Maternal pregnancy-specific anxiety is associated with child executive function at 6-9 years age.

Because fetal brain development proceeds at an extremely rapid pace, early life experiences have the potential to alter the trajectory of neurodevelopment, which may increase susceptibility for developmental and neuropsychiatric disorders. There is evidence that prenatal maternal stress and anxiety, especially worries specifically related to being pregnant, influence neurodevelopmental outcomes. In the current prospective longitudinal study, we included 89 women for whom serial data were available for pregnancy-specific anxiety, state anxiety, and depression at 15, 19, 25, 31, and 37 weeks gestation. When the offspring from the target pregnancy were between 6 and 9 years of age, their executive function was assessed. High levels of mean maternal pregnancy-specific anxiety over the course of gestation were associated with lower inhibitory control in girls only and lower visuospatial working memory performance in boys and girls. Higher-state anxiety and depression also were associated with lower visuospatial working memory performance. However, neither state anxiety nor depression explained any additional variance after accounting for pregnancy-specific anxiety. The findings contribute to the literature supporting an association between pregnancy-specific anxiety and cognitive development and extend our knowledge about the persistence of this effect until middle childhood.

Effect of intraamniotic fluid thyroxine injection on fetal serum and amniotic fluid iodothyronine concentrations.

Seven hundred micrograms of T4 were injected into the amniotic cavity 24 h before delivery of five pregnant women scheduled for elective cesarean section at term. T4, T3, and rT3 concentrations were measured by RIA in amniotic fluid obtained at the time of the injection and in amniotic fluid and cord serum samples collected at delivery. Iodothyronine concentrations also were determined on cord samples from 24 full term control infants. The geometric mean serum T4 concentration in the experimental infants was 27.2 micrograms/dl, almost 3 times that of the control population (10.3 micrograms/dl); serum rT3 concentrations were markedly elevated to a mean of 657 ng/dl, compared to 254 ng/dl in control infants. The mean serum T3 concentration was slightly but significantly increased to 61.3 ng/dl (control, 48.3 ng/dl; P less than 0.02). Amniotic fluid T4, T3, and rT3 concentrations all increased significantly. T4 injection into the amniotic fluid is an effective method of increasing fetal serum T4 concentrations. The preferential pathway of monodeiodination of the injected T4 in the human fetus is to rT3 rather than T3.

Subhourly variability of circulating third trimester maternal steroid concentrations as a source of sampling error.

Seven plasma samples from five normal third trimester pregnant women, drawn every 5 and 15 min at similar times on 2 days, 2 days apart, were measured in quadruplicate for estradiol (E2), estriol, progesterone, 16 alpha-hydroxyprogesterone, and 17 alpha-hydroxyprogesterone (17P). The mean of the 22 samples obtained from each subject for each steroid was used as a reference mean. Individual determinations were converted to percentages of the reference mean which was normalized to 0%. All pregnancies were uncomplicated, and all mean values were within the normal range for gestational age. Variability about the reference mean for single samples, however, range from a low of -80% to a high of 150%. The single sample, 95% confidence intervals for individual steroids pooled from the five subjects (110 determinations) range from +/- 36% (E2) to +/- 60% (17P). Mean percentage coefficients of variation between 5-min and 15-min sampling sequences were compared by analysis of variance. There is no significant difference between the mean percentage coefficients of variation of a 5-min as opposed to a 15-min sampling sequence for any of the hormones measured. The 95% confidence interval width around the reference mean is a function of the number of samples obtained. Because the 95% confidence interval width from 110 measurements decreases approximately as 1/ square root n with increasing sampling size, the decrement progressively diminishes. For E2, the least variable steroid, a one-sample 95% confidence interval width of +/- 36% decreases to approximately +/- 18% with four samples or approximately +/- 12% with nine samples. For 17P, the most variable steroid, a one-sample 95% confidence interval width of +/- 60% decreases to approximately +/- 30% with four samples or approximately +/- 20% with nine samples. Multiple sampling with plasma pooling is required for the accurate study of steroid concentrations in individual subjects in late pregnancy.

Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. II. C18 and C19 steroids: estradiol, estriol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, delta 5-androstenediol, delta 4-androstenedione, testosterone, and dihydrotestosterone.

This report describes aggregate time trend effects of advancing gestational age on circulating maternal concentrations of 17beta-estradiol (E2), estriol (E3), dehydroepiandrosterone (D), dehydroepiandrosterone sulfate (D-S), delta 5-androstenediol (delta 5 diol), delta 4-androstenedione (delta 4 A), testosterone (T), and dihydrotestosterone (DHT) in a sequential series of 155 blood samples obtained from 19 normal pregnant women ranging from 26-40 weeks gestational age. Only E2, E3, and D-S show aggregate time trend effects. Log (E2) plots as a linear positive sloping curve from 26-40 weeks. Log (E3) plots as a positive sloping curve that is significantly steeper than log (E2) (P less than 0.05). Log (D-S) plots into a negative sloping curve which mirrors the pattern for log (E2) but cannot be statistically associated with log (E2) except for the opposite sign of their slopes, which are both significantly different from a zero slope (P less than 0.05). delta 4 A, T, DHT, delta 5 diol, and D show no aggregate time trends; however wide, comoving undulations for delta 4 A, T, DHT, and delta 5 diol between 26-28 and 38-40 weeks are confirmed in time by comparison of log mean plots and in magnitude by regressing the C19 steroids on one another. D shows virtually no association with the other C19 steroids. All C19 steroids, except for T, circulate at nonpregnant concentrations, implying that there is little placental secretion of these steroids into the maternal circulation.

Simultaneous comparison of delta 5-3beta-hydroxysteroid levels in the fetoplacental circulation of normal pregnancy in labor and not in labor.

Concentrations of pregnenolone (delta5P), dehydroepiandrosterone (DHEA), 16alpha-hydroxydehydroepiandrosterone (16alpha-OH DHEA), pregnenolone sulfate (delta5P-S), and dehydroepiandrosterone sulfate (DHEA-S) were measured simultaneously by radioimmunoassay in individual, paired umbilical artery (UA) and vein (UV) sera from 18 normal term pregnancies, 6 in labor, 12 not in labor. Mean UA and UV levels +/- SEM (ng/ml) were for delta5P: 30.39 +/- 1.69, 35.55 +/- 3.06; DHEA: 12.31 +/- 2.34, 3.66 +/- 0.38; 16alpha-OH DHEA: 7.48 +/- 0.63, 10.59 +/- 0.78; delta5P-S: 1,652 +/- 154, 1,486 +/- 130; DHEA-S: 2,122 +/- 134, +/- 134, 1,906 +/- 134. Umbilical artery delta5P-S, DHEA-S, and DHEA levels were significantly higher than UV levels, whereas the reverse was true for delta5P and 16alpha-OH DHEA. The inverse arterio-venous (A-V) gradient for 16alpha-OH DHEA was contrary to previous published reports using pooled samples. Comparison by linear regression of paired UA and UV steroid concentrations of delta5P, delta5P-S, DHEA, and DHEA-S revealed a significant correlation (P less than 0.01) for each steroid. Labor was associated with a significant increase in UA levels of DHEA-S and a smaller, but not quite significant, increase in UA levels of delta5P-S, while similar changes for unconjugated delta5-3beta-hydroxysteroids were not observed. Mean A-V gradients between the group of patients in labor and those not in labor were not significantly different. These data demonstrate that: 1) a significant difference between UA and UV concentrations exists for delta5P, DHEA, 16alpha-OH DHEA, delta5P-S, and DHEA-S; 2) there is a significant correlation between UA and UV concentrations for delta5P, DHEA, delta5P-S, and DHEA-S, implying that each fetoplacental unit maintains an equilibrium relative to these steroid concentrations in the umbilical circulation; 3) labor is associated with a significant increase in UA levels of DHEA-S and probably of delta5P-S.

Differential response of ovine placental lactogen levels in maternal and fetal circulations following single umbilical artery ligation in fetal sheep.

