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Primary infertility associated with isolated cervical collecting diverticulum.

OBJECTIVE: To describe a previously unreported isolated congenital cervical diverticulum and its gynecologic, reproductive, and obstetrical implications. DESIGN: Case report. SETTING: A university hospital. PATIENT: A 31-year-old woman presenting with menometrorrhagia and primary infertility. Investigation revealed an isolated collecting cervical diverticulum causing prolonged postmenstrual spotting, possibly interfering with sperm capacitation and access to the uterine cavity. INTERVENTION(S): The examination included hysterosalpingography and magnetic resonance imaging. The combined hysteroscopy and laparoscopy revealed a 5 x 5 cm cervical diverticulum, around 1 cm from the external cervical os, leading to a short cervical canal connected to a normal uterine cavity. The patient achieved a pregnancy after controlled ovarian hyperstimulation and ultrasonographically guided intrauterine insemination. MAIN OTUCOME MEASURE(S): Pregnancy and obstetrical outcome. RESULT(S): Extensive evaluation revealed the patient's condition to be a previously undescribed congenital cervical anomaly. The patient's infertility was corrected by ovulation induction and sonographically guided intrauterine insemination, which resulted in a twin pregnancy. After 27 weeks of gestation, preterm labor complicated the delivery. CONCLUSION(S): The diagnosis and management of this unusual congenital cervical diverticulum present a particular challenge, as this congenital abnormality has not been previously described or reported.

Adult↗

Evaluation of early pregnancy by serial chorionic gonadotropin determinations: a comparison of methods by receiver operating characteristic curve analysis.

Two methods of evaluating early pregnancies by serial human chorionic gonadotropin (hCG) determinations were evaluated by receiver operating characteristic (ROC) curve analysis. The first method used normal values (mean and upper confidence limits) of the hCG doubling time (DT) determined by a linear regression analysis of hCG concentrations from 35 normal pregnancies during the first 42 postmenstrual days. In the second method, normal values were determined at multiple sampling ranges of hCG concentrations from 49 normal pregnancies. In the evaluation of 91 pregnancies of which 58 progressed to viability, 25 spontaneously aborted, and 8 were ectopic gestations, the ROC curves demonstrated that for any given false-positive rate, the use of multiple normal values of DT was more sensitive than the use of a single mean DT determined by linear regression analysis. The study indicates that a more precise definition of the normal values of the hCG-DT results in improved early detection of abnormal pregnancies.

Chorionic Gonadotropin↗

Pregnancy outcome after early amniotic fluid leakage after transabdominal multifetal reduction.

OBJECTIVE: To assess the importance of amniotic fluid leakage in the early period ( < 14 days) after the fetal reduction procedure. DESIGN: Prospective clinical study. SETTING: Pregnant women who underwent fetal reduction to twins in an academic, tertiary perinatal department. PATIENTS: Sixty triplet and 31 quadruplet pregnancies were identified before the ninth postmenstrual week of gestation. All patients underwent transabdominal multifetal pregnancy reduction was performed within 14 days of the procedure. INTERVENTIONS: Transabdominal multifetal pregnancy reduction from triplets and quadruplets to twins. MAIN OUTCOME MEASURE: Amniotic fluid leakage in the early period after fetal reduction. RESULTS: Early PROM occurred in eight (13.3%) patients from the triplets group and in six (19.3%) patients in the quadruplet group. Three of 60 (5.0%) patients from the triplet group and 1 of 31 (3.2%) patients from the quadruplet group miscarried before 24 weeks gestation. However, none of these patients had had PROM during the early period after the procedure. Early PROM did not influence the incidence of premature contractions of delivery and the reduction procedure, and 59% (99/169) of those who completed 24 gestational weeks delivered between 25 and 37 weeks. CONCLUSION: The presence of amniotic fluid leakage in the period close to the multifetal reduction procedure, although alarming, is not ominous for the remaining fetuses. We see no reason for any intervention in these patients.

