Effect of early-onset sepsis evaluations on in-hospital breastfeeding practices among asymptomatic term neonates.

OBJECTIVE: To examine the effect of separation for early-onset sepsis (EOS) evaluations due to perinatal risk factors on breastfeeding practices among asymptomatic term newborns. METHODS: This observational study included 692 nulliparous women with term, singleton uncomplicated pregnancies who intended to breastfeed and whose infants were well appearing at birth. We examined the rate of early breastfeeding initiation (within 2 hours of birth) and formula supplementation (in the first 24 hours) among this mother-infant cohort. RESULTS: Asymptomatic infants separated for EOS evaluation within 2 hours of birth were more likely to have delayed initiation of breastfeeding (46.5% vs 12.5%; P<.001). This association remained significant when adjusted for potential confounders (adjusted odds ratio [aOR]: 5.5 [95% confidence interval (CI): 3.4-8.9]; P<.001). Among infants separated for EOS evaluation, mother-infant time together of ≤0.5 hour in the first 2 hours of life significantly delayed initiation (aOR: 8.9 [95% CI: 1.5-53.7]; P=.02) compared with infants spending >1.5 hours with their mothers. In bivariate analysis, both separation and initiation were associated with formula supplementation. After adjusting for confounders, only delayed initiation remained significantly associated with supplementation (aOR: 1.9 [95% CI: 1.1-3.5]; P=.03). CONCLUSIONS: Early separation of asymptomatic infants from their mothers for EOS evaluation was significantly associated with delayed initiation of breastfeeding, which in turn was associated with increased formula supplementation in the first day of life. This unintended consequence of EOS evaluations among asymptomatic infants may be minimized by delaying early separation for performance of the evaluation, attempting breastfeeding initiation before separation, and/or applying more efficient criteria for identifying infants requiring evaluation.

Is cryopreservation of embryos a legitimate surrogate marker of embryo quality in studies of assisted reproductive technology conducted using national databases?

OBJECTIVE: To investigate whether cryopreservation of supernumerary embryos is a good surrogate for embryo quality. DESIGN: Retrospective study of 6,859 assisted reproductive technology (ART) cycles from women aged <35 years with two fresh day 3 embryos transferred. SETTING: National Society for Assisted Reproductive Technology Clinic Outcome Reporting System data from 2006-2008. PATIENT(S): Women undergoing ART. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryo quality (good, fair, or poor), cell number, and live births were compared for cycles with and without cryopreservation, using χ(2) to evaluate statistical significance. The association of freezing with embryo quality was examined using multiple logistic regression after adjusting for confounders (patient age, oocyte yield, intracytoplasmic sperm injection [ICSI], assisted hatching, male factor infertility). RESULT(S): Cycles with cryopreservation were more likely to have two embryos of good quality transferred (81.3% vs. 48.5%) and had more 8-cell embryos transferred (76.0% vs. 50.1%). Relative to cycles with two good embryos (good-good), the adjusted odds ratios (OR) for cryopreservation were: good-fair (OR = 0.301, 95% confidence interval [CI] = 0.257-0.354), fair-fair (OR = 0.308, 95% CI = 0.258-0.367), and any poor (OR = 0.058, 95% CI = 0.040-0.083). The live birth rate was 52.4% for cycles with freezing and 40.6% for cycles without. CONCLUSION(S): Embryo quality and cell number were both associated with embryo cryopreservation. However, although cryopreservation was a strong marker for good quality, not having cryopreservation did not reliably indicate poor quality, as almost half of those cycles had two good quality embryos.

Association of epidural-related fever and noninfectious inflammation in term labor.

OBJECTIVE: To investigate the role of infection and noninfectious inflammation in epidural analgesia-related fever. METHODS: This was an observational analysis of placental cultures and serum admission and postpartum cytokine levels obtained from 200 women at low risk recruited during the prenatal period. RESULTS: Women receiving labor epidural analgesia had fever develop more frequently (22.7% compared with 6% no epidural; P=.009) but were not more likely to have placental infection (4.7% epidural, 4.0% no epidural; P>.99). Infection was similar regardless of maternal fever (5.4% febrile, 4.3% afebrile; P=.7). Median admission interleukin (IL)-6 levels did not differ according to later epidural (3.2 pg/mL compared with 1.6 pg/mL no epidural; P=.2), but admission IL-6 levels greater than 11 pg/mL were associated with an increase in fever among epidural users (36.4% compared with 15.7% for 11 pg/mL or less; P=.008). At delivery, both febrile and afebrile women receiving epidural had higher IL-6 levels than women not receiving analgesia. CONCLUSION: Epidural-related fever is rarely attributable to infection but is associated with an inflammatory state.

