Are we preventing the primary cesarean delivery at the second stage of labor following ACOG-SMFM new guidelines? Retrospective cohort study.

OBJECTIVE: In 2014, the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal Fetal Medicine (SMFM) published an Obstetric Care Consensus for safe prevention of primary cesarean delivery. We aimed to assess whether these guidelines decreased the primary CD rate during the second stage of labor, in our department. DESIGN, SETTING, AND POPULATION: A retrospective cohort study of all women reaching the second stage of labor, at term, in a single university-affiliated medical center between2010 and 2017. METHODS: We compared maternal and neonatal outcomes over three year's periods:-pre-guidelines (2010-2013) vs. 2nd period - post-guidelines (2014-2017). THE MAIN OUTCOME MEASURES: CD rate at 2ndstage of labor. RESULTS: The study included 11,464 women. The CD rate in the 2nd stage of labor has increased significantly from 4% to 5.9% in the post-guidelines period (OR 1.48, 95% CI 1.16-1.89, p = .001). After a sub-analysis of specific subgroups, and adjustment for confounders, the increase was solely observed in nulliparous women (aOR 1.418, 95% CI 1.067-1.885, p = .016). Furthermore, increased odds for vaginal operative delivery were observed in the multiparous women in the post-guidelines period (2.7% vs. 4.1%, p = .046). CONCLUSIONS: The implementation of the new ACOG and SMFM guidelines was not associated with a change in the CD rate performed at the 2nd stage of labor in the whole study population. However, there was a rise in the CD rate performed at the 2nd stage in nulliparous women. Furthermore, there was an increase in operative deliveries in the whole study population, especially in multiparous women, without an apparent increase in other immediate adverse neonatal or maternal outcomes.

The impact of nurses' and physicians' shift change on obstetrical outcomes.

PURPOSE: To evaluate the effect around nurses' shift change and on-call physicians' shift change on obstetrical outcomes. METHODS: A retrospective study of women who had an attempt of labor in a single-medical center, January 2006-December 2017. Obstetrical outcomes were compared between the time around nurses' shift change (6:00-8:00, 14:00-16:00, and 22:00-00:00) to the rest of the day, and between the time around on-call physicians' shift change (6:00-8:00, 14:00-16:00) to the rest of the day. RESULTS: 32,861 women were included, 7826 deliveries occurred during nurses' shift-change, and 25,035 deliveries occurred during the rest of the day. The groups had similar general and obstetrical characteristics, with no statistical difference in cesarean delivery rate (10% vs. 9.8%, P = 0.45) (Table 1). Nurses' shift change had no measurable effect on obstetrical outcomes, including induction of labor, preterm labor, 5-min-Apgar score and cord pH value, except PPH which was less likely to occur during nurses' shift change period (3.8% vs. 4.4%, P = 0.045) (Table 2). From 32,861 deliveries, 5155 deliveries occurred during on-call physicians' shift-change, and 27,706 deliveries occurred during the rest of the day. Induction\augmentation of labor and epidural analgesia were less likely to happen during on-call physicians' shift change (34.4% vs. 38%, P < 0.0001, 59.6% vs. 61.8%, P = 0.003, respectively) (Table 3). The two groups had similar obstetrical outcomes, without statistical difference in cesarean delivery rate (10% vs. 9.8%, P = 0.63) (Table 4). Table 1 General and obstetric characteristics of women giving birth during the time of nurses shift change versus during the rest of the day Variable Change of nurses shifts (n = 7826) All other hours of the day (n = 25,035) P value Maternal age, y 30.3 ± 5.1 30.2 ± 5.2 0.09 Gestational age at birth (weeks) 39.7 ± 1.09 39.8 ± 1.10 0.55 Nulliparity 2077 (35%) 7067 (37%) 0.01 Induction\augmentation of labor 2905 (37) 9368 (38) 0.62 Epidural analgesia 4746 (61) 15,396 (62) 0.16 Neonatal birth weight, g 3340 ± 422 3330 ± 423 0.06 Data is presented as mean ± S.D or N (%) Table 2 Maternal and neonatal adverse outcomes of women giving birth during the time of nurses shift change versus during the rest of the day Variable (%) Change of nurses shifts (n = 7826) All other hours of the day (n = 25,035) P value Vacuum assisted delivery 615 (7.9) 2002 (8.0) 0.69 Cesarean delivery 788 (10) 2443 (9.8) 0.45 Postpartum hemorrhage 294 (3.8) 1089 (4.4) 0.045 Third- and fourth-degree perineal laceration 106 (1.4) 372 (1.5%) 0.51 5-min Apgar score < 7 39 (0.5) 139 (0.6) 0.65 Umbilical pH < 7.2 170 (23) 580 (23) 0.96 Prolonged second stage 190 (2.5) 559 (2.2) 0.22 Maternal and fetal composite adverse outcome* 1309 (16.7%) 4219 (16.9%) 1.00 Data is presented as N (%) *Maternal and fetal composite adverse outcome was defined as the presence of any of the following: vacuum delivery, CD, prolonged second stage, postpartum hemorrhage, third and fourth degree perineal laceration, 5-min Apgar score < 7 and umbilical cord pH < 7.2 Table 3 General and obstetric characteristics of women giving birth during the time of the on-call physicians shift change versus during the rest of the day Variable Change of physicians shifts (n = 5155) All other hours of the day (n = 27,706) P value Maternal age, years 30.3 ± 5.1 30.2 ± 5.2 0.38 Gestational age at birth (weeks) 39.8 ± 1.09 39.8 ± 1.10 0.95 Nulliparity (%) 1303 (33.4) 7841 (37) < 0.0001 Induction\augmentation of labor (%) 1769 (34.3) 10,504 (38) < 0.0001 Epidural analgesia (%) 3067 (59.6) 17,075 (61.8) 0.003 Neonatal birth weight (gr) 3345 ± 416 3330 ± 424 0.019 Data is presented as mean ± S.D or N (%) Table 4 Maternal and neonatal adverse outcomes of women giving birth during the time of physicians on-call shift change versus during the rest of the day Variable (%) Change of physicians shifts (n = 5155) All other hours of the day (n = 27,706) P value Vacuum assisted delivery 397 (7.7) 2220 (8.0) 0.45 Cesarean delivery 517 (10.0) 2714 (9.8) 0.63 Postpartum hemorrhage 209 (4.1) 1174 (4.3) 0.54 Third- and fourth-degree perineal laceration 67 (1.3) 411 (1.5) 0.31 5-min Apgar score < 7 22 (0.5) 156 (0.6) 0.30 Umbilical pH < 7.2 94 (20.3) 656 (23.3) 0.15 Prolonged second stage 127 (2.5%) 622 (2.3%) 0.36 Maternal and fetal composite adverse outcome* 852 (16.5%) 4676 (16.9%) 1.00 Data is presented as N (%) *Maternal and fetal composite adverse outcome was defined as the presence of any of the following: vacuum delivery, CD, prolonged second stage, postpartum hemorrhage, third and fourth degree perineal laceration, 5-min Apgar score < 7 and umbilical cord pH < 7.2 CONCLUSION: Nurses' shift change and on-call physicians' shift change does not appear to be associated with an increase in adverse maternal or neonatal outcomes.

