Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Benefits and harms of perioperative high fraction inspired oxygen for surgical site infection prevention: a protocol for a systematic review and meta-analysis of individual patient data of randomised controlled trials.

INTRODUCTION: The use of high fraction of inspired oxygen (FiO2) intraoperatively for the prevention of surgical site infection (SSI) remains controversial. Promising results of early randomised controlled trials (RCT) have been replicated with varying success and subsequent meta-analysis are equivocal. Recent advancements in perioperative care, including the increased use of laparoscopic surgery and pneumoperitoneum and shifts in fluid and temperature management, can affect peripheral oxygen delivery and may explain the inconsistency in reproducibility. However, the published data provides insufficient detail on the participant level to test these hypotheses. The purpose of this individual participant data meta-analysis is to assess the described benefits and harms of intraoperative high FiO2compared with regular (0.21-0.40) FiO2 and its potential effect modifiers. METHODS AND ANALYSIS: Two reviewers will search medical databases and online trial registries, including MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and WHO regional databases, for randomised and quasi-RCT comparing the effect of intraoperative high FiO2 (0.60-1.00) to regular FiO2 (0.21-0.40) on SSI within 90 days after surgery in adult patients. Secondary outcome will be all-cause mortality within the longest available follow-up. Investigators of the identified trials will be invited to collaborate. Data will be analysed with the one-step approach using the generalised linear mixed model framework and the statistical model appropriate for the type of outcome being analysed (logistic and cox regression, respectively), with a random treatment effect term to account for the clustering of patients within studies. The bias will be assessed using the Cochrane risk-of-bias tool for randomised trials V.2 and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. Prespecified subgroup analyses include use of mechanical ventilation, nitrous oxide, preoperative antibiotic prophylaxis, temperature (<35°C), fluid supplementation (<15 mL/kg/hour) and procedure duration (>2.5 hour). ETHICS AND DISSEMINATION: Ethics approval is not required. Investigators will deidentify individual participant data before it is shared. The results will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42018090261.

Expansion of B4GALT7 linkeropathy phenotype to include perinatal lethal skeletal dysplasia.

Proteoglycans have a core polypeptide connected to glycosaminoglycans (GAGs) via a common tetrasaccharide linker region. Defects in enzymes that synthesize the linker result in a group of autosomal recessive conditions called "linkeropathies". Disease manifests with skeletal and connective tissue features, including short stature, hyperextensible skin, and joint hypermobility. We report a family with three affected pregnancies showing short limbs, cystic hygroma, and perinatal death. Two spontaneously aborted; one survived 1 day after term delivery, and had short limbs, bell-shaped thorax, 11 ribs, absent thumbs, and cleft palate. Exome sequencing of the proband and one affected fetus identified compound heterozygous missense variants, NM_007255.3: c.808C>T (p.(Arg270Cys)) and NM_007255.3: c.398A>G (p.(Gln133Arg)), in B4GALT7, a gene required for GAG linker biosynthesis. Homozygosity for p.(Arg270Cys), associated with partial loss of B4GALT7 function, causes Larsen of Reunion Island syndrome (LRS), however no previous studies have linked p.(Gln133Arg) to disease. The p.(Gln133Arg) and p.(Arg270Cys) variants were transfected into CHO pgsB-618 cells. High protein expression of p.(Gln133Arg) was found, with mislocalization, compared to p.(Arg270Cys) that had a normal Golgi-like pattern. The p.(Gln133Arg) had almost no enzyme activity and little production of heparan sulfate GAGs, while p.(Arg270Cys) only had 17% of wild-type activity. These findings expand the phenotype of B4GALT7-related linkeropathies to include lethal skeletal dysplasia due to more severe loss of function.

Antenatal Betamethasone for Women at Risk for Late Preterm Delivery.

BACKGROUND: Infants who are born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse respiratory and other outcomes than those born at 37 weeks of gestation or later. It is not known whether betamethasone administered to women at risk for late preterm delivery decreases the risks of neonatal morbidities. METHODS: We conducted a multicenter, randomized trial involving women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation who were at high risk for delivery during the late preterm period (up to 36 weeks 6 days). The participants were assigned to receive two injections of betamethasone or matching placebo 24 hours apart. The primary outcome was a neonatal composite of treatment in the first 72 hours (the use of continuous positive airway pressure or high-flow nasal cannula for at least 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygenation, or mechanical ventilation) or stillbirth or neonatal death within 72 hours after delivery. RESULTS: The primary outcome occurred in 165 of 1427 infants (11.6%) in the betamethasone group and 202 of 1400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02). Severe respiratory complications, transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia also occurred significantly less frequently in the betamethasone group. There were no significant between-group differences in the incidence of chorioamnionitis or neonatal sepsis. Neonatal hypoglycemia was more common in the betamethasone group than in the placebo group (24.0% vs. 15.0%; relative risk, 1.60; 95% CI, 1.37 to 1.87; P<0.001). CONCLUSIONS: Administration of betamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications. (Funded by the National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01222247.).

Effect of Tocolytics on Surfactant Secretion When Administered with Betamethasone: An in Vitro Study.