We investigated circulating maternal and fetal serum concentrations of ovine placental lactogen (oPL) following single umbilical artery ligation (SUAL) at 108 to 114 days' gestation. Ovine placental lactogen was isolated and purified from placental cotyledons, and a radioimmunoassay developed using previously described methods. Intrauterine growth retardation (IUGR) was manifest as increasing fetal brain-to-liver weight ratio with increasing duration of survival following SUAL. During the first five to seven days following SUAL, circulating oPL levels in ewes with SUAL fetuses were significantly reduced when compared with levels in ewes with control fetuses. In contrast, oPL levels in SUAL fetuses were significantly increased above levels in control fetuses for the first five to seven days following surgery. Fetal ovine growth hormone levels were elevated in SUAL fetuses, while ovine prolactin levels were similar in the two groups. IUGR was associated with mild fetal acidosis and fetal plasma CAT levels which were similar in SUAL and control fetuses. No correlation was found between fetal pH or CAT and fetal oPL levels. These findings are consistent with the view that circulating levels of oPL in the mother are related to the mass of functioning trophoblast. Elevated fetal oPL levels following SUAL may result from acute placental ischaemia with alterations in placental lactogen secretion at the maternofetal interface.

Corticotrophin-releasing hormone and CRH-binding protein. Differences between patients at risk for preterm birth and hypertension.

BACKGROUND: During pregnancy in the second and third trimester there is a progressive rise in plasma CRH thought to be secreted by the placenta. Plasma CRH-BP inactivates CRH, which may prevent its peripheral action on the maternal pituitary and myometrium. In the last few weeks of pregnancy CRH-BP decreases, thereby causing an increase in free CRH or a CRH/CRH-BP complex available to play a role in the onset of parturition. OBJECTIVE: We tested the hypothesis that differences in CRH, CRH-BP, or a CRH/CRH-BP complex in patients at risk for preterm birth (PTB) and hypertension (HYP) account for the differences in the timing of parturition. METHODS: From a Behavior in Pregnancy Study database, we identified 18 patients who had spontaneous PTB and 23 patients who developed HYP. Both groups were case controlled and matched with patients who delivered at term (Normal). Maternal plasma samples had been appropriately collected from these patients at 18-20, 28-30, and 35-36 weeks gestational age. CRH levels were measured by double antibody RIA kit and the CRH-BP by a immunoradiometric technique. A CRH-BP/CRH dimer complex index was calculated. Statistical analysis was done using Kruskal-Wallis test for two cases. RESULTS: Maternal CRH (pg/ml) in the PTB cases compared to the HYP cases was significantly elevated at all three time periods. Maternal CRH-BP (pg/ml) in the PTB versus HYP cases was significantly lower at all three time periods in the PTB cases compared to the HYP cases. Maternal CRH-BP/CRH dimer complex index was significantly lower in the PTB cases at all three time periods than either the controls or the HYP cases, suggesting excessive CRH. The mean GA at delivery for the PTB cases was significantly lower than the control or HYP cases. CONCLUSIONS: These results suggest that those patients at risk for PTB have significantly elevated CRH, lower CRH-BP, and a reduced CRH-BP/CRH dimer complex index at all three time periods of assessment.

Prenatal and perinatal factors associated with brain disorders.

In April 1985, a report entitled "Prenatal and Perinatal Factors Associated with Brain Disorders" was published by the National Institutes of Child Health and Human Development and the National Institute of Neurological and Communicative Disorders and Stroke. A panel of ten individuals completed the report documenting the knowledge and the complexities of what is known with respect to brain damage that may develop before birth or in the neonatal period. It is clear that all stages of fetal and neonatal development influence normal outcome. Although intrapartal period events may explain a significant portion of cerebral palsy, the illness is often linked with confounding factors such as low birth weight and asphyxia. Pure epilepsy or pure mental retardation is rarely associated with intrapartal events. In general, the pathologic lesions seen in the brain may reflect many different fetal insults. The same clinical event such as asphyxia may result in varied intracranial diseases, which effects may depend on when the clinical events occurred.

