Tocolysis in women with advanced preterm labor: a secondary analysis of a randomized clinical trial.

OBJECTIVE: To compare the efficacy of tocolytic treatment with indomethacin (I), magnesium sulfate (M) and nifedipine (N) for acute tocolysis in women with advanced cervical dilation (4-6 cm). METHODS: A single center, randomized trial was carried out involving patients in preterm labor (cervix 1-6 cm). Secondary analysis of women with advanced cervical dilation (cervix 4-6 cm) at 24-32 weeks' gestation who received intravenous M, oral N or I suppositories comprised this study population. RESULTS: Over 38 months, 92 women with advanced cervical dilation were randomized to one tocoloytic type. Days gained in utero (11.7) and percent remaining undelivered at 48 h (60.8%), 72 h (53.1%) and >7 days (38.3%) were similar regardless of tocolytic employed (p = 0.923, 0.968, 0.791, 0.802, respectively). Likewise, gestational age at delivery (30.7 ± 3.2) was similar between groups (p = 0.771). Finally, neonatal statistics were not different when stratified by tocolytic treatment. CONCLUSION: There were no statistical differences between tocolytics in treating women with advanced cervical dilation. All offered significant days gained in utero after therapy, a high percentage remaining undelivered after 48 or 72 h and after 7 days. It would appear from data that there may be advantages to tocolytic treatment even in women with advanced cervical dilation.

The use of 17-hydroxy progesterone in women with arrested preterm labor: a randomized clinical trial.

BACKGROUND: The use of 17-alpha-hydroxyprogesterone caproate (17 P) has been shown to reduce preterm delivery in women who have had a prior preterm birth. The role of 17 P in women with arrested preterm labor is less certain. AIMS: To compare the preterm birth rate and neonatal outcome in women with arrested preterm labor randomized to receive 17 P or placebo. MATERIALS AND METHODS: Women with arrested preterm labor were randomized to weekly injections of either 17 P (250 mg) or placebo. Maternal and neonatal outcome were evaluated. RESULTS: Forty-five singleton pregnancies were randomized after successful tocolysis; 22 received 17 P while 23 got placebo. Gestational age at delivery (p = 0.067) and the interval from treatment to delivery (p = 0.233) were not affected by 17 P. Significantly less women in the 17 P group delivered at <34 weeks (14 versus 21, p = 0.035). There was also a significant reduction in the risk of neonatal sepsis (p = 0.047) and gr III/IV intraventricular hemorrhage (IVH) (p = 0.022) in the 17 P group. CONCLUSION: In this study, 17 P did not delay the interval to delivery after successful preterm labor, but births <34 weeks as well as neonatal sepsis and IVH were reduced by 17 P treatment.

A comparison of three tocolytics for preterm labor: a randomized clinical trial.

OBJECTIVE: To compare the efficacy and maternal side effects of nifedipine (N), magnesium sulfate (M), and indomethacin (I) for acute tocolysis. METHODS: In this single center randomized trial, women in preterm labor 24-32 weeks' gestation received intravenous M, oral N, or I suppositories. The primary outcomes of interest were arrest of preterm labor (>48 h, ≥7 days), gestational age at delivery, and maternal side effects. RESULTS: Over a 38-month period, 301 women were allocated to receive M (90), N (114), or I (90). Gestational age at delivery (p = 0.551) or arrest of labor >48 h, >7 days were similar between the three groups (p = 0.199, 0.654). Hypotension and tachycardia were more common in N patients compared to women receiving M or I (p = 0.003, 0.009). Patients receiving I had more fetal ductal constriction or oligohydramnios compared to M or N (p = 0.001, 0.020) but, I women were tested more often. There was one case of pulmonary edema in the M group and one with plural effusion in the N group. CONCLUSION: There were no differences in efficacy or in major maternal safety issues between the three tocolytic agents. Since there is no FDA approved tocolytic to treat preterm labor, clinicians should use the tocolytic that has afforded them the best results with the least maternal/neonatal side effects.

Postpartum thrombotic microangiopathic syndrome.