A Novel Partogram for Stages 1 and 2 of Labor Based on Fetal Head Station Measured by Ultrasound: A Prospective Multicenter Cohort Study.

OBJECTIVE: This study was aimed to describe continuous labor curves, including second stage, based on fetal head station. STUDY DESIGN: We performed a prospective multicenter cohort study. The inclusion criteria were women with singleton uncomplicated cephalic term pregnancies in labor, who delivered vaginally. We used a device that combines ultrasound imaging with position-tracking technology to monitor the head station noninvasively throughout labor. We collected data on demographics, labor parameters, and delivery and neonatal outcomes. RESULTS: A total of 613 women delivered vaginally, 327 (53.3%) were nulliparous, while 286 (46.7%) were multiparous. Time to delivery (TTD) diminished progressively with descent of the fetal head. When the head is engaged, the labor curve of multiparous women demonstrated a more prominent downward shift in curve as compared with nulliparous women. When comparing multipara and nullipara at engagement level, the median TTD was 1 and 1.62 hours, respectively. In 95% of women with unengaged head during the second stage, TTD of nulliparous and multiparous women were less than 3.8 and 3 hours, respectively. CONCLUSION: While current labor curves end at full dilatation, the described curves were developed throughout stages 1 and 2 of labor. The TTD, according to the station curves, shows an acceleration of labor, once passed the engagement level, especially in multiparous women.

Is it time to abandon episiotomy use? A randomized controlled trial (EPITRIAL).

INTRODUCTION AND HYPOTHESIS: The objective of this trial was to evaluate whether avoidance of episiotomy can decrease the risk of advanced perineal tears. METHODS: In this randomized (1:1) parallel-group superiority trial, primiparous women underwent randomization into "avoidance of episiotomy" (the study group in which episiotomy was allowed only in cases of fetal distress) or "standard care." The primary outcome was the incidence of advanced (3rd- and 4th-degree) perineal tears. RESULTS: The participants were randomized into "standard care" (n = 337) vs. "no episiotomy" (n = 339) groups, not differing in any demographic or obstetric characteristics. Episiotomy rates were significantly lower in the study group (19.6%) compared with the standard care group (29.8%, p = 0.004). Five (1.5%) advanced tears were diagnosed in the study group vs. ten = 3.0% in the controls, yielding an odds ratio of 0.50 (95% CI 0.17-1.50) in favor of the "no episiotomy" group (p = 0.296). No differences were noted in any secondary outcomes. By per protocol analysis (omitting cases in which episiotomy was performed for indications other than fetal distress in the study group), a trend to decreased risk of advanced tears in the study group was noted (p = 0.0956). By per protocol analyses, no severe tears were noted in the 53 vacuum deliveries in the study group vs. 4/65 (6.2%) tears in the controls (p = 0.126). CONCLUSIONS: Since decreased use of episiotomy was not associated with higher rates of severe tears or any other adverse outcomes, we believe this procedure can be avoided in spontaneous as well as vacuum-assisted deliveries. Trial registration no. NCT02356237.

