First-trimester hyperglycosylated human chorionic gonadotropin and development of hypertension.

OBJECTIVE: This study aimed to determine whether urine levels of hyperglycosylated human chorionic gonadotropin (HhCG) in the first trimester are predictive of subsequent development of hypertension during pregnancy METHOD: This prospective cohort study consisted of women seeking care before 12 weeks gestation. A clean catch urine was obtained at the first prenatal visit and tested for HhCG and creatinine levels. The median HhCG levels and multiples of the median (MoM) by gestational age were compared between the groups that either developed hypertension or did not. RESULTS: Urine HhCG were determined for 204 women between 4 weeks 4 days to 11 weeks 6 days. The median HhCG of those who developed gestational hypertension (n = 7) or preeclampsia (n = 15) did not differ from the group that did not (median: 284 ng/mg creatinine vs 365 ng/mg; p = 0.55). If the MoM of HhCG for the no hypertension group was 1.00, the MoM of HhCG for the hypertension group was 0.93 (p = 0.93). A possible association was observed after 10 weeks between low HhCG levels and the development of late-onset hypertension (≥34 weeks). CONCLUSIONS: Prenatal screening for subsequent hypertension is unreliable with a single measurement of maternal urine HhCG at 10 weeks or less.

Envenomations during pregnancy reported to the national poison data system, 2009-2018.

Envenomations during pregnancy have consequences affecting both maternal and fetal outcomes. U.S. poison center data on envenomations offers a comparative view of envenomations in pregnant and non-pregnant women. The National Poison Data System of the American Association of Poison Control Centers was searched for cases of envenomation during pregnancy between January 1, 2009 and December 31, 2018 and compared with exposures to non-pregnant females of childbearing age. Odds ratios and descriptive statistics were used where appropriate. There were a total of 3,555 venomous animal exposures in pregnant women during this 10-year period, most commonly with scorpion stings. These were compared with 87,553 envenomations in non-pregnant women of childbearing age during that time period. Overall, drug treatment was administered in 350 (9.9%) cases of envenomation in pregnant women compared with 21,381 (24.4%) of non-pregnant patients. Antihistamines were less likely to be used in pregnant patients with scorpion (1.8% v. 9.2%), hymenoptera (bee, wasp, or hornet) (12.4% v. 37.1%), black widow spider (2.8% v. 8.1%), and caterpillar (10.4% v. 37.7%) exposures. There was an increased likelihood of antivenom use during pregnancy with rattlesnake envenomations (85.0% v. 58.9%) and black widow spider bites (4.8% v. 2.2%). There were no maternal deaths, and most maternal outcomes were coded as having no (1.0%) or minor (87.6%) effects. Three fetal deaths occurred, all following snakebites and all before 20 weeks gestation. Two were attributed as related, and one as of uncertain relationship to the exposure, by the managing poison centers. Most envenomations caused no or minor effects to pregnant women.

In utero drug therapy.

Drug therapy directed toward the fetus would be intended for either treating a fetal disorder or improving the capacity for later intrauterine or postnatal adaptation. Most reported trials involve single cases or small numbers of fetuses receiving the drug transplacentally after the first trimester, but before attaining maturity. Studies usually involve a single drug administered shortly before delivery. Treatments that are more direct or begun earlier in gestation are being attempted, but our limited understanding of fetal pharmacokinetics forces us to proceed cautiously. Studies to date have shown no risks to the mother and newborn infant, but long-term follow-up is necessary.

A physician's prerogative to prescribe drugs for off-label uses during pregnancy.

Physicians frequently prescribe drugs for indications other than those on the product label. Reasons for such off-label use during pregnancy include: prevention of repetitive abortion, inhibition of premature labor, reduction of fetal or neonatal infection, reduction in development of preeclampsia and its complications, and ripening of the cervix or induction of labor. A physician has a legal right to prescribe for off-label indications despite regulatory, manufacturer, and cost constraints. Such prescribing habits would not be considered experimental if based on sound scientific evidence. Adequate and well-controlled studies are difficult to perform during pregnancy. Evidence of widespread use and support from another qualified clinician are methods of justifying off-label prescribing. Each patient is entitled to know why she and her fetus would benefit from the treatment and whether any unnecessary risk is anticipated. Legible documentation of these discussions in the medical records is important.

