General anesthesia for cesarean delivery and childhood neurodevelopmental and perinatal outcomes: a secondary analysis of a randomized controlled trial.

BACKGROUND: In 2016, the U.S. Food and Drug Administration expressed concern that neurodevelopment may be negatively affected by anesthesia or sedation exposure in pregnancy or before three years of age. We examined the association between general anesthesia at the time of cesarean delivery and early childhood neurodevelopment. METHODS: A secondary analysis of a multicenter randomized controlled trial assessing magnesium for prevention of cerebral palsy in infants at risk for preterm delivery. Exposure was general compared to neuraxial anesthesia. The primary outcome was motor or mental delay at two years of age, assessed by Bayley Scales of Infant Development II (BSIDII). Secondary outcomes included BSIDII subdomains and perinatal outcomes. Multivariable logistic regression models were performed to control for confounders. RESULTS: Of 557 women undergoing cesarean delivery, 119 (21%) received general anesthesia. There were no differences in the primary composite outcome of developmental delay (aOR 0.93, 95% CI 0.61 to 1.43) or the BSIDII subdomains of mild, moderate, or severe mental delay, or mild or moderate motor delay. Severe motor delay was more common among infants exposed to general anesthesia (aOR 1.98, 95% CI 1.06 to 3.69). Infants exposed to general anesthesia had longer neonatal intensive care stays (51 vs 37 days, P=0.010). CONCLUSIONS: General anesthesia for cesarean delivery was not associated with overall neurodevelopmental delay at two years of age, except for greater odds of severe motor delay. Future studies should evaluate this finding, as well as the impact on neurodevelopment of longer or multiple anesthetic exposures across all gestational ages.

A randomized trial of the effects of coached vs uncoached maternal pushing during the second stage of labor on postpartum pelvic floor structure and function.

OBJECTIVE: The purpose of this study was to determine if refraining from coached pushing during the second stage of labor affects postpartum urogynecologic measures of pelvic floor structure and function. STUDY DESIGN: Nulliparous women at term were randomized to coached (n = 67) vs uncoached (n = 61) pushing. At 3 months' postpartum women underwent urodynamic testing, pelvic organ prolapse examination (POPQ), and pelvic floor neuromuscular assessment. RESULTS: Urodynamic testing revealed decreased bladder capacity (427 mL vs 482 mL, P = .051) and decreased first urge to void (160 mL vs 202 mL, P = .025) in the coached group. Detrusor overactivity increased 2-fold in the coached group (16% vs 8%), although this difference was not statistically significant (P = .17). Urodynamic stress incontinence was diagnosed in the coached group in 11/67 (16%) vs 7/61 (12%) in the uncoached group (P = .42). CONCLUSION: Coached pushing in the second stage of labor significantly affected urodynamic indices, and was associated with a trend towards increased detrusor overactivity.

Outcomes among term infants when two-hour postnatal pH is compared with pH at delivery.

OBJECTIVE: This study was undertaken to measure infant outcomes when pH at birth was compared with neonatal pH determined within 2 hours of age. STUDY DESIGN: We retrospectively studied term infants born between January 1, 1988, and August 31, 1998, who had umbilical artery blood pH measured at birth and again from the radial artery or umbilical artery within 2 hours after birth. Statistical significance was determined with the chi2 test. Odds ratios and 95% confidence intervals were calculated by means of the Mantel-Haenszel method. RESULTS: Data from a total of 1691 infants were analyzed: 178 (11%) had acidemia at birth (pH of <7.20) that persisted through the first 2 hours after birth; 110 (6%) had development of acidemia after birth; and 594 (35%) were born with a cord pH of <7.20 that improved after delivery. The remaining 809 infants (48%) did not have acidemia either at birth or during the neonatal period, and these served as the reference group. Seizures during the first 24 hours after birth were more likely among those infants with persistent acidemia (odds ratio, 13.0; 95% confidence interval, 6.3-26.7). The odds ratio for seizures among infants in whom acidemia developed after birth was 5.7 (95% confidence interval, 2.2-14.5). Other than the reference group, the infants who were born with acidemia that was corrected by 2 hours after birth had the lowest risk of seizures (odds ratio, 2.5; 95% confidence interval, 1.2-5.3). Significant differences in neonatal outcomes persisted after correction for anomalies. CONCLUSION: The direction of pH change from birth to the immediate neonatal period was significantly related to morbidity and mortality among term infants who were ill at birth or became ill shortly thereafter.

