Jamie L. Morgan

Pregnancy outcomes after antepartum tetanus, diphtheria, and acellular pertussis vaccination.

OBJECTIVE: To evaluate pregnancy outcomes of women who received tetanus, diphtheria, and acellular pertussis (Tdap) vaccination at or after 32 weeks of gestation. Outcomes from consecutive pregnancies during which the mother received Tdap were also analyzed. METHODS: In a retrospective cohort study at a single institution, we compared pregnancy outcomes between those who accepted or declined Tdap at 32 weeks of gestation. Additionally, women who received Tdap vaccination in this and a prior pregnancy in the past 5 years were compared with multiparous women who only received Tdap in this pregnancy. RESULTS: Since 2013, 7,378 women who were offered the Tdap vaccine antenatally delivered at our institution: 7,152 accepted (97%). There was no difference in stillbirths, major malformations, chorioamnionitis, 5-minute Apgar score, or cord blood pH. Neonatal complications including ventilation requirement, sepsis, intraventricular hemorrhage, and neonatal death were also similar. However, preterm birth rates at 36 weeks of gestation or less (6% compared with 12%, P<.001), incidence of small for gestational age (10% compared with 15%, P=.03), and length of neonatal hospitalization (3.9 compared with 4.7 days, P<.001) were all significantly increased in the unvaccinated cohort. No difference in neonatal outcomes was noted between women who were administered at least two Tdap vaccines in the past 5 years (n=1,229) and those who received only a single dose (n=4,159). CONCLUSION: No adverse pregnancy outcomes were identified in association with antepartum Tdap vaccination. This remained true in women receiving more than one Tdap vaccine in a 5-year timeframe. This may be the result of a type II error. LEVEL OF EVIDENCE: II

Association of a Best-Practice Alert and Prenatal Administration With Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccination Rates.

OBJECTIVE: To evaluate how implementation of a best-practice alert, a reminder of clinical guidelines within the electronic medical record, in combination with the recommended change in immunization timing from postpartum to antepartum, affected tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) rates, and to examine the association of vaccination with local pertussis attack rates. METHODS: A Tdap best-practice alert was introduced into the electronic prenatal charting system in June 2013. The best-practice alert was designed to appear starting at 32 weeks of gestation and to reappear at every subsequent encounter until vaccine acceptance was recorded or delivery occurred. The overall acceptance rate was then compared with postpartum vaccination rates at our institution from the previous year. Records of pertussis cases in children younger than 2 years of age diagnosed since 2012 in Dallas County were also reviewed to correlate local trends with vaccination efforts. RESULTS: Of the 10,201 women offered Tdap during prenatal care, 9,879 (96.8%) ultimately accepted. This is compared with a 48% (5,064 of 10,600) Tdap postpartum immunization rate in the year prior, before introduction of the best-practice alert. The incidence of pertussis among neonates born to mothers who received prenatal care at Parkland Hospital showed a nonsignificant decline from 13 cases per 10,000 deliveries (19 of 14,834, 95% confidence interval [CI] 7–19) between January 2012 and May 2013 to seven per 10,000 deliveries during the study period (eight of 11,788, 95% CI 2–11, P=.174). CONCLUSION: The use of a best-practice alert, in concert with the recommended change in timing of maternal vaccination from postpartum to antepartum, was associated with an increase in the Tdap immunization rate to 97%. LEVEL OF EVIDENCE: II

Metabolic Acidemia in Live Births at 35 Weeks of Gestation or Greater.