Patient-controlled analgesia in obstetrics and gynecology.

Patient-controlled analgesia, which provides pain relief through self-administration of intravenous doses of opioids, is widely available and advocated as an effective analgesic modality. This report reviews published experiences with patient-controlled analgesia during labor and after cesarean delivery or major gynecologic surgery. Currently employed devices allow accurate record-keeping of drug use and permit patient mobility. No one device has been shown to be preferable. The form of administration most commonly described is infusion of morphine or meperidine on demand without combined continuous basal infusion. During labor, brief but progressively intensifying episodes of pain undermine the effectiveness of these devices when used intravenously. Compared with intramuscular administration of narcotics, patient-controlled analgesia after cesarean or major gynecologic surgery has been judged by patients to be more acceptable in achieving a balance between tolerable pain and sedation. Respiratory depression has been rare and is often attributable to misprogramming. Costs of these devices can be justified with frequent usage and are at least partially offset by more efficient use of nursing personnel for pain management.

Maternal perception of fetal movement and perinatal outcome.

The maternal perception of fetal activity was studied in 306 clinic patients who counted for 2 predetermined hours each day. "Alarming" and "reassuring" fetal movement patterns were defined from statistical analysis. All reassuring fetal movement patterns were followed by reactive nonstress tests (NSTs), and the 2 nonreactive NSTs were preceded by alarming fetal activity. No relationship between urinary estriol determinations and prior fetal activity was present. Excluding congenital anomalies, perinatal distress was infrequent with prior reassuring fetal activity and arose primarily from intrapartum factors. An alarming fetal movement pattern was twice as frequent in high-risk pregnancies and was associated with a significantly greater risk of subsequent perinatal distress (P less than .0001). Clinical applications of the proposed technique are discussed.

Umbilical cord length and intrapartum complications.

The length of umbilical cords was studied in 536 term deliveries to test the hypothesis that a short or long umbilical cord is more frequently associated with certain intrapartum complications. The mean umbilical cord length was 55 cm (range, 14 to 129 cm). A short cord was defined as 35 cm or less (lower sixth percentile). Umbilical cord accidents were most frequent in the presence of a long cord (20 of 32 cases, 62%). Inadequate fetal descent was significantly more common when a long cord or an excessively short cord (25 cm or less, lower first percentile) was found. Fetal heart rate (FHR) abnormalities that primarily reflected cord compression patterns were significantly more frequent in the presence of a short (17 of 27 cases, 63%) or a long cord (28 of 32 cases, 87%), as compared with a normal length cord (145 of 393 cases, 37%). The measurement of umbilical cord length requires minimal effort, no expense, and may explain certain intrapartum FHR abnormalities or an arrest of fetal descent.

Conditions affecting nonstress test results.

A prospective investigation was conducted to examine associations between selected conditions encountered during nonstress testing with the intent of explaining false nonreactive results. During a 16-month period, nonstress tests (NSTs) were performed in 315 pregnancies; 64 (12%) of the initial 534 satisfactory tests had nonreactive patterns. Approximately one third (22 of 64, 34%) of these nonreactive tests either remained nonreactive or were followed by a positive or suspicious contraction stress test that same day. When compared with pregnancies that gave reactive test results, a nonreactive pattern was not found to be more commonly associated with maternal obesity, fasting, certain prescribed medications (methyldopa, phenobarbital, insulin), time of day, or recent amniocentesis. Recent cigarette smoking was infrequent (108 tests, 20%) but might explain a falsely nonreactive result. The data suggests that NST results might instead have been influenced by fetal activity and fetal health during the test period.

Multiple gestation: time interval between delivery of the first and second twins.