Abortion, Spontaneous↗

Mechanism of gastroesophageal reflux in premature infants with chronic lung disease.

BACKGROUND/PURPOSE: The aim of this study was to characterize the motor events responsible for gastroesophageal reflux (GER) and esophageal acid clearance in a cohort of preterm infants with chronic lung disease (CLD). METHODS: Esophageal motility was recorded for 2 to 3 hours postprandially in 14 preterm infants with mild-moderate or moderate-severe CLD at 33 to 39 weeks postmenstrual age using a sleeve-side hole micromanometric assembly into which a pH probe had been installed. RESULTS: Twenty-six acid GER episodes were recorded by pH probe. Of these, 22 (85%) were associated with transient lower esophageal sphincter (LES) relaxation. Transient LES relaxations were significantly longer in duration than single swallows (13.7 seconds v 4.6 seconds, P < .001) and had lower nadir pressures (1.1 mm Hg v 2.5 mm Hg, P < .001). During periods of esophageal acidification (pH below 4), peristaltic esophageal body pressure wave sequences cleared acid refluxate more effectively than nonperistaltic pressure wave sequences. CONCLUSIONS: In preterm infants with CLD, transient LES relaxations are the predominant mechanism underlying GER, and esophageal clearance mechanisms are fully functional, which is similar to that seen in healthy preterm infants.

Chronic Disease↗

Esophageal body and upper esophageal sphincter motor responses to esophageal provocation during maturation in preterm newborns.

OBJECTIVES: We studied the maturation of esophageal body and upper esophageal sphincter (UES) motor responses that protect against reflux in newborns. STUDY DESIGN: The responses of esophageal body and UES on midesophageal provocation were quantified using a micromanometric water perfusion system and a specially designed catheter with a UES sleeve and 5 side-hole recording sites. Eighteen healthy premature infants were studied twice, at 33.4 weeks' and 35.7 weeks' mean postmenstrual ages (PMAs). RESULTS: Mean threshold volumes and the distribution of responses including secondary peristalsis, UES pressure increase, and primary peristalsis were similar for air and liquids. Secondary peristalsis and UES pressure increases were volume dependent for both studies, but their characteristics changed as PMA increased in that (1) completely propagated secondary peristalsis with liquids increased; (2) proximal esophageal contraction duration was shorter for air and liquids; and (3) propagating velocity for liquids was faster. CONCLUSIONS: Esophageal and UES motor responses to abrupt midesophageal provocation are present as early as 33 weeks' PMA, and the response-characteristics improve during development. Reflexes that may facilitate esophageal clearance include (1) secondary peristalsis; (2) esophago-UES-contractile reflex; and (3) esophago-deglutition response.

Deglutition Disorders↗

Growth, metabolic response, and development in very-low-birth-weight infants fed banked human milk or enriched formula. I. Neonatal findings.

Banked human milk has been widely used, although its composition and nutritional adequacy for preterm infants are uncertain. We randomized 76 healthy infants of less than or equal to 1500 gm birth weight to ad lib feedings of frozen BHM or a protein-mineral-calorie-enriched formula (Similac Special Care) designed to sustain intrauterine accretion rates; BHM contained 2.2 gm fat/100 ml and 60 kcal/100 ml (gross energy). Infants fed BHM ingested more milk (197 vs 165 ml/kg/day) but less gross energy (118 vs 143 kcal/kg/day); grew less rapidly in weight (15 vs 30 gm/day), length (0.7 vs 1.1 cm/wk), and head circumference (0.8 vs 1.2 cm/wk); and were discharged at a lower weight (2200 vs 2348 gm) and older age (61 vs 47 day) than infants fed formula (P less than 0.02). At 37 weeks' postmenstrual age, infants fed BHM were less responsive to Brazelton inanimate stimuli (mean total score 5.0 vs 7.5; P less than 0.02). With few exceptions, blood amino acids, pH, and serum electrolyte values were similar in both groups. The different caloric intake of our feeding groups may explain only part of the large difference in growth rate. Donor milk should not be fed to preterm infants unless it has been analyzed and the feedings shown to provide a nutrient intake considered appropriate to the needs of these infants.