The continuing value of the Apgar score for the assessment of newborn infants.

BACKGROUND: The 10-point Apgar score has been used to assess the condition and prognosis of newborn infants throughout the world for almost 50 years. Some investigators have proposed that measurement of pH in umbilical-artery blood is a more objective method of assessing newborn infants. METHODS: We carried out a retrospective cohort analysis of 151,891 live-born singleton infants without malformations who were delivered at 26 weeks of gestation or later at an inner-city public hospital between January 1988 and December 1998. Paired Apgar scores and umbilical-artery blood pH values were determined for 145,627 infants to assess which test best predicted neonatal death during the first 28 days after birth. RESULTS: For 13,399 infants born before term (at 26 to 36 weeks of gestation), the neonatal mortality rate was 315 per 1000 for infants with five-minute Apgar scores of 0 to 3, as compared with 5 per 1000 for infants with five-minute Apgar scores of 7 to 10. For 132,228 infants born at term (37 weeks of gestation or later), the mortality rate was 244 per 1000 for infants with five-minute Apgar scores of 0 to 3, as compared with 0.2 per 1000 for infants with five-minute Apgar scores of 7 to 10. The risk of neonatal death in term infants with five-minute Apgar scores of 0 to 3 (relative risk, 1460; 95 percent confidence interval, 835 to 2555) was eight times the risk in term infants with umbilical-artery blood pH values of 7.0 or less (180; 95 percent confidence interval, 97 to 334). CONCLUSIONS: The Apgar scoring system remains as relevant for the prediction of neonatal survival today as it was almost 50 years ago.

Predictive value of serial middle cerebral and renal artery pulsatility indices in fetuses with oligohydramnios.

OBJECTIVE: To determine if unexplained changes in the amniotic fluid index or pulsatility indices of the fetal renal, middle cerebral, or umbilical artery are predictive of perinatal outcome in pregnancies complicated by oligohydramnios. METHODS: Changes in amniotic fluid measurements and fetal vessel velocimetry in patients with oligohydramnios were evaluated for correlation with fetal outcome. Fourteen fetuses with oligohydramnios underwent serial sonography evaluating the amniotic fluid index and fetal middle cerebral, renal, and umbilical velocimetry. Matched controls and neonatal outcomes were obtained. RESULTS: Change in amniotic fluid index and in renal artery pulsatility index were inversely correlated. Change in the middle cerebral artery pulsatility index was different in infants with normal outcome compared to infants with adverse outcome CONCLUSIONS: Serial velocimetry of the middle cerebral artery may identify fetuses with oligohydramnios at risk for adverse outcomes.

Pregnancy outcomes after antepartum diagnosis of oligohydramnios at or beyond 34 weeks' gestation.

OBJECTIVE: Our purpose was to assess whether antepartum oligohydramnios is associated with adverse perinatal outcomes. STUDY DESIGN: Women delivered between July 1, 1991, and September 30, 1996, who underwent ultrasonography at >/=34 weeks' gestation were analyzed. Oligohydramnios was defined as an amniotic fluid index 50 mm. RESULTS: In our analysis of 6423 pregnancies, 147 (2.3%) were complicated by oligohydramnios. This complication was associated with increased labor induction (42% vs 18%; P <.001), stillbirth (1. 4% vs 0.3%; P <.03), nonreassuring fetal heart rate (48% vs 39%; P <. 03), admission to the neonatal intensive care nursery (7% vs 2%; P <. 001), meconium aspiration syndrome (1% vs 0.1%; P <.001), and neonatal death (5% vs 0.3%; P <.001). CONCLUSION: Antepartum oligohydramnios is associated with increased perinatal morbidity and mortality.

