Robert C. Cefalo

Antibiotic treatment of preterm labor with intact membranes: A multicenter, randomized, double-blinded, placebo-controlled trial***

OBJECTIVE Although an association between subclinical intrauterine infection and preterm birth is well established, there is conflicting evidence regarding the benefits of antibiotic administration to women in preterm labor with intact membranes. We attempted to determine the effect of ampicillin-amoxicillin and erythromycin treatment on prolongation of pregnancy, the rate of preterm birth, and neonatal morbidity in patients with preterm labor and intact membranes. STUDY DESIGN A multicenter, randomized, double-blinded, placebo-controlled trial was designed and implemented by the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Two hundred seventy-seven women with singleton pregnancies and preterm labor with intact membranes (24 to 34 weeks) were randomly allocated to receive either antibiotics or placebos. RESULTS Of the 2373 patients screened for participation in this study in six medical centers, 277 women were enrolled (n = 133 for antibiotics group vs n = 144 for placebo group). In each study group, 60% of patients completed all the study medications. The overall prevalence of microbial invasion of the amniotic cavity was 5.8% (14/239). No significant difference between the antibiotic group and the placebo group was found in maternal outcomes, including duration of randomization-to-delivery interval, frequency of preterm delivery (< 37 weeks), frequency of preterm premature rupture of membranes, clinical chorioamnionitis, endometritis, and number of subsequent admissions for preterm labor. Similarly, no significant difference in neonatal outcomes could be detected between the two groups including respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and admission and duration of newborn intensive special care unit hospitalization. CONCLUSION The results of this study do not support the routine use of antibiotic administration to women in preterm labor with intact membranes.

Unexplained Elevations of Maternal Serum Alpha-fetoprotein

Alpha-fetoprotein (AFP) is a commonly used prenatal screening test for congenital anomalies. However, when anomalies are excluded after high resolution ultrasound and/or amniocentesis, an elevated maternal serum AFP (MSAFP) has been found to be associated with a 2- to 4-fold increase in low birthweight resulting from both preterm delivery and intrauterine growth retardation. Unexplained MSAFP elevations are also associated with up to 10-fold increase of placental abruption and a 10-fold increase in perinatal mortality. Results from studies of over 225,000 screened pregnancies indicate that 20 and 38 per cent of women with an unexplained MSAFP elevation may have an adverse pregnancy outcome. Twin gestations with MSAFP elevations greater than four multiples of the median are associated with similar constellations of pregnancy complications. Maternal serum AFP elevations in women with pregnancy complications are most likely the result of a leak of AFP across the placenta. Optimum management of women with unexplained elevations has not yet been established; however, evaluation of fetal growth throughout gestation is important in these patients.

Breast-feeding education of obstetrics-gynecology residents and practitioners☆

OBJECTIVE Our purpose was to assess breast-feeding education, knowledge, attitudes, and practices among resident and practicing obstetrician-gynecologists. STUDY DESIGN A mailed survey was administered to a national sample of resident and practicing obstetrician-gynecologists. RESULTS Response rates were 64% for residents and 69% for practitioners. Residency training included limited opportunity for direct patient interaction regarding breast-feeding; 60% of practitioners recommended that training devote more time to breast-feeding counseling skills. Only 38% of residents reported that obstetric faculty presented breast-feeding topics; more common sources were nursing staff and other residents. Practitioners rated themselves as more effective in meeting the needs of breast-feeding patients than were residents; prior personal breast-feeding experience was a significant influence on perceived effectiveness. Almost all respondents agreed that obstretician-gynecologists have a role in breast-feeding promotion, but significant deficits in knowledge of breast-feeding benefits and clinical management were found. CONCLUSION Residency training and continuing education programs should create opportunities to practice breast-feeding promotion skills and emphasize management of common lactation problems.

The effect of pregnancy on metabolic responses during rest, immersion, and aerobic exercise in the water

To examine the effects of advancing pregnancy on metabolic responses, 12 women, who were recruited early in pregnancy, were studied during 20 minutes of immersion in 30 degrees C water, followed by 20 minutes of exercise in the water (60% of predicted maximal capacity) and 20 minutes of lateral supine recovery. Each subject completed the trials during the fifteenth, twenty-fifth, and thirty-fifth weeks of pregnancy, as well as a control period 8 to 10 weeks post partum. Resting oxygen uptake increased with advancing pregnancy. Resting oxygen uptake was higher in the water than on land but was not altered by pregnancy. Exercise oxygen uptakes were similar for all trials, but the work load required to elicit the VO2 decreased during the thirty-fifth week of pregnancy. Exercise heart rates followed the same pattern as oxygen uptake. Lactate concentrations declined with advancing pregnancy after exercise. Blood glucose levels were normal for pregnancy but declined slightly during exercise. Blood triglyceride levels were elevated with exercise, with a tendency to increase with advancing pregnancy. Resting plasma cortisol concentrations increased with pregnancy but remained lower during immersion and exercise. These results suggest that pregnancy significantly alters metabolic responses to exercise in the water.

The clinical content of preconception care: alcohol, tobacco, and illicit drug exposures

Substance abuse poses significant health risks to childbearing-aged women in the United States and, for those who become pregnant, to their children. Alcohol is the most prevalent substance consumed by childbearing-aged women, followed by tobacco, and a variety of illicit drugs. Substance use in the preconception period predicts substance use during the prenatal period. Evidence-based methods for screening and intervening on harmful consumption patterns of these substances have been developed and are recommended for use in primary care settings for women who are pregnant, planning a pregnancy, or at risk for becoming pregnant. This report describes the scope of substance abuse in the target population and provides recommendations from the Clinical Working Group of the Select Panel on Preconception Care, Centers for Disease Control and Prevention, for addressing alcohol, tobacco, and illicit drug use among childbearing-aged women.

