Obesity and Neonatal Cord Blood Gas Results at Cesarean: Effect of Intraoperative Blood Pressure.

Objective Our aims were to evaluate whether there is an inverse association between body mass index (BMI) and umbilical artery pH and to investigate the contribution of intraoperative hypotension on the umbilical artery pH. Study Design We conducted a retrospective cohort study of all women with a nonanomalous singleton at 37 to 41 weeks who underwent a scheduled cesarean delivery under spinal anesthesia at our facility from January 2006 to March 2012. The primary outcome was the proportion of patients in each BMI category with arterial cord pH < 7.10. Intraoperative blood pressure data were compared across BMI categories. Results In total, 717 mother-infant pairs met enrollment criteria. Mean arterial pH was significantly lower in women with elevated BMI (p = 0.014), notably with BMI ≥ 40 kg/m2. Baseline blood pressure increased linearly with increasing BMI (p < 0.001), however, so did the maximum drop in all blood pressure parameters (p < 0.001). After adjusting for potential confounders, including blood pressure, there was no longer an association between cord pH and BMI (p = 0.72). Conclusion For women undergoing a scheduled cesarean delivery under spinal anesthesia, umbilical artery pH is lower in women with BMI ≥40 kg/m2. Relative hypotension after spinal anesthesia is more pronounced with increasing BMI and may explain this effect.

Alterations in expression of imprinted genes from the H19/IGF2 loci in a multigenerational model of intrauterine growth restriction (IUGR).

BACKGROUND: The H19/IGF2 imprinted loci have attracted recent attention because of their role in cellular differentiation and proliferation, heritable gene regulation, and in utero or early postnatal growth and development. Expression from the imprinted H19/IGF2 locus involves a complex interplay of 3 means of epigenetic regulation: proper establishment of DNA methylation, promoter occupancy of CTCF, and expression of microRNA-675. We have demonstrated previously in a multigenerational rat model of intrauterine growth restriction the epigenetic heritability of adult metabolic syndrome in a F2 generation. We have further demonstrated abrogation of the F2 adult metabolic syndrome phenotype with essential nutrient supplementation of intermediates along the 1-carbon pathway and shown that alterations in the metabolome precede the adult onset of metabolic syndrome. The upstream molecular and epigenomic mediators underlying these observations, however, have yet to be elucidated fully. OBJECTIVE: In the current study, we sought to characterize the impact of the intrauterine growth-restricted lineage and essential nutrient supplementation on both levels and molecular mediators of H19 and IGF2 gene expression in the F2 generation. STUDY DESIGN: F2 intrauterine growth-restricted and sham lineages were obtained by exposing P1 (grandmaternal) pregnant dams to bilateral uterine artery ligation or sham surgery at gestational day 19.5. F1 pups were allocated to the essential nutrient supplemented or control diet at postnatal day 21, and bred at 6-7 weeks of age. Hepatic tissues from the resultant F2 offspring at birth and at weaning (day 21) were obtained. Bisulfite modification and sequencing was employed for methylation analysis. H19 and IGF2 expression was measured by quantitative polymerase chain reaction. Promoter occupancy was quantified by the use of chromatin immunoprecipitation, or ChIP, against CTCF insulator proteins. RESULTS: Growth-restricted F2 on control diet demonstrated significant down-regulation in H19 expression compared with sham lineage (0.7831 vs 1.287; P < .05); however, essential nutrient supplementation diet abrogates this difference (4.995 vs 5.100; P > .05). Conversely, Igf2 was up-regulated by essential nutrient supplemented diet on the sham lineage (2.0 fold, P = .01), an effect that was not observed in the growth restricted offspring. A significant differential methylation was observed in the promoter region of region H19 among the intrauterine growth-restricted lineage (18% vs 25%; P < .05) on a control diet, whereas the essential nutrient supplemented diet was alternately associated with hypermethylation in both lineages (sham: 50%; intrauterine growth restriction: 84%, P < .05). Consistent with essential nutrient supplementation impacting the epigenome, a decrease of CTCF promoter occupancy was observed in CTCF4 of the growth restricted lineage (2.45% vs 0.56%; P < .05) on the control diet, an effect that was repressed with essential nutrient supplementation. CONCLUSION: Heritable growth restriction is associated with changes in H19 gene expression; these changes are reversible with diet supplementation to favorably impact adult metabolic syndrome.

