Garland D. Anderson

Drug abuse and other risk factors for physical abuse in pregnancy among white non-Hispanic, black, and Hispanic women

We investigated prevalence and risk factors associated with physical abuse among a tricultural population of 501 pregnant women who attended a public prenatal clinic. Twenty percent (98/501) reported being physically abused; 29% (28/98) stated that abuse occurred during pregnancy. More white non-Hispanic women reported previous abuse than did black or Hispanic women. Battered women more frequently were divorced or separated, were of greater parity, smoked, used alcohol, or admitted to illicit drug use than did women who were not battered. An increased risk of previous physical abuse was observed among white non-Hispanic and black women who used alcohol (odds ratios = 3.0 and 6.0) or drugs (odds ratios = 2.1 and 3.7) but not among Hispanic women. Odds ratios of 4.7 for cocaine use among white non-Hispanic women, 4.7 for marijuana use among black women, and 5.8 for tobacco use among Hispanic women were observed. This is the first study to report the effects of race on the association between physical abuse of pregnant women and substance use.

First-trimester prediction of preeclampsia in nulliparous women at low risk

OBJECTIVE: To identify clinical characteristics and biochemical markers in first-trimester samples that would possibly predict the subsequent development of preeclampsia. METHODS: We conducted a multicenter observational study in 2,434 nulliparous women at low risk to identify biomarkers that possibly predict preeclampsia. Clinical history, complete blood count, and biochemical markers were assessed in the first trimester. The trophoblast and angiogenesis markers ADAM-12, pregnancy-associated plasma protein-A, placental protein 13, placental growth factor, soluble fms-like tyrosine kinase-1, and endoglin were measured in a case-control subset of 174 women with preeclampsia and 509 women in the control group. RESULTS: Univariable analysis revealed maternal age, race, marital status, years of education, source of medical payment, prenatal caregiver, body mass index (BMI, calculated as weight (kg)/[height (m)]2), and systolic blood pressure at enrollment were significantly associated with preeclampsia. Mean platelet volume was greater at enrollment in women who later had development of preeclampsia (median 9.4 compared with 9.0 femtoliter (fl); P=.02). First-trimester concentrations (multiples of the median) of ADAM-12 (1.14 compared with 1.04; P=.003), pregnancy-associated plasma protein-A (0.94 compared with 0.98; P=.04), and placental growth factor (0.83 compared with 1.04; P<.001) were significantly different in women who had development of preeclampsia compared with women in the control group. The optimal multivariable model included African American race, systolic blood pressure, BMI, education level, ADAM-12, pregnancy-associated plasma protein-A, and placental growth factor, and yielded an area under the curve of 0.73 (95% confidence interval 0.69–0.77) and a sensitivity of 46.1% (95% confidence interval 38.3–54.0) for 80% specificity. CONCLUSION: A multivariable analysis of clinical data and biochemical markers in the first trimester did not identify a model that had clinical utility for predicting preeclampsia in a nulliparous population at low risk. LEVEL OF EVIDENCE: II

Immunoreactive calcitonin in the mother, neonate, child, and adult

Immunoreactive calcitonin (iCT) was measured in umbilical arterial and venous blood and in maternal peripheral blood in 32 normal deliveries. The results were compared with values found in nonpregnant adult females. The umbilical arterial blood contained significantly higher concentrations of iCT than umbilical venous blood (p less than 0.001). The serum iCT in maternal peripheral blood was significantly higher than in normal nonpregnant subjects (p less than 0.001). Serum iCT was also measured in 342 male and female subjects ranging in age from 1 hour to 60 years. Serum iCT was found to be high early in life and to diminish with age. Our data suggest that calcitonin may be of physiologic significance in bone formation during intrauterine life and childhood. High serum iCT may also be responsible for the hypocalcemia seen in the neonatal period.

Prevention of preterm birth in triplets using 17 alpha-hydroxyprogesterone caproate: A randomized controlled trial

OBJECTIVE: To assess whether 17 alpha-hydroxyprogesterone caproate reduces the rate of preterm birth in women carrying triplets. METHODS: We performed this randomized, double-blinded, placebo-controlled trial in 14 centers. Healthy women with triplets were randomly assigned to weekly intramuscular injections of either 250 mg of 17 alpha-hydroxyprogesterone caproate or matching placebo, starting at 16–20 weeks and ending at delivery or 35 weeks of gestation. The primary study outcome was delivery or fetal loss before 35 weeks. RESULTS: One hundred thirty-four women were assigned, 71 to 17 alpha-hydroxyprogesterone caproate and 63 to placebo; none were lost to follow-up. Baseline demographic data were similar in the two groups. The proportion of women experiencing the primary outcome (a composite of delivery or fetal loss before 35 0/7 weeks) was similar in the two treatment groups: 83% of pregnancies in the 17 alpha-hydroxyprogesterone caproate group and 84% in the placebo group, relative risk 1.0, 95% confidence interval 0.9–1.1. The lack of benefit of 17 alpha-hydroxyprogesterone caproate was evident regardless of the conception method or whether a gestational age cutoff for delivery was set at 32 or 28 weeks. CONCLUSION: Treatment with 17 alpha-hydroxyprogesterone caproate did not reduce the rate of preterm birth in women with triplet gestations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00099164 LEVEL OF EVIDENCE: I