The clinical content of preconception care: infectious diseases in preconception care.

A number of infectious diseases should be considered for inclusion as part of clinical preconception care. Those infections strongly recommended for health promotion messages and risk assessment or for the initiation of interventions include Chlamydia infection, syphilis, and HIV. For selected populations, the inclusion of interventions for tuberculosis, gonorrheal infection, and herpes simplex virus are recommended. No clear evidence exists for the specific inclusion in preconception care of hepatitis C, toxoplasmosis, cytomegalovirus, listeriosis, malaria, periodontal disease, and bacterial vaginosis (in those with a previous preterm birth). Some infections that have important consequences during pregnancy, such as bacterial vaginosis (in those with no history of preterm birth), asymptomatic bacteriuria, parvovirus, and group B streptococcus infection, most likely would not be improved through intervention in the preconception time frame.

The Pharmacokinetics of Recombinant Human Relaxin in Nonpregnant Women After Intravenous, Intravaginal, and Intracervical Administration

The pharmacokinetics of recombinant human relaxin (rhRlx) after intravenous (iv) bolus administration and the absorption of rhRlx after intracervical or intravaginal administration were determined in nonpregnant women. The study was conducted in two parts. In part I, 25 women received 0.01 mg/kg rhRlx iv. After a minimum 7-day washout period, these women were dosed intracervically (n = 10) or intravaginally (n = 15) with 0.75 or 1.5 mg rhRlx, respectively, in 3% methylcellulose gel. Part II was a double-blind, randomized, three-way crossover study in 26 women. At 1-month intervals, each woman received one of three intravaginal treatments consisting of 0 (placebo), 1, or 6 mg rhRlx in 3% methylcellulose gel. The serum concentrations of relaxin following iv administration were described as the sum of three exponentials. The mean (±SD) initial, intermediate, and terminal half-lives were 0.09 ± 0.04, 0.72 ± 0.11, and 4.6 ± 1.2 hr, respectively. Most of the area under the curve was associated with the intermediate half-life. The weight-normalized clearance was 170 ± 50 mL/hr/kg. The observed peak concentration was 98 ± 29 ng/mL, and the weight-normalized initial volume of distribution was 78 ± 40 mL/kg, which is approximately equivalent to the serum volume. If central compartment elimination was assumed, the volume of distribution at steady state (Vss/W) was 280 ± 100 mL/kg, which is approximately equivalent to extracellular fluid volume. Vss/W could be as large as 1300 ± 400 mL/kg without this assumption. After intravaginal administration of the placebo gel, endogenous relaxin concentrations were evident (i.e., ≥20 pg/mL) in 9 of the 26 women (maximum concentrations, 23–234 pg/mL). A similar proportion of women (approximately 35–40%) exhibited measurable serum concentrations of relaxin following intravaginal rhRlx treatment; this proportion increased to 90% following intracervical rhRlx treatment. For both routes of administration, the maximum serum concentrations of relaxin were usually within the range of values observed for endogenous relaxin, suggesting that the absorption of rhRlx was minimal.

Disseminated herpes simplex in pregnancy: two cases and a review.

Documented disseminated infection with herpes simplex virus has been reported only five times in pregnancy. All cases have been severe and demonstrated common clinical features, including hepatitis and adenopathy. These reports are reviewed and two new cases added. Dissemination is undoubtedly more common, and commonly less dramatic in presentation then previously suspected. Hepatocellular dysfunction and generalized adenopathy should be clues to dissemination. Dissemination has occurred only in the second half of pregnancy, and even with infected amniotic fluid, has not always resulted in an infected infant. Transplacental maternal IGG has been documented, but is not protective, though newer antiviral drugs do show therapeutic potential. The clinician should be aware of the possibility of dissemination in any patient with oral or genital herpes and generalized signs or symptoms of disease.

Preconceptional health care model

During the last 10 years, there has been a movement to expand the definition of prenatal care to encompass preconceptional counseling. Major organizations throughout the world have endorsed preconceptional counseling as an integral component of care for all women contemplating pregnancy. This article will assist health care providers who interact with women of reproductive age to understand the potential benefits and limitations of preconceptional counseling and to develop an approach to that service relating to nutrition, infections, and metabolic diseases as they impact on reproductive outcome. Although there are many potential benefits of the preconception health care model, barriers to its implementation remain.

Amniotic fluid embolism. Three case reports with a review of the literature.

Amniotic fluid embolism is a catastrophic event of the intra- and early postpartum period which may also be seen with cesarean delivery and during abortions. Presenting symptomatology includes respiratory distress with cyanosis, shock, and possibly tonic-clonic seizures. DIC frequently occurs. The pathogenesis may include entry of amniotic fluid through lacerations or ruptures of the uterus or cervix, through endocervical veins and through abnormal uteroplacental sites, such as with placental abruption, placenta previa, or placenta accreta. Amniotic fluid probably causes cardiovascular-respiratory symptoms by pulmonary vascular obstruction and through a vasoactive substance causing pulmonary vascular constriction. The lethality of amniotic fluid may be enhanced by a high particulate content or meconium staining. The diagnosis of amniotic fluid embolism may be made ante mortem by demonstrating amniotic fluid debris in central blood samples or expectorated sputum. Postmortem diagnosis often requires meticulous examination of the pulmonary microvasculature with the utilization of special stains. Treatment is directed towards symptoms of shock, arterial hypoxemia, and DIC. Acute renal failure may complicate the picture after shock. If the patient survives the embolic and coagulative problems, recovery is usually complete without long-term sequelae.