Is low-dose aspirin therapy to prevent preeclampsia more efficacious in non-obese women or when initiated early in pregnancy?

OBJECTIVE: Late timing of intervention and maternal obesity are potential explanations for the modest effect of aspirin for preeclampsia prevention. We explored whether low-dose aspirin (LDA) is more effective in women at increased risk when initiated before 16 weeks' gestation or given to non-obese women. METHODS: Secondary analysis of a trial to evaluate LDA (60 mg/d) for preeclampsia prevention in high-risk women. Participants were randomized to LDA or placebo between 13 and 26 weeks. We stratified the effect of LDA on preeclampsia by (a) timing of randomization (< 16 or ≥ 16 weeks gestation) and (b) body mass index (BMI) class (non-obese and obese). The Breslow-Day test for homogeneity was used to assess for variations in effect of LDA across gestational age and BMI groups. RESULTS: Of 2503 women, 461 (18.4%) initiated LDA < 16 weeks. LDA effect was not better when initiated < 16 weeks (RR: 0.93, 95% CI: 0.67-1.31) versus ≥ 16 weeks (RR: 0.90, 95% CI: 0.75-1.08), (p value for interaction = 0.87). Similarly, LDA effect was not better in non-obese (RR: 0.91, 95% CI: 0.7-1.13) versus obese women (RR: 0.89, 95% CI: 0.7-1.13), (p value for interaction = 0.85). CONCLUSION: LDA for preeclampsia prevention was not more effective when initiated < 16 weeks or used in non-obese women at risk for preeclampsia. No particular subgroup of women was more or less likely to benefit from LDA therapy.

Low-dose aspirin, smoking status, and the risk of spontaneous preterm birth.

OBJECTIVE: We evaluated the relationship between aspirin supplementation and perinatal outcomes for potential effect modification by smoking status. STUDY DESIGN: A secondary analysis of two multicenter trials for which prophylactic aspirin supplementation was given to either low- or high-risk women for prevention of preeclampsia (PE). We examined the effect of aspirin by smoking status using the Breslow-Day test. Primary outcomes for this analysis were PE and preterm birth (PTB) < 37 weeks. We also examined PTB subtypes, small for gestational age (SGA), and neonatal intensive care unit (NICU) admission. RESULTS: The effect of prenatal aspirin on the risk of PE did not differ by smoking status (relative risk [RR] 95% confidence interval [CI] for smokers; RR 95% CI for nonsmokers) in low-risk (Breslow-Day p = 0.32) or high-risk (RR 95% CI for smokers; RR 95% CI for nonsmokers) (Breslow-Day p = 0.58) women. Among women at low risk for PE, the effect of aspirin supplementation on PTB was not different for nonsmokers (RR 1.00 [95% CI 0.8-1.3]) or smokers (RR 0.80 [95% CI 0.4-1.7]), (Breslow-Day p = 0.54). Aspirin was protective for PTB in nonsmokers (RR 0.80 [95% CI 0.7-0.9]), but not in smokers (RR 1.1 [95% CI 0.9-1.4]) in the high-risk group (Breslow-Day p = 0.03). Aspirin was also associated with increased spontaneous and early PTB and NICU admission in smokers and not nonsmokers in the high-risk group only. CONCLUSION: Aspirin supplementation was associated with worse outcomes related to preterm birth in smokers in a high-risk but not low-risk cohort.

Predicting fetal acidemia using umbilical venous cord gas parameters.