Body Weight↗

Randomized clinical trial of an oscillating air mattress in preterm infants: effect on apnea, growth, and development.

To investigate claims that oscillating mattresses reduce apnea of prematurity and improve growth and neurobehavioural development, we performed a randomized clinical trial using a predetermined sample size. Preterm infants weighing from 750 to 1750 gm at birth were randomly assigned, by 250 gm strata, to either a conventional mattress (n = 63) or to an air mattress (n = 59) oscillating at 14 to 16 regular pulses per minute. Infants remained on the oscillating air mattress for at least 7 days or until 34 weeks postmenstrual age. Apneic episodes occurred and required treatment equally in the two groups; this lack of an effect was seen for both sexes and all weight groups. Both weight and energy intake were similar. Neurobehavioral development as shown by sleep state, habituation testing, and behavioral assessment at term, 3, 6, and 12 months was similar in the two groups. There was no difference in the incidence of neurologic abnormalities. We conclude that an oscillating air mattress has no prophylactic value in reducing apnea and does not enhance growth and development.

Air↗

Circadian variations of urinary electrolyte concentrations in preterm and term infants.

OBJECTIVES: To determine whether a circadian variation of urinary excretion of calcium and phosphorus exists in preterm infants. STUDY DESIGN: We studied 70 newborn infants (median birth weight 1920 gm, range 660 to 3550 gm; median gestational age 34 weeks, range 25 to 42 weeks) at a median postmenstrual age of 36 weeks (range 32 to 42 weeks). Within a period of 24 hours, four urine specimens were collected during 6-hour periods. The concentrations of calcium, phosphorus, sodium, potassium, and creatinine were determined and creatinine quotients were calculated for each specimen. RESULTS: No clinically relevant circadian variation in urinary excretion for any of these minerals was found. CONCLUSION: If spot urine specimens are used to monitor calcium and phosphorus balance in preterm infants, the time of the day these are collected is not important.

Circadian Rhythm↗

Oral feeding in low birth weight infants.

To gain a better understanding of the development of sucking behavior in low birth weight infants, the aims of this study were as follows: (1) to assess these infants' oral feeding performance when milk delivery was unrestricted, as routinely administered in nurseries, versus restricted when milk flow occurred only when the infant was sucking; (2) to determine whether the term sucking pattern of suction/ expression was necessary for feeding success; and (3) to identify clinical indicators of successful oral feeding. Infants (26 to 29 weeks of gestation) were evaluated at their first oral feeding and on achieving independent oral feeding. Bottle nipples were adapted to monitor suction and expression. To assess performance during a feeding, proficiency (percent volume transferred during the first 5 minutes of a feeding/total volume ordered), efficiency (volume transferred per unit time), and overall transfer (percent volume transferred) were calculated. Restricted milk flow enhanced all three parameters. Successful oral feeding did not require the term sucking pattern. Infants who demonstrated both a proficiency > or = 30% and efficiency > or = 1.5 ml/min at their first oral feeding were successful with that feeding and attained independent oral feeding at a significantly earlier postmenstrual age than their counterparts with lower proficiency, efficiency, or both. Thus a restricted milk flow facilitates oral feeding in infants younger than 30 weeks of gestation, the term sucking pattern is not necessary for successful oral feeding, and proficiency and efficiency together may be used as reliable indicators of early attainment of independent oral feeding in low birth weight infants.

Bottle Feeding↗

Comparison between observation of spontaneous movements and neurologic examination in preterm infants.