OBJECTIVE: To estimate the incidence of metabolic acidemia and assess its association with a variety of obstetric complications in a large cohort of singleton live births at 35 weeks of gestation or greater. METHODS: We analyzed obstetric complications and neonatal outcomes associated with metabolic acidemia in singleton newborns delivered at 35 weeks of gestation or greater. Metabolic acidemia was identified as an umbilical artery pH of less than 7.0 and a base deficit of 12 mmol/L or greater from umbilical cord blood gas analyses performed immediately after delivery. The primary outcome of interest was seizures in the immediate newborn period. RESULTS: Between January 1, 1988, and December 31, 2013, a total of 1,265 (3.9/1,000, 95% confidence interval [CI] 3.7–4.1) neonates were identified with metabolic acidemia among 323,027 live births with cord gas analysis. Virtually every recorded obstetric complication was significantly associated with metabolic acidemia. All measures of neonatal morbidity except necrotizing enterocolitis were also significantly increased in the presence of metabolic acidemia. Seizures occurred in 367 of 323,027 (1.1/1,000, 95% CI 1.0–1.3) neonates. Only 19.1% (95% CI 15.2–23.5%) occurred in those with metabolic acidemia. Among the 1,265 with metabolic acidemia, 70 were diagnosed with neonatal seizures, for a prevalence of 5.5% (95% CI 4.3–6.9) in the acidotic group. CONCLUSION: Neonatal acidemia at birth is rare in deliveries occurring at or after 35 weeks of gestation. Seizures occur in less than one in 10 newborns with metabolic acidemia. Approximately 80% of seizures in neonates at this gestational age occur in nonacidemic neonates. LEVEL OF EVIDENCE: III

Impact of metabolic acidemia at birth on neonatal outcomes in infants born before 34 weeks’ gestation

Abstract Purpose: To examine prematurity-associated neonatal outcomes in early preterm infants with metabolic acidemia compared to those without such acidemia. Methods: We performed a retrospective cohort analysis to assess the impact of metabolic acidemia on prematurity-associated complications in a large cohort of singleton live-born infants with complete umbilical cord gas analyses delivered between 24 0/7 and 33 6/7 weeks. Metabolic acidemia was defined as an umbilical artery pH less than 7.0 plus a base deficit of 12 mmol/L or greater. Outcomes were adjusted for gestational age using logistic regression. Results: Between 1 January 1988 and 31 December 2014, 6970 singleton early preterm infants were delivered at our hospital, of which 126 (1.8%) had metabolic acidemia. Neonatal mortality as well as prematurity-associated morbidities were significantly increased in the presence of metabolic acidemia. Included were ventilator requirement (73% versus 36%, p < 0.001), grade 3/4 intraventricular hemorrhage (10% versus 4%, p < 0.001), periventricular leukomalacia (5% versus 2%, p = 0.036), and neonatal death (13% versus 4%, p < 0.001). These significant findings persisted after adjustment for gestational age. Conclusion: Metabolic acidemia significantly increases the risks related to prematurity in infants delivered prior to 34 weeks’ gestation.

Frequency and consequences of ventricular hypertrophy in pregnant women with treated chronic hypertension

BACKGROUND: Ventricular hypertrophy is a known sequela of long‐standing chronic hypertension with associated morbidity and mortality. OBJECTIVE: We sought to assess the frequency and importance of left ventricular hypertrophy in gravidas treated for chronic hypertension during pregnancy. STUDY DESIGN: This was a retrospective study of pregnant women with chronic hypertension who were delivered at our hospital from January 2009 through February 2015. All women who were given antihypertensive therapy underwent maternal echocardiography and were managed in a dedicated, high‐risk prenatal clinic. Left ventricular hypertrophy was defined using the criteria of the American Society of Echocardiography as left ventricular mass indexed to maternal body surface area with a value of >95 g/m2. Maternal and infant outcomes were then analyzed according to the presence or absence of left ventricular hypertrophy. RESULTS: Of 253 women who underwent echocardiography, 48 (19%) met criteria for left ventricular hypertrophy. Women in this latter cohort were significantly more likely to be African American (P = .031), but there were no other demographic differences. More than 85% of the entire cohort had a body mass index >30 kg/m2 and a third of all women had class III obesity with a body mass index of >40 kg/m2. Importantly, duration of chronic hypertension (P = .248) and gestational age at time of echocardiography (P = .316) did not differ significantly between the groups. Left ventricular function was preserved in both groups as measured by left ventricular ejection fraction (P = .303). Those with ventricular hypertrophy were at greater risk to be delivered preterm (P = .001), to develop superimposed preeclampsia (P = .028), and to have an infant requiring intensive care (P = .023) when compared with women without ventricular hypertrophy. These findings persisted after adjustment for age, race, and parity. The gestational age at delivery according to measured left ventricular size was also examined and with increasing ventricular mass there was a significant association with the severity of preterm birth (P < .001). CONCLUSION: Left ventricular hypertrophy was identified in 1 in 5 women given antepartum treatment for chronic hypertension. Further analysis showed that these women were at significantly greater risk for superimposed preeclampsia and its attendant perinatal sequelae of preterm birth.