OBJECTIVE: To assess the utility of umbilical cord venous blood gas measures for prediction of umbilical artery pH and base deficit acidemia. METHODS: A retrospective cohort study was conducted of all singletons with valid paired arterial and venous cord gas samples delivered at our institution from January 2006 to March 2012. Fetal acidemia was defined primarily as cord arterial blood gas pH less than 7.0. We also evaluated prediction of acidemia, defined as an arterial base deficit 12 mmol/L or greater. Logistic regression was performed to estimate probabilities of fetal arterial pH and base deficit acidemia given venous blood gas pH or base deficit. Receiver operating characteristic curves were derived to determine predictive ability. Venous blood gas pH and base deficit cutoffs associated with 1% or less, 5%, 10%, and 50% probability of fetal acidemia were identified. RESULTS: Of 23,506 births, 11,455 (49%) met criteria for inclusion. The frequency of arterial blood gas pH less than 7.0 was 127 (1.1%); arterial blood gas base deficit 12 mmol/L or greater was 245 (2.1%). Venous blood gas pH (area under the curve [AUC] 0.949, 95% confidence interval [CI] 0.920-0.979; P<.001) and base deficit (AUC 0.969, 95% CI 0.954-0.983; P<.001) were predictors of acidemia based on arterial blood gas pH and base deficit, respectively. Venous blood gas pH cutoffs associated with 1% or less, 5%, or 10% probabilities of arterial blood gas pH less than 7.0 were 7.23, 7.17, and 7.14, respectively. Venous blood gas base deficit values associated with similar probabilities for base deficit 12 mmol/L or greater were 6.3 or less, 8.2 or less, and 9.0 mmol/L or less. For prediction of arterial blood gas pH, adjusting venous blood gas pH for base deficit increased the AUC (0.961, 95% CI 0.938-0.984). Prediction of arterial blood gas base deficit by venous blood gas base deficit was unchanged by adjustment for pH (AUC 0.969, 95% CI 0.955-0.984). CONCLUSION: We demonstrate that venous blood gas parameters are powerful predictors of arterial blood gas pH and base deficit and can be used to predict the likelihood of fetal acidemia when the cord arterial blood gas is not available.

Laboratory abnormalities in pregnancy-associated hypertension: frequency and association with pregnancy outcomes.

OBJECTIVE: To estimate the frequency of abnormal laboratory test results in pregnancy-associated hypertension and the relationship with pregnancy outcomes. METHODS: This was a secondary analysis of a multicenter trial of vitamin C and E for prevention of pregnancy-associated hypertension in low-risk nulliparous women. Laboratory abnormalities included: platelets less than 100,000/mm, aspartate aminotransferase 100 units/L or greater, creatinine 1.5 mg/dL or greater, lactate dehydrogenase 600 units/L or greater, total bilirubin 1.2 mg/dL or greater, or evidence of hemolysis on peripheral smear. Mild pregnancy-associated hypertension was defined as blood pressure 140-159/90-109 mm Hg. Severe pregnancy-associated hypertension was defined as persistent blood pressure 160/110 mm Hg or greater, acute antihypertensive treatment, or any blood pressure elevation associated with clinical signs of end-organ dysfunction (one or more of headache, epigastric pain, blurred vision, pulmonary edema, eclampsia, or oliguria). Pregnancy outcomes were compared across four groups: I, mild hypertension alone; II, mild hypertension+abnormal laboratory values; III, severe pregnancy-associated hypertension alone; and IV, severe pregnancy-associated hypertension+abnormal laboratory values. RESULTS: Of 9,969 women, 2,752 (27.9%) developed pregnancy-associated hypertension and of these, laboratory abnormalities occurred in 7.3%. Laboratory abnormalities increased with severity of hypertension: mild hypertension alone (4.9%), severe hypertension alone (8.9%), and mild or severe hypertension with clinical signs of end-organ dysfunction (12.2%) (P for trend<.001). Compared with women with mild hypertension alone, the adjusted odds for the perinatal composite (2-fold to 4.8-fold in Category III-IV), preterm birth (2.1-fold to 7.8-fold in Category II-IV), and other adverse perinatal outcomes increase with disease severity, particularly with laboratory abnormalities and severe clinical signs. CONCLUSION: The frequency of abnormal laboratory values in women with pregnancy-associated hypertension increases with disease severity. Adverse perinatal outcomes increase in the presence of abnormal laboratory values, particularly in those with clinical signs, likely atttributable in part to the decision to deliver early.