OBJECTIVE: The Prechtl method of qualitative assessment of general movements (GMs) has been shown to be a good predictor of neurologic outcome in fetuses, preterm infants, and term infants. The aim of this study was to compare the results of this new technique with those of traditional neurologic examination and of cranial ultrasonography in preterm infants. METHODS: Serial videotape recordings (with off-line assessment of GMs), ultrasound examination of the brain, and neurologic examinations were performed from birth until about 6 months of corrected age, on a group of 66 preterm infants whose gestational age ranged from 26 to 36 weeks (mean 30.7 weeks). The agreement between the two techniques and their predictive power, with respect to the neurologic outcome at 2 years of corrected age, were evaluated for five different age groups from preterm age to 65 weeks of postmenstrual age. RESULTS: Overall agreement of the neurologic and GM findings was 80.3% and strongly age related (lower during the preterm and term periods and higher thereafter). At all ages the results of GM observation correlated highly with neurologic outcome; they showed higher sensitivity and specificity than the neurologic examination. This held true in particular before term age, when poor neurologic responses might be related to transient complications, and at term age, mainly because of infants with normal neurologic examination results but unfavorable outcome. During the preterm period the ultrasound results showed a better specificity and a lower sensitivity to outcome than GM findings. CONCLUSIONS: The results of this study indicate that quality assessment of GMs should be added to traditional neurologic assessment, neuroimaging, and other tests of preterm infants for diagnostic and prognostic purposes.

Child Development↗

Growth and body composition in infants with bronchopulmonary dysplasia up to 3 months corrected age: a randomized trial of a high-energy nutrient-enriched formula fed after hospital discharge.

OBJECTIVES: (1) To determine whether nutrient malabsorption or inadequate nutrient intake were involved in the cause of growth delay in patients with bronchopulmonary dysplasia, and (2) to determine whether a nutrient-enriched formula given to infants with bronchopulmonary dysplasia to 3 months corrected age improves the rate of growth with greater lean and bone mass accretion when compared with infants fed an isoenergetic standard infant formula. STUDY DESIGN: A blinded, nutrition intervention trial of 60 preterm infants with bronchopulmonary dysplasia (birth weight, 866 +/- 169 g, gestational age, 26 +/- 1.5 weeks) randomized to either nutrient-enriched formula or standard formula. Growth, body composition, and nutrient retention were compared between groups by Student's t tests and analysis of covariance. RESULTS: Infants fed the enriched formula had significantly greater nitrogen and mineral retention at 38 weeks' postmenstrual age, and only the infants fed enriched formula had zinc retention similar to the intrauterine accretion. At 3 months corrected age infants fed enriched formula attained greater length (P < .05), greater radial bone mineral content (P < .01), and greater lean mass (P < .01). The male infants in the enriched formula group had greater whole body bone mineral content than did male infants in the standard formula group (P = .02). CONCLUSIONS: Greater linear growth and lean and bone mass in the enriched formula group suggests that infants with bronchopulmonary dysplasia attain faster "catch-up" growth when fed higher intakes of protein, calcium, phosphorus, and zinc than provided in standard proprietary formulas.

Analysis of Variance↗

Motor nerve conduction velocity in very preterm infants in relation to L-thyroxine supplementation.

BACKGROUND: Transient hypothyroxinemia is common in preterm infants and has been associated with neurodevelopmental dysfunction and slow nerve conduction velocity. It is still unknown whether L-thyroxine supplementation is required. During an L-thyroxine supplementation trial, motor nerve conduction velocity was measured to answer the question whether L-thyroxine supplementation improves motor nerve conduction velocity. METHODS: Two hundred infants < 30 weeks' gestational age were enrolled in a randomized, double-blind, placebo-controlled L-thyroxine supplementation trial. L-Thyroxine (8 micrograms/kg birthweight per day) or a placebo was administered during the first 6 weeks of life. Motor nerve conduction velocity was measured in the ulnar and posterior tibial nerve shortly after birth, at 2 weeks, at 40 weeks, and at 66 weeks postmenstrual age. RESULTS: At 2 weeks, the ulnar motor nerve conduction velocity had improved in the L-thyroxine group compared with the placebo group, although the difference was not statistically significant (difference between means: 0.8 msec; 95% CI: -0.13 to 1.80; p = 0.06). Later on, no effect of L-thyroxine supplementation on motor nerve conduction velocity was found. CONCLUSION: This study shows that in infants < 30 weeks' gestational age L-thyroxine supplementation during the first 6 weeks of life does not clearly improve motor nerve conduction velocity.