Association of Baseline Proteinuria and Adverse Outcomes in Pregnant Women With Treated Chronic Hypertension.

OBJECTIVE: To assess the importance of baseline proteinuria in women treated for chronic hypertension during pregnancy. METHODS: This retrospective cohort study included women with chronic hypertension who received antihypertensive therapy in the first half of pregnancy and completed urine protein quantification before 20 weeks of gestation. Maternal and neonatal outcomes were analyzed according to the presence or absence of baseline proteinuria, defined as 300 mg or greater per 24 hours identified before 20 weeks of gestation. Frequencies of superimposed preeclampsia, preterm birth, and small-for-gestational-age neonates were further evaluated according to stratified urine protein excretion levels from less than 50 mg to greater than 1,000 mg/24 hours. RESULTS: Between January 2002 and December 2014, a total of 447 women met inclusion criteria. Of these, 56 (13%) had baseline proteinuria. Women with baseline proteinuria were statistically significantly more likely to develop superimposed preeclampsia (79% compared with 49%), deliver preterm (18% compared with 6% 30 weeks of gestation or less, 34% compared with 17% 34 weeks of gestation or less, and 48% compared with 26% less than 37 weeks of gestation), and deliver an small-for-gestational-age neonate (41% compared with 22% less than the 10th percentile, 20% compared with 9% less than the third percentile) when compared with women who did not have proteinuria (all P<.05). Furthermore, the rates of superimposed preeclampsia and small for gestational age were significantly increased as 24-hour protein excretion levels increased across stratified levels (P for trend .002 and .015, respectively). When proteinuria levels less than 300 mg/d were analyzed separately, a significant association was observed for rates of superimposed preeclampsia and preterm birth. CONCLUSION: In pregnant women with treated chronic hypertension, baseline proteinuria was significantly associated with increased rates of preeclampsia, preterm birth, and growth restriction—even at proteinuria values previously considered to be within normal range (less than 300 mg/d).

Blood Pressure Profiles Across Pregnancy in Women with Chronic Hypertension

Objective To examine blood pressure patterns across pregnancy in women with treated chronic hypertension according to the occurrence of severe preeclampsia, growth restriction, and preterm birth <34 weeks. Methods This retrospective descriptive case study included only pregnant women receiving antihypertensive therapy. Using a random effects model, mean arterial pressures were plotted across gestation for women with and without preeclampsia, fetal growth restriction, and preterm birth <34 weeks with differences analyzed for each curve. Results Between January 2002 and December 2014, 447 women met inclusion criteria. Of these women, 65% developed severe preeclampsia, 24% delivered an infant weighing <10th percentile, and 15% had a preterm birth <34 weeks. Women diagnosed with either preeclampsia (23.3 vs 26.4 weeks; mean difference, 3.1 weeks; 95% confidence interval [CI], 2.3-4.3), fetal growth restriction (23.5 vs 24.9 weeks; mean difference, 1.4 weeks; 95% CI, 0.2-2.6), or preterm birth (19.8 vs 24.9 weeks; mean difference, 5.1 weeks; 95% CI, 3.7-6.9) reached a blood pressure nadir at a significantly earlier gestational age than those who did not. Conclusion For pregnant women with treated chronic hypertension, blood pressure patterns differ significantly in those who develop severe preeclampsia, fetal growth restriction, and preterm birth <34 weeks.

