weeks 6 days' gestation. Cutoffs to define an elevated interleukin 6 concentration included the 90th and 95th percentiles for control subjects (>305 and >538 pg/mL, respectively). RESULTS: The mean (+/-SD) interleukin 6 concentration was significantly higher in case patients than in control subjects (212 +/- 339 vs 111 +/- 186 pg/mL; P = .008). With either cutoff value elevated interleukin 6 concentration was significantly associated with spontaneous preterm birth (90th percentile, 20% vs 9.6%; P = .02; 95th percentile, 12% vs 4.8%; P = .04). Cervical interleukin 6 levels were highest within 4 weeks of delivery, and the trend continued until term. Elevated interleukin 6 concentration was not significantly associated with bacterial vaginosis, maternal body mass index <19.8 kg/m2, or a short cervix (< or = 25 mm), but it was significantly associated with a positive cervicovaginal fetal fibronectin test result (90th percentile, odds ratio, 5.5; 95% confidence interval, 2.6-11.9; 95th percentile, odds ratio, 5.3, 95% confidence interval, 2.1-12.9). The mean interleukin 6 concentration among women with a positive fibronectin test result was 373 +/- 406 pg/mL; that among women with a negative fetal fibronectin test result was 130 +/- 239 pg/mL (P = .001). In a regression analysis that adjusted for risk factors significantly associated with spontaneous preterm birth in this population (positive fetal fibronectin test result, body mass index <19.8 kg/m2, vaginal bleeding in the first or second trimester, previous spontaneous preterm birth, and short cervix) elevated cervical interleukin 6 concentration was not independently associated with spontaneous preterm birth (odds ratio, 1.8; 95% confidence interval, 0.8-4.3). CONCLUSIONS: At 24 weeks' gestation cervical interleukin 6 concentration in women who subsequently had a spontaneous preterm birth at <35 weeks' gestation was significantly elevated relative to those who were delivered at term. The association was particularly strong within 4 weeks of testing. A positive fetal fibronectin test result was strongly associated with elevated cervical interleukin 6 concentration, but bacterial vaginosis was not.

Case-Control Studies↗

Occupational fatigue and preterm premature rupture of membranes. National Institute of Child Health and Human Development Maternal-Fetal Medicine, Units Network.

OBJECTIVE: The aim of this study was to prospectively determine the relationship between occupational fatigue and spontaneous preterm delivery segregated into the etiologically distinct categories of spontaneous preterm labor, preterm premature rupture of membranes, and indicated preterm delivery. STUDY DESIGN: A total of 2929 women with singleton pregnancies at 22 to 24 weeks' gestation were enrolled in a multicenter (10 sites) Preterm Prediction Study. Patients reported the number of hours worked per week and answered specific questions designed to determine the following 5 sources of occupational fatigue described by Mamelle et al: posture, work with industrial machines, physical exertion, mental stress, and environmental stress. Fatigue was quantified (0-5 index) according to the number of these sources positively reported. Simple and Mantel-Haenszel chi2 tests were used to test the univariate association and hypothesis of a linear trend between sources of occupational fatigue and spontaneous preterm delivery. Covariables were considered by multivariate logistic regression analysis. Women who did not work outside the home were considered separately from those who worked but did not report any sources of occupational fatigue. RESULTS: Each source of occupational fatigue was independently associated with a significantly increased risk of preterm premature rupture of membranes among nulliparous women but not among multiparous women. The risk of preterm premature rupture of membranes increased (P = .002) with an increasing number of sources of occupational fatigue-not working outside the home, 2.1%; working but not reporting fatigue, 3.7%; working with 1 source of fatigue, 3.2%; working with 2 sources of fatigue, 5.2%; working with 3 sources of fatigue, 5.1%; and working with 4 or 5 sources of fatigue, 7.4%. There was also a significant relationship (P = .01) between preterm premature rupture of membranes and an increasing number of hours worked per week among nulliparous women. Neither spontaneous preterm labor nor indicated preterm delivery was significantly associated with occupational fatigue among either nulliparous or multiparous women. CONCLUSION: The occupational fatigue index of Mamelle et al discriminated a group of nulliparous women at increased risk for preterm premature rupture of membranes. The relationship between preterm premature rupture of membranes and occupational fatigue or hours worked may provide guidelines according to which nulliparous women and their employers can be advised.