OBJECTIVE: Characterization of syndromes for patients with life-threatening, progressively worsening hemolysis-elevated-liver-enzymes-and-platelet (HELLP) syndrome-like diseases and with thrombotic microangiopathies. RETROSPECTIVE STUDY DESIGN: Patients who underwent postpartum plasma-exchange (PPEX) for preeclampsia-related, and microangiopathy/coagulopathy illnesses unresponsive to medical therapy between 1994 and 2008 in our center and elsewhere. RESULTS: Nine patients were treated with PPEX in our center with 78% maternal survival. Treatment with PPEX increased platelet levels (p=0.048), decreased serum lactic dehydrogenase (p=0.0012) and aspartate aminotransferase (p=0.0001). CONCLUSION: Nineteen patients from publications combined with our patients suggest five categories of postpartum thrombotic microangiopathy syndrome that exhibit HELLP syndrome criteria and respond to PPEX.

Effect of antenatal tocolysis on neonatal outcomes.

OBJECTIVE: Detail adverse neonatal effects in pregnancies treated with indomethacin (I), magnesium sulfate (M) or nifedipine (N). METHODS: Women in acute preterm labor with cervical dilatation 1-6 cm were randomized to receive one of three first-line tocolytic drugs. RESULTS: There were 317 neonates (I = 103, M = 95, N = 119) whose mothers were treated with tocolytic therapy. There was no difference in gestational age at randomization (average 28.6 weeks' gestation) or at delivery (31.6 weeks' gestation, p = 0.551), birth weight (p = 0.871) or ventilator days (p = 0.089) between the three groups. Neonatal morbidity was not different between the three groups; respiratory distress syndrome (p = 0.086), patent ductus arteriosus (p = 0.592), sepsis (p = 0.590), necrotizing enterocolitis (p = 0.770), intraventricular hemorrhage (p = 0.669) and periventricular leukomalacia (p = 0.124). CONCLUSIONS: There were no statistically significant differences between the three tocolytics as far as composite neonatal morbidity or mortality was concerned.

Women with preterm premature rupture of the membranes do not benefit from weekly progesterone.

OBJECTIVE: We sought to determine if 17-alpha-hydroxyprogesterone (17P) extends gestation vs placebo in women with preterm premature rupture of the membranes (PPROM). STUDY DESIGN: Women with vertex presentations with PPROM, 20-30 weeks' gestation, were randomized to receive weekly 17P or placebo in an attempt to prolong the pregnancy. A total of 69 patients (17P, n = 33; placebo, n = 36) were randomized into this study. RESULTS: Initial cervical dilatation, gestational age at enrollment, and interval to delivery were not different between the 2 groups (P = .914, .424, and .146, respectively). Time of randomization to delivery (P = .250), mode of delivery (relative risk, 1.16; 95% confidence interval, 0.66-2.06), and the neonatal outcome statistics of morbidity (P = .820) and mortality (relative risk, 1.28; 95% confidence interval, 0.59-2.75) were similar between the 2 groups. CONCLUSION: In patients with PPROM, 17P did not extend gestation vs placebo and cannot be recommended for treatment in such women.

Prediction of placenta accreta by ultrasonography and color Doppler imaging.

OBJECTIVE: To determine the accuracy of ultrasound and color flow Doppler to diagnose placenta accreta. METHODS: Respectively, ultrasound images consistent with signs of placenta accreta (concomitant previa, numerous vascular lacunae, absent lower uterine segment between bladder-placenta, turbulent or complicated blood flow at the uteroplacental interface) were correlated with findings at the time of surgery and pathologic examination. RESULTS: Over 64 months, 12 cases with suspected placenta accreta by ultrasound were studied. The median gestational age at first diagnosis was 25 weeks and 92% had a previa while all had at least one previous cesarean delivery. At surgery, 83% (10/12) had an adherent placenta requiring hysterectomy (eight accreta, one increta, and one percreta). There were two false positives (one complete previa, one low-lying placenta with vasa previa). Nine of 12 women (75%) required blood transfusions due to a mean hematocrit nadir of 22.7 ± 4.6%. The mean number of packed red blood cell units transfused was 4.9 ± 4.7 units (range 2-17 units). CONCLUSION: Sonography coupled with color-flow Doppler appears helpful in allowing antenatal diagnosis of accreta.

Progesterone does not prevent preterm births in women with twins.