The relationship between maternal glycemia and perinatal outcome.

OBJECTIVE: To examine the relationship between varying degrees of maternal hyperglycemia and pregnancy outcomes. METHODS: This was a secondary analysis of a treatment trial for mild gestational diabetes including four cohorts: 1) 473 women with untreated mild gestational diabetes; 2) 256 women with a positive 50-g screen and one abnormal oral glucose tolerance test (OGTT) value; 3) 675 women with a positive screen and no abnormal OGTT values; and 4) 437 women with a normal 50-g screen. Groups were compared by test of trend for a composite perinatal outcome (neonatal hypoglycemia, hyperbilirubinemia, elevated cord C-peptide level, and perinatal trauma or death), frequency of large for gestational age neonates, shoulder dystocia, and pregnancy-related hypertension. Three-hour OGTT levels (fasting, 1-, 2-, and 3-hour) levels were divided into categories and analyzed for their relationship to perinatal and maternal outcomes. RESULTS: There were significant trends by glycemic status among the four cohorts for the composite and all other outcomes (P<.001). Analysis for trend according to OGTT categories showed an increasing relationship between fasting and all postload levels and the various outcomes (P<.05). Fasting glucose 90 mg/dL or greater and 1 hour 165 mg/dL or greater were associated with an increased risk for the composite outcome (odds ratios and 95% confidence intervals of 2.0 [1.03–4.15] and 1.46 [1.02–2.11] to 1.52 [1.08–2.15] for the fasting and 1 hour, respectively). A 1 hour glucose 150 mg/dL or greater was associated with an increased risk for large for gestational age (odds ratios, 1.8 [1.02–3.18] to 2.35 [1.35–4.14]); however, 2- and 3-hour glucose levels did not increase the risk for the composite or large for gestational age until well beyond current gestational diabetes diagnostic thresholds. CONCLUSION: A monotonic relationship exists between increasing maternal glycemia and perinatal morbidity. Current OGTT criteria require reevaluation in determining thresholds for the diagnosis and treatment of gestational diabetes. LEVEL OF EVIDENCE: II

Neonatal Organ System Injury in Acute Birth Asphyxia Sufficient to Result in Neonatal Encephalopathy

OBJECTIVE To identify the proportion of major organ system injury in cases of acute intrapartum asphyxia that result in neonatal encephalopathy. METHODS A prospectively maintained database was cross‐referenced using medical record coding to identify diagnoses of acute intrapartum asphyxia, acute birth asphyxia, or neonatal encephalopathy over a 6‐year period. An acute intrapartum asphyxial antecedent was validated with emphasis on excluding long‐standing or chronic conditions where injury likely occurred before presentation. Injury pattern was evaluated using routinely available laboratory and imaging tests. RESULTS Forty‐six cases of acute peripartum asphyxia sufficient to result in the diagnosis of neonatal encephalopathy were identified. Clinical central nervous system injury resulting in encephalopathy was present in 100% of cases as it was an entry criteria; of these, 49% had electroencephalogram and 40% had imaging studies diagnostic of acute injury. Liver injury based on elevated aspartate transaminase or alanine transaminase levels occurred in 80%. Heart injury, as defined by pressor or volume support beyond 2 hours of life or elevated cardiac enzymes, occurred in 78%. Renal injury, defined by an elevation of serum creatinine to greater than 1.0 mg/dL, persistent hematuria, persistent proteinuria, or clinical oliguria, occurred in 72%. An elevation in nucleated red blood cell counts exceeding 26 per 100 white blood cells occurred in 41%. CONCLUSION Using common diagnostic tests as markers of acute asphyxial injury, we noted that multiple organs suffer damage during an acute intrapartum asphyxial event sufficient to result in a neonatal encephalopathy.