Adolescent↗

The preterm prediction study: can low-risk women destined for spontaneous preterm birth be identified?

OBJECTIVE: Half of all preterm births occur in women without clinical risk factors. Our goal was to assess fetal fibronectin assay, Bishop score, and cervical ultrasonography as screening tests to predict which low-risk pregnancies will end in preterm birth. STUDY DESIGN: We performed a secondary analysis of data collected at 22 to 24 weeks' gestation from low-risk subjects enrolled in the Preterm Prediction Study, an observational study of risk factors for preterm birth conducted by the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Analysis was limited to primigravid women and to women who did not have a history of preterm birth or spontaneous pregnancy loss at <20 weeks' gestation. Bishop score (> or =4), fetal fibronectin level (> or =50 ng/mL), and cervical length (< or =25 mm) at 24 weeks' gestation were evaluated alone and in sequence as tests to predict spontaneous delivery before 35 weeks' gestation. RESULTS: Of the 2929 subjects enrolled in the original study, 2197 (1207 primigravid women and 900 low-risk multiparous women) met criteria for this analysis. There were 64 spontaneous births before 35 weeks' gestation (3.04%). All three tests were significantly related to birth before 35 weeks' gestation (high Bishop score: relative risk, 3.6; 95% confidence interval, 2.1-6.3; fetal fibronectin detection: relative risk, 8.2; 95% confidence interval, 4.8-13.9; short cervical length: relative risk, 6.9; 95% confidence interval, 4.3-11.1). However, the sensitivities of the tests alone were low (23.4% for high Bishop score, 23.4% for fetal fibronectin detection, and 39.1% for short cervix), as were the sensitivities for Bishop score followed by cervical ultrasonography (14.1%) and fetal fibronectin assay followed by cervical scan (15.6%). CONCLUSION: In the setting of low-risk pregnancy, fetal fibronectin assay and cervical ultrasonography have low sensitivity for preterm birth before 35 weeks' gestation. Sequential screening with Bishop score or fetal fibronectin assay followed by cervical ultrasonography further decreased sensitivity to only 15% among low-risk women.

Cervix Uteri↗

Midtrimester vaginal Mycoplasma genitalium in women with subsequent spontaneous preterm birth.

OBJECTIVE: We sought to determine the midtrimester prevalence of Mycoplasma genitalium in women who had subsequent spontaneous preterm birth. STUDY DESIGN: In a prospective study of lower genital tract infections, we identified 127 women who subsequently had spontaneous preterm birth. Vaginal samples were obtained between 21 and 25 weeks' gestation for pH, for bacterial vaginosis Gram stain, and cultures that yielded Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. M genitalium was identified by using validated polymerase chain reaction (PCR) primers, and the results were compared to pregnancy outcomes. RESULTS: Of 124 women with spontaneous preterm births, only five (3.9%) had PCR assays positive forM genitalium. The mean +/- SD delivery gestational age was similar for women with a positive PCR (34.6 +/- 2.2 weeks) and a negative PCR (34.0 +/- 2.7 weeks) (P =.62). None of the women with positive PCR results tested positive for any other sexually transmitted disease, whereas 36 (30%) women with negative PCR results tested positive. CONCLUSIONS: The occurrence of M genitalium in the vagina at midtrimester is infrequent in women with subsequent spontaneous preterm birth.

Animals↗

Metronidazole treatment of women with a positive fetal fibronectin test result.

Eighty-nine women with either bacterial vaginosis, Trichomonas vaginalis, or both, who also had a positive fetal fibronectin test result were randomized to two courses of metronidazole treatment as part of a Maternal-Fetal Medicine Network Units study of the National Institute of Child Health and Human Development. In this subgroup analysis, compared with the placebo group, women who were treated with metronidazole had a nonsignificant reduction in spontaneous preterm birth from 14.6% to 8.3%.