OBJECTIVE: To compare preterm birth rate and neonatal outcome in twin gestations randomized to either 17 alpha-hydroxyprogesterone caproate (17P) or placebo. MATERIALS AND METHODS: Women with twin gestations between 20-30 weeks were randomized to receive weekly injections of either 250 mg 17P injection (Group I), or placebo (Group II). Maternal and neonatal outcome data was recorded. RESULTS: Thirty twin intrauterine pregnancies were randomized; 16 received 17P and 14 received placebo. Demographic data as well as past history and gestational age at randomization were equivalent between groups (P = 0.286-0.847). All patients in both groups were Medicaid recipients. The incidence of preterm labor (P = 0.980), and premature rupture of the membranes (P = 0.525) were the same between groups. Gestational age at delivery was also similar between 17P (33.9 weeks) versus placebo (33.1 weeks, P = 0.190) as was the incidence of preterm birth <35 weeks (44% vs 79%, P = 0.117). Infant weight (P = 0.641), Apgar score at 5 minutes (P = 0.338) as well as neonatal morbidity such as respiratory distress syndrome (P = 0.838), patent ductus arteriosus (P = 0.704), intraventricular hemorrhage (P = 0.851) and necrotizing enterocolitis (P = 0.946) showed no difference. Days spent in the NICU among 17P (18.4) versus placebo (17.3, P = 0.155), neonatal death (P = 0.359) and those infants discharged with neurologic handicap (P = 0.594) were not different between groups. CONCLUSION: Amongst this group of twin gestations weekly 17HP injections did not reduce the incidence of preterm birth or the complications associated with prematurity.

Pregnancy loss after first trimester viability in women with sickle cell trait: a preliminary report.

BACKGROUND: Traditionally, sickle cell trait has not been associated with a higher risk of fetal death, but we noted several, which led us to assess all such pregnancies. METHODS: In this retrospective study, 131 patients with sickle cell trait were analyzed over a two-year period. The Institutional Review Board approved the collection of deidentified data. RESULTS: Subjects were African-American with an average age of 23.9 years, and average gestational age at delivery of 30.1 weeks. There were 10 (8.13%) intrauterine fetal deaths (IUFDs), and one neonatal death. Ascending amniotic fluid infection was noted in 50% and 92% meconium histocytes. All placentas had sickling in the intervillous space and the decidual vessels. CONCLUSIONS: Sickling in the decidual vessels and poor placental perfusion may play a role in pregnancy loss in excess of what has previously been reported. A cohort control study appears to be in order. NARRATIVE: Pregnant women with sickle cell trait are thought not to have increased maternal or fetal mortality/morbidity. Over a two year period, we studied 131 women with this hemoglobinopathy and found that 10.6% had intrauterine growth retardation (IUGR), 8.4% preterm premature rupture of the membranes, 8.1% intrauterine fetal demise (n = 10) at most occurring at 16 to 24 weeks, and one neonatal death. Amniotic fluid infection was noted in 50%, and meconium histocytes indicating intrauterine hypoxia were noted, as was unsuspected sickling in the placental vasculature. Based on this case series, sickle cell trait may not be as benign for the fetus as was previously thought.

Metformin and insulin in the management of gestational diabetes mellitus: preliminary results of a comparison.

OBJECTIVE: To compare glycemic control and neonatal outcomes in women with gestational diabetes mellitus (GDM) treated with metformin vs. insulin. STUDY DESIGN: Women with GDM not controlled with diet and exercise were randomized to metformin (n = 32) or insulin (n = 31). The levels of glycemic control as well as maternal/neonatal complications were evaluated. RESULTS: The mean (+/- SD) fasting and 2-hour postprandial blood glucose did not differ statistically between the 2 treatment groups. No patient failed metformin and required insulin. The majority (27/32) were easily controlled on the initial dosage (500 mg twice a day). Gestational age at entry and delivery (p = 0.077, 0.412) were similar. The difference in the rate of cesarean delivery was not statistically significant between the 2 groups (p = 0.102). Neonatal statistics were also not different between the metformin and insulin groups: birth weight, Apgar score at 5 minutes, respiratory distress syndrome, hyperbilirubinemia, neonatal hypoglycemia and neonatal intensive care unit admission (p = 0.144-0.373). CONCLUSION: Based on these preliminary data, metformin appears to be an effective alternative to insulin in the treatment of GDM.