Birth weight in relation to morbidity and mortality among newborn infants.

BACKGROUND: At any given gestational age, infants with low birth weight have relatively high morbidity and mortality. It is not known, however, whether there is a threshold weight below which morbidity and mortality are significantly greater, or whether that threshold varies with gestational age. METHODS: We analyzed the neonatal outcomes of death, five-minute Apgar score, umbilical-artery blood pH, and morbidity due to prematurity for all singleton infants delivered at Parkland Hospital, Dallas, between January 1, 1988, and August 31, 1996. A distribution of birth weights according to week of gestation at birth was created. Infants in the 26th through 75th percentiles for weight served as the reference group. Data on preterm infants (those born at 24 to 36 weeks of gestation) were analyzed separately from data on infants delivered at term (37 or more weeks of gestation). RESULTS: A total of 122,754 women and adolescents delivered singleton live infants without malformations between 24 and 43 weeks of gestation. Among the 12,317 preterm infants who were analyzed, there was no specific birth-weight percentile at which morbidity and mortality increased. Among 82,361 infants who were born at term and whose birth weights were at or below the 75th percentile, however, the rate of neonatal death increased from 0.03 percent in the reference group (26th through 75th percentile for weight) to 0.3 percent for those with birth weights at or below the 3rd percentile (P<0.001). The incidence of five-minute Apgar scores of 3 or less and umbilical-artery blood pH values of 7.0 or less was approximately doubled for infants at or below the 3rd birth-weight percentile (P=0.003 and P<0.001, respectively). The incidence of intubation at birth, seizures during the first day of life, and sepsis was also significantly increased among term infants with birth weights at or below the 3rd percentile. These differences persisted after adjustment for the mother's race and parity and the infant's sex. CONCLUSIONS: Mortality and morbidity are increased among infants born at term whose birth weights are at or below the 3rd percentile for their gestational age.

Placental transfer of ritonavir with zidovudine in the ex vivo placental perfusion model.

OBJECTIVE: The object was to determine the placental transfer of ritonavir alone and in combination with zidovudine. STUDY DESIGN: Twelve placental perfusion studies were performed at trough (1-2 microg/mL) and peak (approximately 20 microg/mL) combinations of ritonavir and zidovudine. Accumulation of ritonavir was determined. RESULTS: Transfer of ritonavir at trough concentrations was undetectable (<0.025 microg/mL). The clearance index of ritonavir at peak concentration was 0.085 +/- 0.05 and was unaffected by zidovudine. The fetal concentration of ritonavir was 0.0758 +/- 0.22 microg/mL at a maternal concentration of approximately 20 microg/mL and 25.5 +/- 6.9 microg/mL at a concentration of 100 microg/mL. There was no tissue accumulation of ritonavir either alone or with zidovudine. CONCLUSION: The clearance index of ritonavir at therapeutic levels was extremely low, with little accumulation in the fetal compartment and no accumulation in placental tissue. Zidovudine does not significantly affect the transfer or accumulation of ritonavir.

Pregnancy outcomes in women with gestational diabetes compared with the general obstetric population.