Low-risk gestational trophoblastic neoplasia and methotrexate resistance: predictors of response to treatment with actinomycin D and need for combination chemotherapy.

OBJECTIVE: To determine whether any clinical parameters predict the need for multiagent chemotherapy for treatment of low-risk gestational trophoblastic neoplasia (GTN) after the development of methotrexate (MTX) resistance. STUDY DESIGN: We retrospectively analyzed clinical data from the New England Trophoblastic Disease Center from women with post-molar GTN between 1973 and 2003. RESULTS: We analyzed data from 150 women (40 with partial mole, 110 with complete mole) who received single-agent MTX for low-risk GTN using FIGO and WHO scoring systems. Of the 45 women who developed MTX resistance, the majority (37/45) of these patients received actinomycin D, with 10 patients ultimately requiring multiagent chemotherapy. The requirement for multiagent chemotherapy following MTX resistance was associated with a beta-hCG > 600 mlU/mL 1 week following initial MTX therapy (p < 0.03). Conversely, a beta-hCG < 600 mlU/mL 1 week following initial MTX therapy was as-sociated with a 93% probability of remission with actinomycin D alone. All patients went into durable remission. CONCLUSION: The prognosis for patients with low-risk GTN following molar gestation is excellent, with 100% remission rate, though a small but significant proportion (7%) required multiagent chemotherapy. The need for multiagent chemotherapy was associated with beta-hCG levels 1 week following initial MTX therapy.

Evaluating methotrexate treatment in patients with low-risk postmolar gestational trophoblastic neoplasia.

OBJECTIVE: To identify clinical factors associated with requiring more than a single course of Methotrexate (MTX) to achieve remission among women with low-risk postmolar gestational trophoblastic neoplasia (GTN). METHODS: We studied 150 women with persistent GTN after diagnosis of complete (n=110) or partial mole (n=40) to identify possible predictors of requiring additional treatment after a single treatment of methotrexate (MTX). All women had low-risk disease using FIGO and WHO scoring systems. RESULTS: Seventy women (47%) required additional courses of chemotherapy, of whom 45 (64%) received chemotherapy other than MTX. Multivariate analysis revealed that complete mole histology, presence of metastasis, single day MTX infusion and any increase in serum beta human chorionic gonadotropin (beta-hCG) level 1 week after MTX therapy were independent predictors of requiring additional MTX or alternative chemotherapy. Dilatation and curettage (D+C) within 1 week after the diagnosis of persistence did not affect future chemotherapy requirements (p>0.64). Following complete mole, beta-hCG levels >2000 mIU/mL at 1 week post MTX were associated with a 89% risk of additional cycles chemotherapy including MTX and a 65% risk of alternative chemotherapy. CONCLUSIONS: Metastatic disease, MTX infusion protocol and complete mole histology were independently associated with the need for additional chemotherapy after an initial course of MTX for women with low risk GTN. D+C at persistence did not alter the chemotherapy requirement. Elevated beta-hCG level at 1 week after the initial course of MTX was also an independent factor predicting the need for additional courses of MTX or alternative chemotherapy.

Postevacuation hCG levels and risk of gestational trophoblastic neoplasia among women with partial molar pregnancies.

OBJECTIVE: To develop human chorionic gonadotropin (hCG) criteria that determine a patient's risk of developing persistent gestational trophoblastic neoplasia (GTN) or achieving remission after partial mole evacuation. STUDY DESIGN: We used a database from the New England Trophoblastic Disease Center to analyze hCG levels from 284 women with partial molar pregnancies diagnosed between 1973 and 2003. RESULTS: An hCG level >199 mIU/mL in the third through eighth week following molar evacuation was associated with at least a 35% risk of GTN. CONCLUSION: Women with partial mole who have elevated hCG levels within the first few weeks after molar evacuation are at increased risk for developing GTN.

Clinical characteristics of persistent gestational trophoblastic neoplasia after partial hydatidiform molar pregnancy.