Tocolytic preference for treatment of preterm labor.

Preterm labor remains the most common complication of pregnancy. Although tocolytic treatment is the standard of care in such women, there is no FDA approved drug for therapy, and there is no unanimity of drug regimens among physicians. This survey details the patterns of twenty Maternal-Fetal Medicine specialists who manage over 6,000 cases of preterm labor with intact membranes annually. Approximately 90% of women were seen early enough to be effectively treated with tocolytics, and over 90% of these subjects received corticosteroids. First-line tocolytic use favored magnesium sulfate while antiprostaglandin drugs were the leading second-line drug whereas intravenous terbutaline and calcium channel antagonists were used less often. There were many different dosage patterns for each drug as well as combinations of various tocolytic drugs which were individually adjusted for patient circumstances. Women with preterm labor and intact membranes are usually treated with tocolytics and corticosteroids, but regimens are varied and all use is off label. This study demonstrates the need for an FDA approved tocolytic which could be used consistently for such women.

Non-immune hydrops fetalis: prenatal diagnosis and perinatal outcomes.

PURPOSE: To describe the perinatal outcomes after a prenatal diagnosis of non-immune hydrops fetalis (NIHF). METHODS: Retrospective case series. University of Mississippi ultrasound database from July 2000 to January 2003 was reviewed for cases of NIHF. Records abstracted for maternal demographics and neonatal outcomes. RESULTS: Thirty-one cases of NIHF were identified and full data was available for 29 cases. Median gestational age at diagnosis was 17.3 weeks. Structural fetal malformations were noted in 22 cases (76%); most common were cystic hygroma (N = 17, 59%), followed by cardiac (N = 10, 34%). Amniocentesis was performed in 20 cases and 10 were aneuploid. Only 10 fetuses (34%) were liveborn and only five (17%) survived the neonatal period. CONCLUSIONS: Antepartum diagnosis of NIHF conveys a grave perinatal prognosis. Associated anomalies can be expected in approximately 75% of cases. Even for those fetuses achieving viability, survival beyond the neonatal period is rare.

Fetal fibronectin and bacterial vaginosis are associated with preterm birth in women who are symptomatic for preterm labor.

OBJECTIVE: The purpose of this study was to codify the relationship between bacterial vaginosis/fetal fibronectin and preterm labor/birth. STUDY DESIGN: In this prospective study, 185 women who were symptomatic for preterm labor were assessed for bacterial vaginosis and fetal fibronectin. RESULTS: These women comprised 4 groups: group A (n=23 women; +bacterial vaginosis/+fetal fibronectin); group B (n=31 women; -bacterial vaginosis/+fetal fibronectin); group C (n=47 women; +bacterial vaginosis/-fetal fibronectin); and group D (n=84 women; -bacterial vaginosis/-fetal fibronectin). The time interval from gestational age at testing until delivery was significantly shorter for groups A and B versus groups C and D (P < or =.05 and P <.001, respectively). Similarly, delivery at <32 weeks of gestation was increased in group B (26%) compared with groups A (9%), C (2%), and D (5%; P <.009; odds ratio, 165.90; 95% CI, 30.02, 916.08). CONCLUSION: Women who are symptomatic for preterm labor should be considered for fetal fibronectin and bacterial vaginosis testing.

Diagnosis of postpartum infections: clinical criteria are better than laboratory parameter.

BACKGROUND: Physiologic increases in the leukocyte count and segmental neutrophil percentage during pregnancy alter the ability of these indices to predict infection. METHODS: Women with cesarean deliveries were assessed by leukocyte counts and segmented neutrophil percentage as well as clinical signs to detect postoperative infection. RESULTS: In 157 consecutive patients undergoing cesarean deliveries there was a significant physiologic increase between the preoperative and postoperative leukocyte count (12.4 +/- 3.9/uL vs. 14.8 +/- 3.4/uL, P < 0.001). The leukocyte count after delivery did not discriminate whether or not the patient would develop a postpartum infection or have significant hyperpyrexia. CONCLUSION: Due to physiologic changes associated with pregnancy, the leukocyte count and segmented neutrophil percentage do not predict infection. Therefore clinical findings are most important in diagnosing postpartum infections.