Antibiotic Treatment for Well-Appearing Infants Born at ≥35 Weeks' Gestation to Mothers with Chorioamnionitis Before and After Implementation of Neonatal Early-Onset Sepsis Calculator.

Purpose: Our quality improvement study aimed to determine whether application of a neonatal early-onset sepsis calculator (NSC) among well-appearing infants born at ≥35 weeks' gestation to mothers with chorioamnionitis decreases the number of lab evaluations (LEs) and antibiotic treatments (Abxs) without missing early-onset sepsis. Methods: We compared 2 years (January 1, 2019-January 3, 2021) of data from a historical-control group before implementation of the NSC to 1 year (January 4, 2021-December 31, 2021) of data from a calculator group after implementation of the NSC to evaluate whether LE and Abx decreased following implementation of the NSC on January 4, 2021. A P-value of <0.05 was considered statistically significant for the chi-squared test, Fisher's exact test, Student's t-test, and Mann-Whitney U test used for the analyses. Results: In the historical-control group, 94% of infants received LE and Abx. Retrospective application of the NSC in the historical-control group decreased LE from 94% to 21% and Abx from 94% to 13%. In the calculator group, 14% and 5% of infants received LE and Abx, respectively, and none of the blood culture was positive. Median time from birth to antibiotic initiation was significantly longer (14.5 vs 3.8 hours; P=0.0037) with no increase in median length of stay (2.3 vs 2.4 days; P=0.02) after NSC implementation. No significant difference in neonatal intensive care unit admission was identified between groups (4% vs 1%; P=0.15). Conclusions: There was a significant decrease in LE and Abx among well-appearing infants born at ≥35 weeks' gestation to mothers with chorioamnionitis after implementation of the NSC without missing early-onset sepsis. There was no increase in neonatal intensive care unit admission or length of hospital stay in infants who received antibiotics later after they appeared equivocal or clinically ill in the calculator group. Larger prospective studies that include follow ups are needed to confirm that early-onset sepsis is not missed.

Congenital sodium diarrhoea caused by rare de novo activating guanylate cyclase mutation.

A male infant with prenatal history significant for polyhydramnios requiring multiple amnioreductions with suspicion of small bowel atresia was born at 31 weeks 5 days' gestation with abdominal distension. He underwent three exploratory laparotomies and ileostomy for small bowel obstruction and was found to have fluid-filled intestinal dilatation. Serum and stool chemistries suggested sodium secretory diarrhoea. A rapid whole-exome sequencing confirmed de novo guanylate cyclase mutation variant as a cause for his congenital sodium secretory diarrhoea. He required large volume of fluid and electrolyte replacement along with total parenteral nutrition. Several medications to restore normal sodium homeostasis by targeting molecular mechanisms and pathogenesis described in previous literature failed to decrease stool output and electrolyte loss. He was discharged home at 11 months of age on total parenteral nutrition and weekly iron therapy.

Myocardial performance index in hypertensive disorders of pregnancy: The relationship between blood pressures and angiogenic factors.

OBJECTIVE: To study the association between cardiac function measured by myocardial performance index (MPI), blood pressures and angiogenic factors measured at the time of echocardiography in patients with and without hypertensive disorders of pregnancy (HDP). METHODS: We prospectively studied 189 pregnant women and evaluated whether changes in cardiac function observed on echocardiography were correlated with higher blood pressures and whether higher blood pressures were associated with antiangiogenic proteins (soluble fms-like tyrosine kinase, sFlt1; soluble endoglin, sEng). Comprehensive echocardiograms, including measurement of MPI, were performed on all patients. sFlt1 and sEng levels were measured using enzyme-linked immunosorbent assay. RESULTS: Overall, 189 patients were divided into tertiles based on mean arterial pressure (MAP). The MPI was worst in tertile 3 (0.50 ± 0.15) compared to tertile 1 (0.42 ± 0.10), p = 0.0004. sFlt1 (pg/ml) and sEng (ng/ml) were highest in tertile 3 compared to tertile 1: 15055.37 vs. 1623.01 and 33.06 vs. 8.15, respectively, with p-value <0.001. In crude multivariate regression analysis, MAP was positively correlated with MPI (r = 0.32, p < 0.001), GLS (r = 0.54, p < 0.001), sFlt1 (r = 0.60, p < 0.001) and sEng (r = 0.61, p < 0.001). After adjustment for confounders, these relationships persisted between MAP and MPI (r = 0.31, p = 0.0003), GLS (r = 0.46, p < 0.001), sFlt1 (r = 0.56, p < 0.001) and sEng (r = 0.58, p < 0.001). CONCLUSION: Mean arterial pressure correlates with worsening cardiac function as measured by MPI and serum levels of angiogenic factors. Further studies are needed to evaluate whether a reduction in blood pressure will reverse changes in MPI or reduce levels of angiogenic proteins seen among women with HDP.