Pharmacokinetics of amlodipine besylate at delivery and during lactation

BACKGROUND Amlodipine is rarely used in the treatment of pregnant hypertensive women due to limited pharmacokinetic data during pregnancy and the postpartum period. OBJECTIVE To evaluate the pharmacokinetics of amlodipine besylate in the peri-partum period including quantities of placental passage, breast milk excretion and infant exposure. STUDY DESIGN This was a prospective study of pregnant women who were prescribed 5 mg of amlodipine daily for treatment of chronic hypertension and delivered at term. Cord and maternal blood samples were collected at delivery. On postpartum day 2, six paired maternal plasma and breast milk samples were obtained at 4, 6, 8, 12, 15 and 24 h following amlodipine dosing. Infant plasma samples were collected 24-48 h after delivery. All samples were analyzed for amlodipine concentration. A one compartment, first-order model was used to calculate pharmacokinetic estimates for maternal plasma. RESULTS Of the 16 patients enrolled in the study, 11 had cord blood and maternal serum collected at delivery, of which only 6 produced sufficient breast milk for sampling. Amlodipine was detected in infant cord blood plasma with a mean concentration of 0.49 ± 0.29 ng/mL compared to mean maternal serum level of 1.27 ± 0.84 ng/mL. Amlodipine concentrations in both in breast milk and infant plasma were undetectable at the lower limit of assay detection (<0.1 ng/mL). In the immediate postpartum period, the amlodipine elimination half-life was 13.7 ± 4.9 h, the area under the curve was 53.4 ± 19.8 ng*h/mL and the peak concentration was 2.0 ± 1.0 ng/mL. CONCLUSIONS Amlodipine does cross the placenta in measurable quantities, but is not detected in breast milk or infant plasma at 24-48 h of life indicating that it is likely safe to use during the peripartum period.

Perinatal outcomes associated with abnormal cardiac remodeling in women with treated chronic hypertension

BACKGROUND Adverse maternal outcomes associated with chronic hypertension include accelerated hypertension and resultant target organ damage. One example is long‐standing hypertension leading to maternal cardiac dysfunction. Our group has previously identified that features of such injury manifest as cardiac remodeling with left ventricular hypertrophy. Moreover, these features of cardiac remodeling identified in women with chronic hypertension during pregnancy were associated with adverse perinatal outcomes. Recent definitions of maternal cardiac remodeling using echocardiography have been expanded to include measurements of wall thickness. We hypothesized that these new features characterizing cardiac remodeling in women with chronic hypertension may also be associated with adverse perinatal outcomes. OBJECTIVE There were 3 aims in this study of women with treated chronic hypertension during pregnancy: to (1) apply the updated definitions of maternal cardiac remodeling; (2) elucidate whether these features of cardiac remodeling were associated with adverse perinatal outcomes; and (3) determine which, if any, of the newly defined cardiac remodeling strata were most damaging when compared to women with normal cardiac geometry. STUDY DESIGN This was a retrospective study of women with treated chronic hypertension during pregnancy delivered from January 2009 through January 2016. Cardiac remodeling was categorized by left ventricular mass index and relative wall thickness into 4 groups determined using the 2015 American Society of Echocardiography guidelines: normal geometry, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. Perinatal outcomes were analyzed according to each category of cardiac remodeling compared with outcomes in women with normal geometry. RESULTS A total of 314 women with treated chronic hypertension underwent echocardiography at a mean gestational age of 17.9 weeks. There were no differences between maternal age (P = .896), habitus (P = .36), or duration of chronic hypertension (P = .212) among the 4 groups. Abnormal cardiac remodeling was found in 51% and was significantly associated with increased rates of superimposed preeclampsia (P = .015), preterm birth (P < .001), and neonatal intensive care admission (P = .003). These outcomes reached the greatest significance when comparisons were made between eccentric hypertrophy and normal geometry. CONCLUSION Using current American Society of Echocardiography guidelines, 51% of women with treated chronic hypertension during pregnancy have some degree of abnormal cardiac remodeling. Any suggestion of maternal cardiac remodeling, regardless of subtype, was associated with increased risks for superimposed preeclampsia and preterm birth with its resultant perinatal sequelae. Eccentric ventricular hypertrophy, previously thought to mimic exercise physiology, appears to be the most associated with adverse perinatal outcomes. Despite evidence of cardiac remodeling, ejection fraction was preserved.