OBJECTIVE: To analyze the amount of surfactant protein (SP)-B and lecithin/sphingomyelin (L/S) ratio in response to betamethasone (BMS) alone as compared with magnesium sulfate (Mg(2+)), indomethacin (Indo), and nifedipine (Nif) with or without BMS. STUDY DESIGN: NCI-H441 human lung cells were grown and distributed into eight plates. BMS and tocolytics were added and the final plates were: control, BMS only, and each tocolytic ± BMS. Cells were stained with SP-B antibodies and relative fluorescence was measured. Lipids were also extracted, identified, and examined for relative densities. The L/S ratio was calculated. RESULTS: Nine independent measurements were obtained for each plate. The protein analysis revealed that among all eight plates, SP-B levels were highest among BMS only. There was a nonsignificant decrease in SP-B in each of the combinations of tocolytics + BMS as compared with BMS only. Compared with BMS only, L/S ratio was decreased in Mg(2+) + BMS (p = 0.041), Indo + BMS (p = 0.042), and Nif + BMS (p = 0.025). CONCLUSION: In our in vitro human lung cell model, SP-B and L/S ratio increased in response to BMS administration alone. The addition of tocolytics to BMS resulted in no increase in L/S ratio and no changes seen in SP-B production compared with BMS alone.

Randomized controlled trial of the effect of 30% versus 80% fraction of inspired oxygen on cesarean delivery surgical site infection.

OBJECTIVE: To determine if supplemental perioperative oxygen will reduce surgical site infection (SSI) following cesarean delivery. METHODS: This is a randomized, controlled trial evaluating SSI following either 30% or 80% fraction of inspired oxygen (FIO2) during and 2 hours after cesarean delivery. Anesthesia providers administered FIO2 via a high-flow oxygen blender. Subjects, surgeons, and wound evaluation teams were blinded. Serial wound evaluations were performed. Data were analyzed using logistic regression models, Fisher exact test, and t test. RESULTS: In all, 179 women were randomized, and 160 subjects were included in the analysis. There were 12/83 (14.5%) SSIs in the control group versus 10/77 (13.0%) in the investigational group (p = 0.82). Caucasian race, increased body mass index, and longer operative time were identified as significant risk factors for infection (p = 0.026, odds ratio 0.283; p = 0.05, odds ratio = 1.058; p = 0.037, odds ratio = 1.038, respectively). CONCLUSION: Perioperative oxygenation with 80% Fio2 is not effective in reducing SSI following cesarean delivery.

A randomized trial of micronized progesterone for the prevention of recurrent preterm birth.

We sought to evaluate the effectiveness of daily oral micronized progesterone (MP) in preventing recurrent spontaneous preterm birth (RSPB) and whether MP increases maternal serum progesterone. We performed a pilot, single-center, randomized, double-blind, placebo-controlled trial in women with a prior preterm birth and current singleton gestation at 16 to 20 weeks ( N = 33). The primary outcome was the rate of RSPB. Subjects were given either daily MP (400 mg) or placebo from 16 to 34 weeks. Serum progesterone was obtained at enrollment and in the late second/early third trimester. Pregnancy outcome data were collected. RSPB occurred in 5/19 (26.3%) in the MP group versus 8/14 (57.1%) in placebo group ( P = 0.15). The mean age at delivery was 37.0 ± 2.7 weeks for the MP group versus 35.9 ± 2.6 weeks for the placebo ( P = 0.3). Mean serum progesterone at 28 weeks was 122.6 ± 61.8 pg/mL for MP group versus 90.1 ± 38.7 pg/mL for placebo ( P = 0.19). MP was associated with a trend toward a reduction in RSPB and an increase in the maternal serum progesterone. Although the primary outcome in this pilot study did not reach statistical significance, the results suggest a favorable trend meriting further investigation.

Maternal group B streptococcal (GBS) genital tract colonization at term in women who have asymptomatic GBS bacteriuria.

OBJECTIVE: To determine the rate of positive group B streptococcus (GBS) cultures at 35-37 weeks gestation in women who have first trimester asymptomatic GBS bacteriuria. METHODS: Pregnant women with asymptomatic first trimester GBS bacteriuria had genital cultures for GBS performed at 35-37 weeks gestational age. Serotyping was performed by the standard Lancefield capillary precipitin method. RESULTS: Fifty-three women with positive urine cultures had genital cultures performed at 35-37 weeks. Sixteen of the 53 (30.2%; 95% confidence interval: 18.4-44.3%) third trimester vaginal cultures were positive for GBS. Five of eight (63%) of the women with typable urine serotypes had the same typable serotype in the third trimester genital culture. CONCLUSION: Genital tract cultures at 35-37 weeks for GBS correlate poorly with first trimester asymptomatic GBS bacteriuria. Recommendations for GBS prophylaxis in labor in women who have first trimester asymptomatic GBS bacteriuria should be investigated further and reconsidered.

Cervicovaginal fetal fibronectin levels in women with preeclampsia.

OBJECTIVE: To estimate the mean levels of fetal fibronectin in cervicovaginal secretions of women with preeclampsia and compare them with levels in normotensive controls. METHODS: Cervicovaginal swabs were obtained before digital examination from women who presented to labor and delivery for evaluation of preeclampsia and compared with fetal fibronectin levels from a group of control subjects with a similar gestational age. Fetal fibronectin was assayed by a specific enzyme-linked immunoassay. A concentration greater than 50 ng/mL was considered a positive result. RESULTS: Forty women with preeclampsia (17 mild and 23 severe) and 31 normotensive women were analyzed. The control group had 9.7% positive fetal fibronectins, whereas the preeclampsia group had 15% positive, P =.72, with 80% power to detect a 22% difference. The majority of the quantitative values in both groups were less than 20 ng/mL. There was not a significant difference between the two groups in quantitative cervicovaginal fetal fibronectin, P =.72, nor was there a difference between the women with severe preeclampsia and the controls, P = 1.0, or between the nulliparous women with preeclampsia versus the nulliparous controls, P =.3. CONCLUSION: Fetal fibronectin is not elevated in cervicovaginal secretions of women with preeclampsia.