Maternal tobacco use and substance abuse: reported prevalence rates and associations with the delivery of small for gestational age neonates.

OBJECTIVE: To determine the changes in reported prevalence rates of tobacco use and substance abuse in a population of pregnant women, as well as to evaluate the associations between such use and sociodemographic characteristics and the delivery of small for gestational age (SGA) neonates. METHODS: We studied 7741 women who delivered at Cedars-Sinai Medical Center from 1986-1990. Antenatal and delivery information was entered prospectively into the computerized perinatal data base. Subjects were classified according to tobacco use and substance abuse status. We defined SGA as a birth weight less than the tenth percentile for gestational age at delivery. Univariate and multivariate analyses were used to determine the associations between SGA and tobacco use, substance abuse, and sociodemographic characteristics. RESULTS: We found that the reported prevalence rates of tobacco use and substance abuse declined between 1986-1990 (10 versus 6% and 7 versus 2%, respectively; P < .001). Tobacco use and substance abuse were reported as being highest in black women (11 and 6%) and lowest in Asian and Hispanic women (4 and 3%), a significant difference (P < .001). Tobacco use and race-ethnicity were found to have the strongest independent associations with SGA. The incidence of SGA was highest in black women identified as tobacco users and substance abusers. CONCLUSIONS: The reported rates of tobacco use and substance abuse varied by year, race-ethnicity, and insurance status. There were significant associations between maternal tobacco use, substance abuse, and race-ethnicity and the incidence of SGA neonates.

Institute of Medicine maternal weight gain recommendations and pregnancy outcome in a predominantly Hispanic population.

OBJECTIVES: To describe gestational weight gain patterns by pre-pregnancy weight and trimester of pregnancy, and to examine the risk of preterm birth associated with pre-pregnancy weight and gestational weight gain using various definitions of adequacy based on the Institute of Medicine (IOM) standard. METHODS: We used data collected prospectively from 8736 pregnant women receiving care in public health clinics in the West Los Angeles area. Pre-pregnancy weight was based on self-report obtained at the initial visit. Maternal weight was measured at each prenatal visit, allowing for the calculation of total weight gain and the rate of weight gain during each trimester. RESULTS: Women underweight before pregnancy (body mass index less than 19.8) had the greatest risk of delivering preterm (crude relative risk 1.7, P < .05). Similarities in patterns of weight gain were seen between women of low weight and normal pre-pregnancy weight status, as well as between overweight and obese women. Compared to the IOM recommendations for total weight gain, 47.8% of underweight women and 36.6% of normal-weight women gained the recommended amount. In contrast, 52% and more than 75% of overweight and obese women, respectively, had excessive gains. Inadequate weight gain during the third trimester as opposed to excessive gain, defined specifically for each pre-pregnancy weight status, was predictive of preterm birth. CONCLUSIONS: Weight monitoring during pregnancy continues to have clinical applications for the prediction of poor birth outcomes. Weight gain less than 90% the IOM recommendation in the third trimester may serve as an indicator for identifying women at risk of delivering preterm.

An algorithm for determining gestational age from unconjugated estriol levels.

Between the 30th and 40th weeks of gestational age (GA), plasma unconjugated estriol (E3) concentrations plotted as a logarithmic function of GA describe a complex bimodal curve. The maximum concentrations for the first peak (GAmax1) occur at approximately 34 weeks' GA, those for the second peak (GAmax2) occur at approximately 38 weeks' GA, and a between-mode nadir occurs at 35 weeks' GA. Using the close relationship between the features of this curve and GA, a computerized algorithmic curve analysis is devised for the estimation of GA during the third trimester of pregnancy. This report describes the algorithm, its clinical application, and its preliminary performance.

Late meconium passage in labor--a sign of fetal distress?