A clinical investigation was undertaken to challenge the commonly accepted view that the interval between the birth of the first and second twins should be preferably within 15 minutes and certainly no more than 30 minutes. During 1981 and 1982, 115 patients with live-born twins at 34 or more weeks' gestation underwent an attempted vaginal delivery at four regional perinatal centers. The interval between vaginal delivery of the first and second twins (mean, 21 minutes, range, one to 134 minutes) was 15 minutes or less in 70 (61%) cases and more than 15 minutes in 45 (39%) cases. Excluding conditions associated primarily with prematurity, all second twins delivered beyond 15 minutes did well despite the delay and had no signs of excess trauma or low five-minute Apgar scores. Maternal complications were also uncommon, although combined vaginal-abdominal delivery was more frequent if there was a delay of more than 15 minutes (eight of 45 versus two of 70, P less than .02). The authors conclude that if there is continuous fetal and uterine monitoring, a time restriction for the delivery interval between the first and second infants is not necessary.

Patient-controlled analgesia for post-cesarean section pain.

Recent reports have suggested that patient-controlled analgesia is an effective means of narcotic administration in postoperative patients. This prospective investigation was undertaken to determine the efficacy and safety of patient-controlled anesthesia infusion after cesarean section. During a recent ten-month period, 130 patients were assigned randomly to receive meperidine by pump or intramuscular injection. Meperidine consumption using the device varied widely to meet individual needs. Overdosage and drug dependence were not encountered with the prescribed drug concentrations. The patient-controlled analgesia method provided less sedation and more immediate pain relief without the need for painful injections. The additional cost of renting the infuser device was offset by combined patient and nursing satisfaction. We conclude that patient-controlled infusion of meperidine is safe and effective in satisfying individual patient needs after cesarean section.

Relation of mild idiopathic polyhydramnios to perinatal outcome.

The relation between clinically obvious polyhydramnios and poor perinatal outcome has been described. Much less is known about mild, unexplained polyhydramnios, which usually is initially suggested by sonographic examination late in gestation. The purpose of the present investigation was to relate mild idiopathic polyhydramnios to perinatal outcome. Mild polyhydramnios was defined sonographically as an amniotic fluid index of 24.1-39.9 during fetal biophysical testing. All subjects had singleton gestations not complicated by conditions known to predispose to polyhydramnios. We diagnosed mild polyhydramnios in 97 of 1177 patients (8.2%) undergoing fetal testing at 26-42 gestational weeks. Premature delivery, intrapartum complications, and neonatal depression were no more frequent in the pregnancies complicated by mild, unexplained polyhydramnios than in a comparable control group with normal fluid volume. The mild polyhydramnios group showed a significantly higher incidence of birth weight greater than 4000 g than did the control group (18.6 versus 8.6%; P less than .05). We conclude that mild idiopathic polyhydramnios in late gestation is relatively common. Except for a higher incidence of large for gestational age fetuses, this condition by itself is not associated with an increased risk of adverse perinatal outcomes.

Double-blind, placebo-controlled study of ranitidine for gastroesophageal reflux symptoms during pregnancy.

OBJECTIVE: To determine whether ranitidine (Zantac) taken once or twice daily is effective for relieving symptoms of gastroesophageal reflux among pregnant women who had failed conservative measures. METHODS: Volunteers with heartburn despite antacids were sought among our obstetrics clinic population for this double-blind, placebo-controlled, triple crossover trial. After a baseline week, 20 patients were randomized to receive the three following weekly regimens: ranitidine 150 mg twice daily, placebo in the morning and ranitidine 150 mg in the evening, or placebo twice daily. Daily scores on symptom diaries, global assessments, and number of antacids taken were compared among the 18 patients completing the study. RESULTS: The twice-daily dosage of ranitidine was the only regimen found to reduce heartburn symptoms when compared with the baseline (P < .001) or a placebo (P < .01). Compared with ranitidine taken once daily, the twice-daily dosing prompted less need for antacid tablets compared with the placebo (P < .05 versus P > .05) and to the baseline (P < .001 versus P < .05). The average reduction of heartburn severity using twice-daily ranitidine was 55.6% when compared with baseline (95% confidence interval [CI] 34.8%, 76.5%) was 44.2% when compared with placebo (95% CI 15.4%, 72.9%). CONCLUSION: This study indicates the efficacy of ranitidine 150 mg taken twice daily, rather than once daily, for relief of gastroesophageal reflux symptoms during pregnancy.