Circulating Antiangiogenic Factors and Myocardial Dysfunction in Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy (HDP) are associated with subclinical changes in cardiac function. Although the mechanism underlying this finding is unknown, elevated levels of soluble antiangiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng) are associated with myocardial dysfunction and may play a role. We hypothesized that these antiangiogenic proteins may contribute to the development of cardiac dysfunction in HDP. We prospectively studied 207 pregnant women with HDP and nonhypertensive controls and evaluated whether changes in global longitudinal strain (GLS) observed on echocardiography is specific for HDP and whether these changes correlate with HDP biomarkers, sFlt1 and sEng. A total of 62 (30%) patients were diagnosed with preeclampsia (group A), 105 (51%) did not have an HDP (group B), and 40 (19%) were diagnosed with chronic or gestational hypertension (group C). Blood was drawn and sFlt1 and sEng levels measured using enzyme-linked immunosorbent assay. Comprehensive echocardiograms, including measurement of GLS, were performed on all patients. Overall, GLS was worse in women in group A (preeclampsia) than those in group B or C. Increasing sFlt1 and sEng levels correlated with worsening GLS (r=0.44 for sFlt1 and r=0.46 for sEng, both P<0.001), which remained significant after multivariable analysis (r=0.18 and r=0.22, both P≤0.01). Increasing levels also correlated with increasing left ventricular mass index, which also remained significant after multivariable analysis (r=0.20 for sFlt1 and 0.19 for sEng, both P=0.01). Elevated circulating levels of antiangiogenic proteins in HDP correlate with and may contribute to myocardial dysfunction as measured by GLS.

Sequential plasma angiogenic factors levels in women with suspected preeclampsia.

BACKGROUND: Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. OBJECTIVE: Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. STUDY DESIGN: We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical Center, Boston, Massachusetts, for evaluation of preeclampsia at less than 37 weeks of gestation. Plasma samples were collected on admission and daily for the first 3 days and then weekly until delivery. Doppler ultrasound was performed on admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms-like tyrosine kinase and placental growth factor were measured on automated platform in a single batch after delivery and in a blinded fashion. Data are presented as median (25th to 75th centile), mean, or proportions as appropriate. RESULTS: During the study period, data from 100 women were analyzed for the study, and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, and lower birthweight and placental weight (all P < .01). These patients had higher soluble fms-like tyrosine kinase and soluble fms-like tyrosine kinase/placental growth factor ratio on admission and continued to have an increase in levels throughout hospital course. The median (25th to 75th) soluble fms-like tyrosine kinase/placental growth factor ratio among patients with adverse outcomes was 205.9 (72.5, 453.1) versus 47.5 (9.7, 87.0) among women without adverse outcomes (P < .001). The median (25th to 75th) absolute change per day in soluble fms-like tyrosine kinase levels (pg/mL) was 491.0 pg/mL (120.3, 1587.2) among women with adverse outcomes versus 81.3 pg/mL (-177.9, 449.0) among women without adverse outcomes (P = .01). Similarly the absolute change per day for soluble fms-like tyrosine kinase/placental growth factor ratio was 15.1 (1.8, 58.1) versus 2.7 (-0.6, 8.3) between the two groups (P = .004). The mean (range) days from admission to delivery was 6 (0-35) among subjects with soluble fms-like tyrosine kinase/placental growth factor ratio ≥85 and 14 (0-39) below a ratio of 85 (P < .001). The positive predictive value for plasma soluble fms-like tyrosine kinase/placental growth factor ratio ≥85 at admission for indicated delivery within 2 weeks was 91% (83-99%). Admission plasma soluble fms-like tyrosine kinase/placental growth factor ratio positively correlated with pre-delivery uterine artery resistive index (r = 0.35; P = .004). CONCLUSION: Among women admitted for evaluation of preeclampsia, women at risk for adverse pregnancy outcomes have higher soluble fms-like tyrosine kinase/placental growth factor ratio on admission, which continued to rise until delivery. Women with high soluble fms-like tyrosine kinase/placental growth factor ratios delivered sooner than women with low soluble fms-like tyrosine kinase/placental growth factor levels. These data support the hypothesis that targeting angiogenic imbalance in preeclampsia may lead to prolongation of pregnancy.

Epidemiology and Mechanisms of De Novo and Persistent Hypertension in the Postpartum Period.

BACKGROUND: The pathophysiology of hypertension in the immediate postpartum period is unclear. METHODS AND RESULTS: We studied 988 consecutive women admitted to a tertiary medical center for cesarean section of a singleton pregnancy. The angiogenic factors soluble fms-like tyrosine kinase 1 and placental growth factor, both biomarkers associated with preeclampsia, were measured on antepartum blood samples. We then performed multivariable analyses to determine factors associated with the risk of developing postpartum hypertension. Of the 988 women, 184 women (18.6%) developed postpartum hypertension. Of the 184 women, 77 developed de novo hypertension in the postpartum period, and the remainder had a hypertensive disorder of pregnancy in the antepartum period. A higher body mass index and history of diabetes mellitus were associated with the development of postpartum hypertension. The antepartum ratio of soluble fms-like tyrosine kinase 1 to placental growth factor positively correlated with blood pressures in the postpartum period (highest postpartum systolic blood pressure [r=0.29, P<0.001] and diastolic blood pressure [r=0.28, P<0.001]). Moreover, the highest tertile of the antepartum ratio of soluble fms-like tyrosine kinase 1 to placental growth factor was independently associated with postpartum hypertension (de novo hypertensive group: odds ratio, 2.25; 95% confidence interval, 1.19-4.25; P=0.01; in the persistent hypertensive group: odds ratio, 2.61; 95% confidence interval, 1.12-6.05; P=0.02) in multivariable analysis. Women developing postpartum hypertension had longer hospitalizations than those who remained normotensive (6.5±3.5 versus 5.7±3.4 days; P<0.001). CONCLUSIONS: Hypertension in the postpartum period is relatively common and is associated with prolonged hospitalization. Women with postpartum hypertension have clinical risk factors and an antepartum plasma angiogenic profile similar to those found in women with preeclampsia. These data suggest that women with postpartum hypertension may represent a group of women with subclinical or unresolved preeclampsia.