OBJECTIVE: To identify clinical characteristics associated with developing persistent gestational trophoblastic neoplasia (GTN) after partial hydatidiform molar pregnancy (PHM). STUDY DESIGN: Utilizing the Donald P. Goldstein in patients who developed persistence between 1973 and 1989. CONCLUSION: Older age at diagnosis and history of prior mole were significantly more common in women who developed persistence after partial molar pregnancy in referral of patients the earlier cohort but not in idefined clinical the recent cohort. In recent years no clinical factor was at increase their risk significantly associated with rsistence. database at the New England Trophoblastic Disease Center, 284 women with partial molar pregnancy diagnosed between 1973 and 2003 were characteristics identified. Clinical charac- for pe teristics, such as gravidity, parity, age, uterine size, gestational age at diagnosis, human chorionic gonadotropin levels at presentation and time to development of persistence (GTN) were analyzed. Data were also divided into 2 cohorts, an earlier one (1973-1989) and a later one (1990-2003), in order to look at potential changes over time. RESULTS: GTN developed in 5.6% of partial molar pregnancies. Older maternal age was significantly associated with development of persistent GTN in the earlier cohort but not in the recent cohort. Previous molar pregnancy was also statistically significantly more common the development of +/-after PHM.

Low risk of relapse after achieving undetectable HCG levels in women with partial molar pregnancy.

OBJECTIVE: We evaluated the risk of gestational trophoblastic neoplasia (GTN) for women with partial molar pregnancy whose human chorionic gonadotropin (hCG) levels fall spontaneously to undetectable levels using a sensitive hCG assay. METHODS: We analyzed data from the New England Trophoblastic Disease Center to estimate the risk of GTN among 284 women with partial molar pregnancy and at least 6 months of gonadotropin follow-up. RESULTS: None of the 238 women with complete gonadotropin follow-up and a spontaneous decline in serum hCG levels to undetectable levels subsequently developed GTN (95% confidence interval 0-1.6%). CONCLUSION: If these results are replicated at other institutions with longstanding experience managing partial molar pregnancies, it may be reasonable to abbreviate clinical follow-up for women with partial molar pregnancy whose serum hCG levels spontaneously decline to an undetectable level.

Obstetric and neonatal outcomes associated with maternal hypothyroid disease.

OBJECTIVE: We sought to determine whether women with treated hypothyroid disease were more likely than women without thyroid disease to suffer adverse obstetric or neonatal outcomes or to deliver a child with a congenital anomaly. METHODS: Using an institutional database, we identified women with treated hypothyroid disease (n = 482) who delivered a baby at our institution during a 33-month period. We compared the occurrence of adverse obstetric or neonatal outcomes among these women to the occurrence among women without thyroid disease (n = 19,487). RESULTS: Women with treated hypothyroid disease were not at increased risk for delivering a baby with low birth- weight,fetal demise, or congenital anomaly compared to the control group. Women with treated hypothyroid disease were more likely to have chronic hypertension (2.3% vs. 1.2%, p = 0.03) and had an increased risk of pre-eclampsia (4.3% vs. 2.6%,p= 0.03) compared to women without thyroid disease. CONCLUSION: Women with treated hypothyroid disease are not at higher risk than the general population for adverse neonatal outcomes, but may be at increased risk for pre-eclampsia.

Association of rheumatologic disease with preeclampsia.

OBJECTIVE: To determine whether maternal rheumatologic disease is associated with an increased risk of adverse obstetric or neonatal outcomes. METHODS: Using an institutional database, we identified all women with diagnosed rheumatologic disease (n = 114) who delivered a baby at our institution during a 33-month period. We compared the incidence of adverse obstetric and neonatal outcomes among these women with the incidence among women without rheumatologic diseases (n = 18,534). RESULTS: Women with rheumatologic diseases were more likely to have preeclampsia than women without rheumatologic disease (8.8% versus 2.3%, P <.001) Women with rheumatologic diseases were also at increased risk of preterm delivery (15.2% versus 7.8%, P =.002) and small-for-gestational-age infants (8.0% versus 3.1%, P =.001) compared with women without rheumatologic disease. CONCLUSION: The finding that women with rheumatologic diseases are at increased risk of adverse obstetric outcomes suggests a need for heightened clinical vigilance and further research into the common pathophysiologic correlates. LEVEL OF EVIDENCE: II-2

Maternal age and other predictors of newborn blood pressure.