Second-stage labor duration in nulliparous women: relationship to maternal and perinatal outcomes

OBJECTIVE The purpose of this study was to assess maternal and perinatal outcomes as a function of second-stage labor duration. STUDY DESIGN We assessed outcomes in nulliparous laboring women who were enrolled in a trial of fetal pulse oximetry. RESULTS Of 5341 participants, 4126 women reached the second stage of labor. As the duration of the second stage increased, spontaneous vaginal delivery rates declined, from 85% when the duration was <1 hour to 9% when it was > or =5 hours. Adverse maternal outcomes that were associated significantly with the duration of the second stage of labor included chorioamnionitis (overall rate, 3.9%), third- or fourth-degree perineal laceration (overall rate, 8.7%), and uterine atony (overall rate, 3.9%). Odds ratios for each additional hour of the second stage of labor ranged from 1.3-1.8. Among individual adverse neonatal outcomes, only admission to a neonatal intensive care unit was associated significantly with second stage duration (odds ratio, 1.4). CONCLUSION The second stage of labor does not need to be terminated for duration alone.

Follow-up of Children Exposed In Utero to 17 α-Hydroxyprogesterone Caproate Compared With Placebo

OBJECTIVE: To assess whether there are evident adverse effects of 17 &agr;-hydroxyprogesterone caproate after in utero exposure. METHODS: This study evaluated surviving children of mothers who participated in a multicenter placebo-controlled trial of weekly intramuscular 17 &agr;-hydroxyprogesterone caproate, with a 2:1 allocation to 17 &agr;-hydroxyprogesterone caproate and placebo, respectively. The guardian was interviewed about the child’s general health. Children underwent a physical examination and developmental screen with the Ages and Stages Questionnaire. Gender-specific roles were assessed with the Preschool Activities Inventory. RESULTS: Of 348 eligible surviving children, 278 (80%) were available for evaluation (194 in the 17 &agr;-hydroxyprogesterone caproate group and 84 in the placebo group). The mean age at follow-up was 48 months. No significant differences were seen in health status or physical examination, including genital anomalies, between 17 &agr;-hydroxyprogesterone caproate and placebo children. Scores for gender-specific roles (Preschool Activities Inventory) were within the normal range and similar between 17 &agr;-hydroxyprogesterone caproate and placebo groups. CONCLUSION: 17 &agr;-hydroxyprogesterone caproate seems to be safe for the fetus when administered in the second and third trimesters. LEVEL OF EVIDENCE: II

The use of medroxyprogesterone acetate for relief of climacteric symtoms

Climacteric symptoms in the menopausal woman are perplexing to the physician. Recent literature concerning the relationship of estrogen to carcinogenesis has caused many women to discontinue this medication; thus, there is a need for an alternative therapy for the relief of these symptoms. The drug medroxyprogesterone acetate (Depo-Provera) was assessed in a double-blind, randomized, placebo-controlled study involving 48 subjects. Only one of the placebo-treated patients claimed any relief from climacteric symptoms while only two of the patients who received the study drug noted little or no relief (P < 0.0001). Relief from climacteric symptoms began at 4 to 7 days after entry into the study and extended for 8 to 20 weeks. The only side effects were withdrawal bleeding and a slight, transient weight gain. Depo-Provera appears to be a reliable substitute for estrogen in the treatment of climacteric symptoms. Further investigations with this medication seem indicated.

Omega-3 Fatty Acid Supplementation to Prevent Recurrent Preterm Birth: A Randomized Controlled Trial

OBJECTIVE: To assess whether the addition of an omega-3 long-chain polyunsaturated fatty acid supplement would reduce preterm birth in women with at least one prior spontaneous preterm birth receiving 17&agr;-hydroxyprogesterone caproate. METHODS: We conducted a randomized, double-masked, placebo-controlled trial in 13 centers. Women with a history of prior spontaneous singleton preterm birth and a current singleton gestation were assigned to either a daily omega-3 supplement (1,200 mg eicosapentaenoic acid and 800 mg docosahexaenoic acid) or matching placebo from 16-22 through 36 weeks of gestation. All participants received weekly intramuscular 17&agr;-hydroxyprogesterone caproate (250 mg). The primary study outcome was delivery before 37 weeks of gestation. A sample size of 800 was necessary to have 80% power to detect a 30% reduction in the primary outcome from 30%, assuming a type I error two-sided of 5%. RESULTS: A total of 852 women were included, and none was lost to follow up. Delivery before 37 weeks of gestation occurred in 37.8% (164/434) of women in the omega-3 group and 41.6% (174/418) in the placebo group (relative risk 0.91, 95% confidence interval 0.77-1.07). CONCLUSION: Omega-3 long-chain polyunsaturated fatty acid supplementation offered no benefit in reducing preterm birth among women receiving 17&agr;-hydroxyprogesterone caproate who have a history of preterm delivery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00135902. LEVEL OF EVIDENCE: I