Risk of adverse pregnancy outcomes in women with mild chronic hypertension before 20 weeks of gestation.

OBJECTIVE: To evaluate whether blood pressure (BP) less than 140/90 mm Hg is associated with lower risk of adverse pregnancy outcomes in women with mild chronic hypertension. METHODS: This was a secondary analysis of women with chronic hypertension diagnosed before 20 weeks of gestation (either BP 140/90 mm Hg or greater on two occasions at least four hours apart or previously diagnosed and on antihypertensive therapy) enrolled in the Maternal-Fetal Medicine Units Network's High-risk Aspirin preeclampsia prevention trial. Outcomes including a primary composite (perinatal death, severe preeclampsia, placental abruption, and indicated preterm birth less than 35 weeks of gestation) and small for gestational age (SGA) were compared by study preenrollment BP analyzed as a categorical (less than 140/90, 140-150/90-99, or 151-159/100-109 mm Hg) and as a continuous variable. RESULTS: Among 759 women with singleton pregnancy and preenrollment BP less than 160/110 mm Hg, the incidence of the primary composite outcome (10.7%, 19.0%, 30%) and SGA (8.8%, 12.3%, 23.7%) increased with increasing BP category (P values≤.001). The adjusted odds ratio (95% confidence interval) for the primary composite was 2.0 (1.3-3.2) for 140-150/90-99 mm Hg and 3.2 (1.6-6.3) for 151-159/100-109 mm Hg compared with BP less than 140/90 mm Hg. The results for SGA were 1.6 (0.9-2.8) and 3.8 (1.8-7.9), respectively. Models including continuous systolic and diastolic BP revealed increasing adverse outcomes per 5-mm Hg rise in diastolic but not systolic BP: primary composite (19% per 5 mm Hg) and SGA (22% per 5 mm Hg). CONCLUSION: The risks of adverse pregnancy outcomes in women with chronic hypertension are lower with preenrollment BP less than 140/90 mm Hg as compared with higher BP categories and increase with increasing BP. LEVEL OF EVIDENCE: II.

The association of maternal obesity with fetal pH and base deficit at cesarean delivery.

OBJECTIVE: To evaluate the association between maternal body mass index (BMI) and umbilical cord acid-base status at the time of cesarean delivery. METHODS: We conducted a retrospective multicenter cohort study using data from the Cesarean Section Registry of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Women were included if they delivered a live, nonanomalous singleton at 37-41 weeks of gestation by prelabor cesarean under spinal anesthesia. We excluded women with diagnoses that might be associated with uteroplacental insufficiency. Body mass index at delivery was examined both as a continuous and categorical exposure, and acid-base status was based on cord arterial pH and base deficit. RESULTS: There were 5,742 mother-neonate pairs who met criteria for analysis. Among possible confounders (including sociodemographic variables, number of previous uterine incisions, diabetes, hematocrit, neonatal gender, and birth weight), African American race, birth weight, parity, and smoking status were significantly associated with both BMI and acid-base parameters. Adjusted for those four factors, with increasing BMI category (less than 25, 25-29.9, 30-34.9, 35-39.9, and 40 or higher), mean pH decreased from 7.25 to 7.22 (P<.001), proportion with pH less than 7.1 increased from 3.5% to 7.7% (P=.011), mean base deficit increased from 4.01 mmol/L to 4.83 mmol/L (P=.030), and proportion with base deficit of 12 mmol/L or more increased from 0.6% to 4.7% (P=.003). When BMI was analyzed continuously and adjusted for these confounders, for every 10-unit increase in BMI, cord arterial pH decreased by 0.01 (P<.001) and base deficit increased by 0.26 mmol/L (P=.005). CONCLUSION: For women undergoing nonemergent prelabor cesarean delivery under spinal anesthesia, fetal pH declines and base deficit rises as maternal BMI increases. LEVEL OF EVIDENCE: II.