Although the passage early in labor of thick amniotic fluid heavily stained with meconium is recognized as an indication of potential fetal asphyxia, the significance of late passage of meconium-stained fluid in labor is less certain. One hundren twenty-eight patients with late passage of meconium in labor and 134 control patients were examined, using chi 2 and discriminant analysis, to determine if any relationships existed between fetal heart rate (FHR) patterns, late passage of meconium in labor, and neonatal morbidity. In the group with late meconium passage, adequate baseline FHR variability and nonperiodic accelerations were predictive of high Apgar scores, and repeated (over 20) variable decelerations were predictive of low Apgar scores. In the control group, none of the FHR patterns examined were predictive of Apgar score. Thus, the combination of late passage of meconium in labor with other intrapartum signs may indicate a fetus at risk for asphyxia when neither sign alone is predictive. The presence of late meconium passage demands close observation of the patient in labor, including assessment by electronic FHR monitoring.

Fetal and maternal copper levels in patients at term with and without premature rupture of membranes.

This study evaluated the relationship between serum copper levels and premature rupture of the membranes (PROM). Serum copper levels are significantly lower in fetuses and their mothers with PROM at term as compared with a control group without PROM. Birth weights of the newborns delivered following PROM are significantly lower than those in the control group despite similarity of gestational ages. The significance of these findings is discussed.

Uterine leiomyomas in pregnancy: a prospective study.

Uterine leiomyomas are associated with various complications during pregnancy. During a 2-year period, pregnant women with a history of leiomyomas were referred to our antenatal testing unit for ultrasound evaluation. Eighty-five patients were found to have single or multiple leiomyomas by ultrasound examination. The size (total leiomyoma volume), number, and location of the leiomyoma(s) were ascertained. Each woman with leiomyoma(s) was matched by age, race, and parity with one without leiomyomas. Both groups were followed throughout pregnancy, and outcomes were compared. Size, number, or location of the leiomyoma had no influence on outcome. Student t test indicated a significantly (P less than .01) lower mean gestational age at the time of delivery in women with leiomyomas.

Perinatal outcome in triplet versus twin gestations.

The present study was conducted to determine whether triplet pregnancies are associated with a significantly worse perinatal outcome than twin pregnancies. Maternal and neonatal outcome was evaluated in 15 triplet and twin pregnancies that were matched for maternal age, race, type of medical insurance, delivery mode, parity, and history of previous preterm delivery. Preterm labor occurred significantly more often in triplet than in twin gestations (80 versus 40%), as did preterm delivery (87 versus 26.7%). Triplets had a significantly lower mean birth weight (1720 versus 2475 g) and gestational age at delivery (33 versus 36.6 weeks). In addition, 53.3% of triplet pregnancies but only 6.7% of twin pregnancies had one or more neonates with intrauterine growth retardation. Discordancy also occurred more frequently in triplets than in twins (66.7 versus 13.3%). The mean averaged neonatal hospital stay was significantly higher in triplets (29 versus 8.5 days), and triplets had a fivefold increased risk of requiring neonatal intensive care as compared with twins. However, there were no significant differences between the groups in maternal morbidity or major neonatal complications such as respiratory distress syndrome or intraventricular hemorrhage. We believe that these data will be useful in counseling patients with respect to the anticipated perinatal outcome of triplet pregnancies.

The biophysical profile in labor.

To determine whether the biophysical profile would be a valuable intrapartum addition to fetal heart rate monitoring in predicting umbilical arterial acid-base status at delivery, 95 patients at term had serial studies during labor and umbilical artery blood gas analysis. There was no significant association between biophysical profile score and cord blood pH, nor was there a difference in scores between the acidemic and nonacidemic groups. Of the five components of the initial biophysical profile, only a nonreactive nonstress test (NST) was associated with both pH 7.20 or less (P = .019) and metabolic acidemia (P = .016). None of the individual variables of the final examination correlated with a pH of 7.20 or less. However, a nonreactive NST was associated with metabolic acidemia (P = .03), as was the presence of breathing (P = .03). Of the ten infants with pH 7.20 or less, eight had an initial and five had a final biophysical profile score of 8 or higher. Of the five whose pH was less than 7.15, four had an initial and three a final score of 8 or more. Finally, of the five with metabolic acidemia, four had an initial and two a final score of 8 or higher. Half of the acidemic fetuses had final biophysical profile scores of 8 or higher, suggesting that this score in labor is not reliable to rule out acidemia at delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Repeat cesareans: how many are elective?