Obstetric care and intraventricular hemorrhage in the low birth weight infant.

A concern of the obstetrician is whether any single event or combination of events before delivery places a prematurely born infant at increased risk of developing periventricular-intraventricular hemorrhage, a form of intracranial hemorrhage in 40 to 45% of all low birth weight infants. In this three-year retrospective study, 103 infants weighing less than 1500 g and delivering on or before the 35th gestational week showed evidence of intraventricular hemorrhage by routine cranial ultrasound scan. The finding of maternal hypertension, vaginal bleeding, or preterm ruptured membranes was similar in infants with intraventricular hemorrhage and a matched group of infants without hemorrhage. Premature labor, breech presentation, mode of delivery, and outborn birth also were not significantly different between the two groups. The finding of intraventricular hemorrhage in the low birth weight infant is related less to any one or combination of two prior obstetric events than to extreme prematurity and accompanying neonatal complications.

Weekly administration of prostaglandin E2 gel compared with expectant management in women with previous cesareans. Prepidil Gel Study Group.

OBJECTIVE: To compare the clinical effectiveness and safety of outpatient administration of intracervical prostaglandin (PG) E2 gel with expectant treatment for women desiring vaginal births after cesareans. METHODS: This was a randomized, multicenter investigation involving term pregnant women who each had one previous low-transverse cesarean and an unfavorable cervix (Bishop score no more than 6), and who was a candidate for vaginal delivery. They were assigned to receive 0.5 mg of PGE2, (Prepidil; Pharmacia-Upjohn, Kalamazoo, MI) intracervically at 39 weeks' gestation, repeated at weekly office visits for up to three doses, or expectant treatment. The main outcome variable was vaginal birth. RESULTS: Of 294 cases, 143 received gel and 151 were treated expectantly. No differences between groups were found for maternal age, race, or Bishop score. Compared with the expectant treatment group, the PGE2 gel group was not more likely to deliver sooner or vaginally (57% versus 55%, P = .68). The onset of labor, duration of labor among those delivering vaginally, and 1- and 5-minute Apgar scores were not different between groups. No uterine ruptures occurred, and adverse effects were equally likely in both groups. CONCLUSION: Although its safety was confirmed for outpatient use, weekly doses of intracervical PGE2 did not improve the likelihood of vaginal births after cesareans.

Antepartum prediction of the postmature infant.

A prospective investigation was undertaken to determine whether present antepartum methods of fetal assessment were useful in predicting postmaturity. Thirty-two (22%) of 147 strictly defined postdate pregnancies produced infants with signs of postmaturity. Clinical findings, fetal heart rate testing (primarily nonstress tests), and fetal movement charting were not found to be reliable predictors. Single-voiding estrogen:creatinine (E:C) ratios were significantly (P less than .0001) lower in fetuses with subsequent findings of postmaturity than in those without such signs, and all subnormal values were associated with postmature infants. Twenty-four of 29 pregnancies with oligohydramnios diagnosed by ultrasonography produced postmature infants, whereas 110 of 118 pregnancies with either pockets or an adequate volume of amniotic fluid produced infants who were not postmature. Of the fetal surveillance methods used in the authors' clinic, subnormal E:C ratios and ultrasonic evidence of oligohydramnios were the most reliable predictors of postmaturity.

Effect of a single dose of oral pseudoephedrine on uterine and fetal Doppler blood flow.