Double-Blind Method↗

Characterization of esophageal body and lower esophageal sphincter motor function in the very premature neonate.

OBJECTIVES: To characterize esophageal body and lower esophageal sphincter (LES) motor function in very premature infants. STUDY DESIGN: Esophageal manometry was performed in 12 very premature infants of 26 to 33 weeks' postmenstrual age (PMA) (body weights of 610-1360 g). Esophageal motor patterns were recorded for 30 minutes with a perfused micromanometric sleeve assembly (outer diameter, 2.0 mm). RESULTS: Esophageal pressure waves triggered by dry swallows were predominantly (84%) peristaltic in propagation sequence. All infants showed tonic LES contraction; the mean resting LES pressure (LESP) for individual infants ranged from 5.0 +/- 4.1 mm Hg to 20.0 +/- 4.8 mm Hg. In all infants the LES relaxed (duration, 5.8 +/- 3.0 seconds; nadir pressure, 1.8 +/- 2.6 mm Hg) in response to pharyngeal swallows. Transient LES relaxations (TLESRs) (duration, 21.7 +/- 8.7 seconds; nadir pressure, 0.1 +/- 1.8 mm Hg) occurred on average 2.6 +/- 1.6 times per study; 86% of these relaxations triggered esophageal body common cavity events known to be associated with gastroesophageal reflux. CONCLUSIONS: Esophageal motor function is well developed in very premature infants. Our data also suggest that TLESR is the predominant mechanism of reflux in these babies.

Esophagogastric Junction↗

Randomized comparison of high-frequency ventilation with high-rate intermittent positive pressure ventilation in preterm infants with respiratory failure.

OBJECTIVE: In a randomized, controlled, multicenter trial, we tested the hypothesis that high-frequency ventilation (HFV) with a high lung volume strategy results in fewer treatment failures than intermittent positive pressure ventilation (IPPV) with high rates and low peak inspiratory pressures. STUDY DESIGN: Infants with a gestational age between >/=24 weeks and <30 weeks, requiring mechanical ventilation within 6 hours of birth, were randomly assigned to receive either IPPV or HFV until 240 hours after randomization, extubation, or meeting treatment failure criteria. Treatment failure, the primary end point, was determined when air leaks, an oxygenation index >35 to 45 (depending on gestational age), death, or chronic lung disease occurred. Chronic lung disease was defined as persistent requirement of mechanical ventilation, continuous positive airway pressure, or supplemental oxygen at a postmenstrual age of 36 weeks. Secondary end points included the incidence of intracranial hemorrhage. RESULTS: The third scheduled interim analysis led to termination of the trial after recruitment of 284 infants. Treatment failure criteria were met by 46% of infants receiving IPPV and 54% of infants receiving HFV (1-tailed primary hypothesis, P =.92; 2-tailed chi2 test, P =.15). Air leaks occurred in 31% and 42% (P =.042), CLD in 23% and 25%, and grade 3-4 intracranial hemorrhage in 13% and 14% of IPPV-treated and HFV-treated patients, respectively. The mortality rate before discharge was 10% in both groups. CONCLUSION: HFV with a high lung volume strategy did not cause less lung injury in preterm infants than IPPV with a high rate and low peak inspiratory pressures.

Bronchopulmonary Dysplasia↗

The voiding pattern of healthy preterm neonates.