Placental abruption and fetal demise secondary to placental metastases from unknown primary: a case report.

BACKGROUND: Although maternal malignancy is relatively common, maternal metastases to the products of conception remains a rare event. There is no available literature that describes the incidence of placental metastases as a cause of abruption and fetal death. importanc CASE: We present an unusual case of placental abruption and disseminated intravascular coagulation leading to fetal demise secondary to placental metastases of unknown origin. CONCLUSION: In our case placental abruption likely resulted from metastases to the intervillous space.

Selective uptake of influenza vaccine and pregnancy outcomes.

OBJECTIVE: To describe the characteristics of pregnant women who accept the influenza vaccine and evaluate the relationship between vaccination and adverse pregnancy outcomes. METHODS: Retrospective cohort study of women receiving prenatal care during the 2009-2011 influenza seasons. Vaccination status was ascertained through our perinatal record system and clinic vaccination logs. Pregnancy outcomes included a primary composite of miscarriage, fetal demise, preterm birth (PTB) <37 weeks and neonatal demise. Stratification and logistic regression were used to adjust for potential confounders. RESULTS: Of 3104 eligible pregnant women, 1094 (35%) received the influenza vaccine. Women vaccinated were more likely to be older, obese, primiparae, and have medical complications or a prior PTB. In univariable analyses, flu vaccination was associated with increased adverse composite outcome and PTB. After multivariable adjustments, vaccination was no longer associated with adverse outcomes in women with medical complications but remained associated with adverse outcomes among those without known co-morbidity. CONCLUSIONS: Vaccination was associated with an increased adverse composite outcome in pregnant women without identified co-morbidity but not those with co-morbidities. This association is likely due to selection bias, which should be considered in planning of observational studies of the impact of vaccination on pregnancy outcomes.

Management of influenza in pregnancy.

Influenza is a common viral infection during pregnancy associated with increased adverse maternal and perinatal outcomes. Pregnant women represent a unique population with increased risk for influenza morbidity and mortality. Annual immunization is an effective strategy for prevention of influenza. Despite the universal recommendations for influenza vaccination during pregnancy, 50% or less of pregnant U.S. women on average receive the seasonal vaccine annually. Prompt recognition and treatment of infection or postexposure prophylaxis with recommended antiviral medications may prevent complications in both mother and fetus. We review the epidemiology and management of influenza infection in pregnancy.

Tocolytic therapy for acute preterm labor.

The pathophysiology leading to preterm labor is not well understood and often multifactorial; initiating factors include intrauterine infection, inflammation, ischemia, overdistension, and hemorrhage. Given these different potential causes, directing therapy for preterm labor has been difficult and suboptimal. To date, no single drug has been identified as successful in treating all of the underlying mechanisms leading to preterm labor. In addition, the methodology of many of the tocolytic studies is limited by lack of sufficient patient numbers, lack of comparison with a placebo, and inconsistent use of glucocorticoids. The limitations in these individual studies make it difficult to evaluate the efficacy of a single tocolytic by meta-analysis. Despite these limitations, the goals for tocolysis for preterm labor are clear: To complete a course of glucocorticoids and secure the appropriate level of neonatal care for the fetus in the event of preterm delivery. The literature demonstrates that many tocolytic agents inhibit uterine contractility. The decision as to which tocolytic agent should be used as first-line therapy for a patient is based on multiple factors, including gestational age, the patient's medical history, common and severe side effects, and a patient's response to therapy. In a patient at less than 32 weeks gestation, indomethacin may be a reasonable first choice based on its efficacy, ease of administration, and minimal side effects. Concurrent administration of magnesium for neuroprotection may be given. At 32 to 34 weeks, nifedipine may be a reasonable first choice because it does not carry the fetal risks of indomethacin at these later gestational ages, is easy to administer, and has limited side effects relative to beta-mimetics. In an effort to review a commonly faced obstetrical complication, this article has provided a summary of the most commonly used tocolytics, their mechanisms of action, side effects, and clinical data regarding their efficacy.