OBJECTIVE: To investigate perinatal predictors of newborn blood pressure. STUDY DESIGN: Among 1059 mothers and their newborn infants participating in Project Viva, a US cohort study of pregnant women and their offspring, we obtained five systolic blood pressure readings on a single occasion in the first few days of life. Using multivariate linear regression models, we examined the extent to which maternal age and other pre- and perinatal factors predicted newborn blood pressure level. RESULTS: Mean (SD) maternal age was 32.0 (5.2) years, and mean (SD) newborn systolic blood pressure was 72.6 (9.0) mm Hg. A multivariate model showed that for each 5-year increase in maternal age, newborn systolic blood pressure was 0.8 mm Hg higher (95% CI, 0.2, 1.4). In addition to maternal age, independent predictors of newborn blood pressure included maternal third trimester blood pressure (0.9 mm Hg [95% CI, 0.2, 1.6] for each increment in maternal blood pressure); infant age at which we measured blood pressure (2.4 mm Hg [95% CI 1.7, 3.0] for each additional day of life); and birth weight (2.9 mm Hg [95% CI, 1.6, 4.2] per kg). CONCLUSIONS: Higher maternal age, maternal blood pressure, and birth weight were associated with higher newborn systolic blood pressure. Whereas blood pressure later in childhood predicts adult hypertension and its consequences, newborn blood pressure may represent different phenomena, such as pre- and perinatal influences on cardiac structure and function.

Perinatal outcome after preterm premature rupture of membranes with in situ cervical cerclage.

OBJECTIVE: The presence of a cervical cerclage at the time of preterm premature rupture of membranes (pPROM) could promote clinically evident infection and adverse pregnancy outcome. This cohort study examines whether the presence of cerclage at the time of pPROM is associated with increased maternal or neonatal inflammatory morbidity. STUDY DESIGN: All singleton pregnancies with cerclage and pPROM between 24.0 and 33.9 weeks' gestation at our institution (January 1985-December 1997) were reviewed. Controls (pPROM without cerclage) were matched 2.5:1 by year of presentation. Outcome measures suggest clinical evidence of an infectious response and include maternal admission white blood cell count, time to onset of preterm labor, clinical chorioamnionitis, postpartum fever, neonatal white-matter disease (intraventricular hemorrhage or periventricular leukomalacia) at less than 33 weeks, neonatal sepsis, and neonatal death. RESULTS: One hundred fourteen cases of pPROM and cerclage were matched with 288 controls. The study had power (alpha =.05, power = 0.8) to detect a two-fold difference in incidence of adverse neonatal outcome. Among the mothers, the incidence of clinical chorioamnionitis (14.0% vs 18.8%, P =.26), uterine activity at admission (33.3% vs 32.2%, P =.44), maternal postpartum fever (7.9% vs 7.6%, P =.93) in cerclage versus no cerclage were equivalent. Among the neonates, the incidence of neonatal white- matter disease (15.3% vs 13.7%, P =.75), neonatal sepsis (9.1% vs 6.0%, P =.21), and neonatal death were similar. CONCLUSION: Rates of maternal and neonatal morbidity were similar between both groups. The close overall similarity between the groups strongly suggest clinically insignificant differences between the two groups. These data indicate that a cervical cerclage at the time of pPROM less than 34 weeks does not adversely affect pregnancy outcome.

Differences in systemic opioid use do not explain increased fever incidence in parturients receiving epidural analgesia.

BACKGROUND: It has been hypothesized that an increased incidence of fever in patients receiving epidural analgesia might result not from epidural per se, but rather from the antipyretic effect of opioids preferentially administered to women in the no-epidural group. If this were the case, then one would expect the incidence of fever in parturients who did not receive systemic opioids to be independent of whether they received epidural analgesia. METHODS: Using a cohort study design, the authors evaluated the records of 1,233 nulliparous patients whose labor analgesia was managed with (1) no medication (N = 170); (2) 10 mg intravenous systemic nalbuphine plus 10 mg intramuscular every 3 to 4 h as required (N = 327); (3) epidural analgesia with continuous infusion of 0.125% bupivacaine with 2 microg/ml fentanyl (N = 278); or (4) patients who received both systemic nalbuphine and epidural analgesia (N = 458). Fever was diagnosed if the maximum temperature during labor exceeded 100.4 degrees F (38 degrees C). RESULTS: The incidence of fever did not differ according to nalbuphine administration for women not receiving epidural analgesia (1% no nalbuphine, 0.3% with nalbuphine, P = 0.27) or for women receiving epidural analgesia (17% no nalbuphine, 17% with nalbuphine, P = 1.0). However, the incidence of fever differed significantly between patients who received no analgesia as compared to those who received epidural analgesia alone (1% vs. 17%, P = 10(-6)). Controlling for confounding did not alter these associations. CONCLUSIONS: Our findings suggest that an antipyretic effect of nalbuphine in patients who do not receive an epidural does not explain the greater incidence of fever observed in women who receive epidural analgesia for labor.