Anti-Infective Agents↗

The Preterm Prediction Study: toward a multiple-marker test for spontaneous preterm birth.

OBJECTIVE: The Preterm Prediction Study evaluated 28 potential biologic markers for spontaneous preterm birth in asymptomatic women at 23 to 24 weeks gestational age. This analysis compares those markers individually and in combination for an association with spontaneous preterm birth at <32 and <35 weeks gestational age. STUDY DESIGN: With the use of a nested case-control design from an original cohort study of 2929 women, results of tests from 50 women with a spontaneous preterm birth at <32 weeks and 127 women with a spontaneous preterm birth at <35 weeks were compared with results from matched-term control subjects. RESULTS: In the univariate analysis, the most potent markers that are associated with spontaneous preterm birth at <32 weeks by odds ratio were a positive cervical-vaginal fetal fibronectin test (odds ratio, 32.7) and <10th percentile cervical length (odds ratio, 5.8), and in serum, >90th percentiles of alpha-fetoprotein (odds ratio, 8.3) and alkaline phosphatase (odds ratio, 6.8), and >75th percentile of granulocyte colony-stimulating factor (odds ratio, 5.5). Results for spontaneous preterm birth at <35 weeks were generally similar but not as strong. Univariate and multivariate logistic regression analyses demonstrated little interaction among the tests in their association with spontaneous preterm birth. Combinations of the 5 markers were evaluated for their association with <32 weeks spontaneous preterm birth. Ninety-three percent of case patients had at least 1 positive test result versus 34% of control subjects (odds ratio, 24.0; 95% CI, 6.4-93.4). Among the case patients, 59% had >or=2 positive test results versus 2.4% of control subjects (odds ratio, 56.5; 95% CI, 7.1-451.7). If a cutoff of 3 positive test results was used, 20% of case patients and none of the control subjects had positive test results (P < .002). With the use of only the 3 serum tests (alkaline phosphatase, alpha-fetoprotein, and granulocyte colony-stimulating factor), any positive test identified 81% of cases versus 22% of control subjects (odds ratio, 14.7; 95% CI, 5.0-42.7). For spontaneous preterm birth at <35 weeks gestation, any 2 positive tests identified 43% of cases and 6% of control subjects (odds ratio, 11.2; 95% CI, 4.8-26.2). CONCLUSION: Overlap among the strongest biologic markers for spontaneous preterm birth is small. This suggests that the use of tests such as maternal serum alpha-fetoprotein, alkaline phosphatase, and granulocyte colony-stimulating factor as a group or adding their results to fetal fibronectin test and cervical length test results may enhance our ability to predict spontaneous preterm birth and that the development of a multiple-marker test for spontaneous preterm birth is feasible.

Alkaline Phosphatase↗

Plasma extracellular superoxide dismutase activity in healthy pregnant women is not influenced by zinc supplementation.

We hypothesized that plasma extracellular superoxide dismutase (EC-SOD) activity reflects the zinc nutriture of healthy pregnant women. Sixty-three women were selected from 580 African-American women who participated in a clinical trial to evaluate the effect of prenatal zinc supplementation on pregnancy outcome. Half of the women received zinc (25 mg/d) and the other half was given a placebo from about 19 wk gestation to delivery. In the trial, a positive effect of zinc supplementation on birthweight was observed, indicating that the population as a whole had suboptimal zinc nutriture. Using plasma samples obtained during the trial, EC-SOD activities were measured and the values were compared with plasma zinc concentrations and plasma alkaline phosphatase activities. Plasma EC-SOD activities in our subjects were lower than previously published values for healthy adults in Korea. Although plasma EC-SOD activity may reflect severe zinc deficiency, it is not a sensitive marker for marginal deficiency status. Plasma EC-SOD activities did not prove to be a better indicator of zinc nutriture of pregnant women than either plasma zinc or plasma alkaline phosphatase activities.

Alkaline Phosphatase↗