OBJECTIVE: To compare pregnancy outcome in a homogeneous group of women with glucose intolerance with that of women without this disorder. METHODS: This was a retrospective cohort study of all women with singleton cephalic-presenting pregnancies delivered at University of Texas Southwestern Medical Center during the period January 1, 1991, through December 31, 1995. During this period, women were screened selectively for glucose intolerance and National Diabetes Data Group thresholds were used to diagnose gestational diabetes. Women with class A1 gestational diabetes were compared with nondiabetic women within the cohort. Effects of confounding variables were analyzed using multiple logistic regression and a matched-control comparison. Controls were matched according to ethnicity, maternal age, maternal weight, and parity. RESULTS: A total of 61,209 nondiabetic women with singleton cephalic pregnancies were delivered during the study period, and 874 were diagnosed with class A1 gestational diabetes. Women with class A1 gestational diabetes were significantly older, heavier, of greater parity, and more often of Hispanic ethnicity. Hypertension (17 versus 12%), cesarean delivery (30 versus 17%), and shoulder dystocia (3 versus 1%) were significantly increased (all P < .001) in these women compared with the general obstetric population. Infants born to women with class A1 gestational diabetes were significantly larger (mean birth weight 3581 +/- 616 versus 3290 +/- 546 g, P < .001), and this accounted for the increased incidence of dystocia. The attributable risk for large for gestational age (LGA) infants due to class A1 gestational diabetes was 12%. CONCLUSION: The main consequence of class A1 gestational diabetes is excessive fetal size leading to increased risk of difficult labor and delivery. We estimate that approximately one of eight women with class A1 gestational diabetes mellitus delivers an LGA infant attributable to glucose intolerance.

Intraventricular hemorrhage and fetal heart rate in very low birth weight infants.

OBJECTIVE: This study was designed to investigate the relationship between fetal heart rate patterns before delivery and periventricular-intraventricular hemorrhage in the very low birth weight infant. STUDY DESIGN: The last 30 minutes of electronic fetal heart rate data preceding delivery were analyzed for 84 singleton infants weighing between 700 and 1500 gm. All these infants received serial cranial ultrasonographic examinations commencing within 24 to 48 hours of birth. RESULTS: Thirty-three fetuses had normal heart rate patterns, and 51 had fetal heart rate abnormalities. Periventricular-intraventricular hemorrhage was not associated with fetal heart rate abnormalities. Univariate and multivariate regression analysis demonstrated that only gestational age < 28 weeks was a significant contributing factor to periventricular-intraventricular hemorrhage (odds ratio 2.2, 95% confidence interval [CI], 1.0 to 4.8). CONCLUSION: Fetal heart rate patterns immediately preceding delivery are not predictive of periventricular-intraventricular hemorrhage in the very low birth weight infant.

Chorioamnionitis and endometritis.

Chorioamnionitis complicates 1% to 2% of all pregnancies and may affect 10% of women with certain risk factors. Intraamnionic infection may result in devastating morbidity for both the fetus and the mother. Also, chorioamnionitis is associated with higher cesarean section rates. As demonstrated earlier, endometritis is a common complication of cesarean delivery alone. Nevertheless, antibiotic prophylaxis has been shown to reduce postpartum morbidity. In the face of chorioamnionitis and a cesarean delivery, the risk of developing endometritis increases exponentially. However, if appropriate antibiotic therapy is instituted at the time of diagnosis, fetal and maternal outcomes improve dramatically. Similar to chorioamnionitis, endometritis is usually polymicrobial in nature. The preponderance of the organisms isolated are anaerobic. Established risk factors include operative delivery, prolonged ruptured fetal membranes, and prolonged labor. The diagnosis is based primarily on clinical examination with fever and the exclusion of other sources of extrapelvic infection. Once the diagnosis is established, appropriate empiric antibiotics are instituted. Antibiotic therapy should be continued until the patient is afebrile and asymptomatic for 24 to 36 hours. Over the past 20 years, the use of single-agent therapy in these serious infections has been shown to be safe as well as effective. Once successful therapy is completed, the patient is discharged home with no oral antibiotics.

Cholecystitis in pregnancy.

Biliary tract disease is a relatively uncommon, heterogenous disease in pregnancy. Specifically, acute cholecystitis can be especially difficult to recognize in pregnancy. However, once diagnosed, the initial management plan should be conservative and include antibiotic therapy. Subsequent management depends on the gestational age at diagnosis. Surgical therapy, when indicated, should not be delayed and a planned intervention during the second trimester appears to offer a better outcome than surgery performed under emergent conditions.