OBJECTIVE: To describe the clinical indications for repeat cesarean delivery and to compare these with indications for primary procedures. METHODS: We reviewed cesarean deliveries at our academic nonprofit hospital during 1992 (n = 1885). The indication for the procedure was abstracted based on surgeon operative reports and discharge ICD-9 codes (International Classification of Diseases, Clinical Modification, 9th Edition). RESULTS: The hospital cesarean rate was 28.7%; 34% of these were repeat procedures (n = 643). Elective cesarean delivery was the leading cause of repeat cesareans, followed by "other" indications, dystocia, breech, and fetal distress. In contrast, dystocia was the leading cause for primary cesarean, followed by fetal distress, "other," and breech presentation. One hundred women (15.6%) undergoing repeat cesarean had absolute or relative contraindications to a trial of labor. CONCLUSIONS: Indications for cesareans using hierarchies based on ICD-9 codes do not attempt to differentiate categories of indications for repeat cesarean. Current recommendations for lowering cesarean rates by increasing vaginal birth after previous cesarean are based on aggregate data and do not recognize that some repeat cesareans are clinically indicated. A coding system designed to distinguish elective from indicated repeat cesareans would be useful for future prospective studies.

Bupivacaine paracervical block. Effects on the fetus and neonate.

To evaluate effects on the fetus and neonate, 53 paracervical blocks were administered to 38 low-risk parturients using a controlled superficial injection of 0.25% bupivacaine. Continuous fetal heart rate monitoring revealed no instance of bradycardia or late deceleration pattern. Apgar scores, cord arterial and venous pH values, and neurobehavioral evaluations of the neonates were similar to those observed in other low-risk patients. The effectiveness of pain relief of the blocks was less than expected or reported by other authors. Although we observed no harmful effects on the fetus or neonate from the superficial paracervical injection of bupivacaine, we did not find this combination of drug and technique to give dependable, effective pain relief in labor.

Fetal catecholamine release in response to labor and delivery.

Umbilical arterial plasma norepinephrine and epinephrine were measured using a sensitive, specific radioenzymatic assay. Plasma catecholamines were correlated with umbilical arterial blood gases, durations of the first and second stages of labor, duration of rupture of the membranes, fetal heart rate tracings, and fetal sex. Significant correlations were observed for plasma norepinephrine versus fetal pH and PO2 and plasma epinephrine versus pH but not PO2. The majority of the fetal heart rate tracings demonstrated either a normal baseline or mild variable decelerations. The plasma catecholamines and blood gases were similar in these 2 groups. Significant elevations of both plasma catecholamines were observed with those tracings commonly associated with fetal distress; however, the number of infants was small. No sex differences were observed in plasma norepinephrine or epinephrine or in responsiveness. The results suggest that the human fetus at term responds to acidosis and hypoxia with a graded catecholamine release. This may be an important adaptive mechanism.

Time trend analysis of unconjugated estriol concentrations in third-trimester pregnancy.

Utilizing a plasma pooling procedure to control short-term pulsatile variability of unconjugated estriol (E3) concentrations, the authors evaluated time trend curves in 42 subjects after normalizing time trend curves in 42 subjects after normalizing gestational age (GA) by a computerized algorithm. Semilogarithmic plots from individual subjects and a median plot derived from pooling the 42 subjects describe complex bimodal curves beginning with an initial steep rise at 30 to 32 weeks' GA, a peak between 32 and 34 weeks' Ga, a transient nadir at 35 weeks' GA, a second steep rise between 35 and 37 weeks' Ga, a second peak between 37 and 39 weeks' Ga, and a downward segment just prior to parturition. Predicted GAs at delivery obtained from individual curve analyses concurred with pediatric GAs within 2 weeks or less in 41 or 42 pregnancies.