PURPOSE: To elucidate further the maturation of voiding habits from gestation to infancy we investigated the free voiding pattern of healthy preterm neonates. MATERIALS AND METHODS: We evaluated 11 male and 8 female healthy preterm newborns at a mean of 32 weeks after cessation of menstrual flow (postmenstrual age). Assessment was done in the neonatal ward using 4-hour voiding observation, a method described previously in studies of free voiding pattern of full-term newborns. RESULTS: The voiding pattern of male and female preterm neonates was characterized by 1 void per hour and a mean voided volume of 53% of bladder capacity with 58% frequency of interrupted voiding. Residual urine was increased but varied during observation (mean 11% bladder capacity) and was 0 after at least 1 void during 4 hours in 14 of the 19 subjects. Two-thirds of all voiding occurred during sleep, whereas a third of the newborns showed signs of arousal with a mean awake time of only 17 minutes. CONCLUSIONS: The voiding pattern of preterm versus full-term subjects is characterized by an increased number of interrupted voidings, further indicating that these voidings represent immature behavior of detrusor-sphincter coordination. Also, the high number of voidings during sleep suggest a more immature pattern for preterm newborns.

Female↗

Venlafaxine in the treatment of premenstrual dysphoric disorder.

OBJECTIVE: To evaluate the efficacy and safety of venlafaxine, a new-generation antidepressant that selectively inhibits serotonin and norepinephrine reuptake, in the treatment of premenstrual dysphoric disorder (PMDD). METHOD: We conducted a randomized, double-blind, placebo-controlled, parallel-group, flexible-dose trial. After three screening cycles, including a single-blind placebo cycle, 164 women were randomly assigned to double-blind treatment with venlafaxine (50-200 mg/day) or placebo for four menstrual cycles. Primary outcome measures were the total premenstrual symptom scores as assessed by a daily symptom report (DSR) and the Hamilton Rating Scale for Depression. RESULTS: Venlafaxine was significantly more effective than placebo in reducing PMDD symptoms as assessed by DSR scores (P <.001 for last observation carried forward and observed analyses). Sixty percent of venlafaxine versus 35% of placebo subjects improved >50% (P =.003). Forty-three percent of venlafaxine subjects versus 25% of placebo subjects experienced symptom remission, defined as reduction of DSR scores to the postmenstrual level (P =.034). Venlafaxine treatment was significantly better than placebo for all statistically derived DSR factors (mood, function, pain, and physical symptoms). Improvement was relatively swift, with approximately 80% symptom reduction in the first treatment cycle. Mean venlafaxine doses ranged from 50 mg/day in the first treatment cycle to 130 mg/day in the fourth treatment cycle. Adverse events such as nausea, insomnia, and dizziness were mild and transient. CONCLUSIONS: Venlafaxine is significantly more efficacious than placebo for PMDD treatment. Response to treatment can occur in the first treatment cycle, and venlafaxine is well tolerated. Further studies are needed to evaluate the potential of intermittent (luteal phase) dosing for this cyclic disorder and the efficacy of long-term maintenance treatment with venlafaxine.

Adult↗

Measurement of volume of cerebral blood flow in healthy preterm and term neonates with ultrasound.

Changes in cerebral blood flow are important in the pathogenesis of ischaemic brain damage, but standard methods cannot measure volume of cerebral blood flow quantitatively in neonates. We used colour duplex sonography of the extracranial cerebral arteries to measure volume of global cerebral blood flow in 67 healthy preterm and term neonates. Volume of cerebral blood flow increased between the postmenstrual ages of 34 weeks (median 33 mL/min [range 23-43]) and 42 weeks (85 mL/min [57-104]). However, intersession and interobserver variability was quite large. This non-invasive method will allow quantitative bedside monitoring of global brain perfusion in preterm and term neonates with pathological disorders, and could also be used to monitor effects of neuroprotective measures.

Blood Flow Velocity↗

Effect of oral contraceptives on platelet noradrenaline and5-hydroxytryptamine receptors and aggregation.

Characteristics of receptor sites on platelets for noradrenaline (NA) and serotonin (5-HT) changed significantly between day 21 and day 28 of treatment in healthy women taking oral contraceptives. NA-induced and 5-HT-induced platelet aggregation and 5-HT uptake vaired accordingly. In untreated women with normal cycles no changes in either receptor site or in platelet function occurred between the luteal and postmenstrual phases. It is concluded that the observed changes are due to a pharmacological effect of the oral contraceptive rather than a normal physiological variation.

Adult↗