Pseudoephedrine, a stereoisomer of ephedrine with alpha- and beta-adrenergic properties, is the active ingredient in over-the-counter oral decongestants. Its safety during pregnancy has not been studied adequately. The purpose of this investigation was to evaluate the effects of pseudoephedrine on uterine and fetal Doppler blood flows. Twelve healthy pregnant women between 26-40 weeks' gestation ingested a standard 60-mg dose of pseudoephedrine. A pulsed Doppler system was used to perform blood flow measurements of the uterine arcuate artery, fetal aorta, and umbilical artery before dosing, immediately thereafter, and at 15-minute intervals during the first 3 hours after drug ingestion. Blood flow velocities were not altered significantly after dosing in either the maternal or fetal circulation. In no case did absolute fetal or uterine blood flow velocities decrease significantly or systolic/diastolic ratios persistently elevate to abnormal values. We conclude that no significant alterations in the uterine or fetal circulations occur after the ingestion of a single dose of oral pseudoephedrine by healthy pregnant patients in the third trimester.

Uterine and fetal Doppler flow changes from a single dose of a long-acting intranasal decongestant.

Oxymetazoline, an alpha-adrenergic agent, is the active vasoconstrictor in long-acting intranasal decongestants. This investigation studied the effects of oxymetazoline on the maternal and fetal circulations. Twelve healthy gravid patients in the third trimester (27-39 weeks) underwent flow velocity measurements by the same sonographer using a pulsed Doppler system (ATL Ultramark 4 machine). Maternal and fetal indices were recorded 15 minutes before dosing, immediately thereafter, and at 15-minute intervals during the first 2 hours after the drug was given. No significant changes were found in either the maternal blood pressures or pulse rates. Blood flow velocities did not change significantly from baseline for the uterine arcuate artery, fetal aorta, or umbilical artery circulations. In no case did absolute blood flow velocity decrease significantly or systolic/diastolic ratios elevate to worrisome values. For uncomplicated pregnancies, we conclude there are no significant acute changes in the maternal and fetal circulations after a single dose of intranasal oxymetazoline.

Randomized comparison of meperidine and fentanyl during labor.

This randomized investigation compared the efficacy of the conventional narcotic, meperidine, and a more potent and short-acting analgesic, fentanyl, during labor. One hundred five women with uncomplicated term pregnancies in active labor were randomly assigned to receive either intravenous fentanyl (50-100 micrograms every hour) or meperidine (25-50 mg every 2-3 hours) in a non-blinded manner. The analgesics were rated equivalent in efficacy. Maternal nausea, vomiting, and prolonged sedation occurred more frequently in the meperidine group. Naloxone use was significantly less in fentanyl- than in meperidine-exposed infants (one of 49 versus seven of 56; P less than .05). Neuroadaptive testing at approximately 2 hours and 24 hours postnatally revealed similar averaged scores in the two groups. Using the described intravenous dosing schedule, fentanyl was preferable to meperidine during labor because there was no prolonged maternal sedation or vomiting necessitating therapy and the requirement for neonatal naloxone was reduced.

An intravaginal controlled-release prostaglandin E2 pessary for cervical ripening and initiation of labor at term.

The purpose of this randomized, double-blind study was to evaluate the efficacy and safety of a new controlled-release hydrogel pessary for ripening the cervix and initiating labor. Subjects had an entry Bishop score of 4 or less and gestational age of 37 or more weeks. One hundred fourteen women received a placebo pessary and 101 received the hydrogel pessary, containing 10 mg of prostaglandin (PG) E2. Compared with the placebo group, those given the PGE2 pessary were more likely to have an increase in Bishop score of 3 or more (60 or 59% versus 21 or 18%; P less than .0001), change to a Bishop score of 6 or higher (59 or 58% versus 18 or 16%; P less than .0001), and active labor (68 or 67% versus 15 or 13%; P less than .0001). Including the crossover study, uterine hyperstimulation (28 of 182, 15%) and fetal heart rate abnormalities (18 of 182, 10%) in PGE2-treated subjects were reversed on removal of the pessary with no apparent harm to the mother or fetus. These temporary adverse effects appeared while the pessary was in place and after the onset of active labor. Oxytocin was unnecessary in 89 of 182 (49%) of the PGE2-treated cases and was used more often to augment than to induce labor. We conclude that the described controlled-release PGE2 vaginal pessary induces appreciable cervical ripening and frequently initiates active labor with little or no need for oxytocin. The pessary may cause uterine hyperstimulation or fetal heart rate abnormalities, but these would be expected to reverse on removal of the pessary.