Double-Balloon Device for 6 Compared With 12 Hours for Cervical Ripening: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether removal of a double-balloon device for cervical ripening for 6 compared with 12 hours in women with an unfavorable cervix will result in a shorter time to delivery, similar cervical ripening, and without affecting cesarean delivery rate. METHODS: In a prospective randomized trial, cervical ripening was performed using a double-balloon device. Women were randomized to removal of the device after 6 compared with 12 hours. Primary outcome was time to delivery. Secondary outcomes included mode of delivery, Bishop score, and maternal and neonatal adverse outcomes. A sample size of 100 nulliparous and 100 parous women was required assuming a 95% CI, power of 80%, and mean decrease of 6 hours to delivery between the groups. RESULTS: From March 2017 through February 2019, 688 women were screened, 243 were found eligible, and 197 were randomized as follows: nulliparous cohort (n=101): removal after 6 hours (n=48) compared with removal after 12 hours (n=53); parous cohort (n=96): removal after 6 hours (n=49) compared with removal after 12 hours (n=47). Insertion-to-delivery interval was significantly shorter in the 6-hour group for both nulliparous (25.6±12.8 hours vs 31.4±15.2 hours, P<.04; mean difference 5.8, 95% CI 0.2-11.3), and parous cohorts (18.0±6.8 hours vs 22.6±8.2 hours, P=.003; mean difference 4.7, 95% CI 1.6-7.7). Bishop score change and cesarean delivery rate were similar between groups regardless of parity. The 12-hour group in the combined cohort was associated with higher rates of maternal intrapartum fever (2% vs 10%, P=.02; odds ratio 5.3, 95% CI 1.1-24.8). CONCLUSION: Insertion-to-delivery interval is shorter after 6 compared with 12 hours for both nulliparous and parous women. Cervical ripening with a double-balloon device may be achieved in 6 hours. The longer time was associated with a higher rate of intrapartum fever. Six hours should be considered as standard placement time for double-balloon catheters. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03045939.

Induction of labor versus expectant management among women with macrosomic neonates: a retrospective study.

Background: The macrosomic fetus predisposes a variety of adverse maternal and perinatal outcomes. Although older studies have shown no benefit in inducing women of suspected macrosomic fetuses, more updated studies show different information.Objectives: The aim of our study was to compare induction of labor versus expectant management among women with macrosomic neonates weighing more than 4000 g at term (between 37°/7 and 416/7 weeks' gestation).Study design: This was a retrospective cohort study of all live-born singleton pregnancies with macrosomic newborns who were delivered at our institution between 1 January 2000 and 1 June 2015. We compared the outcomes of induction of labor, at each gestational age (GA), between 37 and 41 weeks (study group) with ongoing pregnancy. The primary outcome was cesarean section (CS) rate. Secondary outcomes were composite maternal and neonatal outcome and birth injuries.Results: Overall, out of 3095 patients with macrosomic newborns who were included in the study, 795 women (25.7%) underwent induction of labor. The cesarean section rate was not found to be significantly different between the groups at all gestational ages, nor was the vaginal delivery rate. After adjusting for confounders, induction of labor at 40 and 41 weeks' gestation was associated with composite maternal outcome (adjusted odds ratio (aOR) 1.6, 95% confidence interval (CI): 1.3-2.1; aOR 1.7, 95% CI: 1.3-2.2, respectively) and composite neonatal outcome (aOR 1.6, 95% CI: 1.1-2.4; aOR 1.8, 95% CI: 1.1-2.9). Induction of labor at 40 weeks' gestation was also associated with increased risk of birth injuries (aOR 2.9, 95% CI: 1.4-6).Conclusions: Compared with ongoing pregnancy, induction of labor of women with macrosomic neonates between 37 and 41 weeks of gestation does not reduce the CS rate, nor does it increase the vaginal delivery rate. Moreover, induction of labor of those women beyond 39 weeks' gestation is associated with composite adverse maternal/neonatal outcome, specifically birth injuries.

Who may accompany the parturient to the delivery room?

OBJECTIVE: To assess the association of the attendant of the parturient (husband or mother or both), on labor duration, mode of delivery, maternal and neonatal complications. STUDY DESIGN: A retrospective cohort study, over a 4-year period, of women admitted to the delivery room accompanied by their husband, their mother or both. Medical records were reviewed for demographic, medical and obstetrical history. RESULTS: Overall, 3029 patients were included, 2192 were accompanied by their husband; 127 were accompanied by their mother and 710 were accompanied by both. Women accompanied by their husbands were significantly older and more likely to be multiparous than women accompanied by their mother (30.2 years vs. 27.8 years, P < 0.001 and 60% vs. 48.8%, P = 0.02, respectively). Compared to women supported during labor by their mothers, women supported only by their husbands spent less hours in the delivery room (from admission to delivery) (11.1 h vs. 13.7 h, P = 0.02). While the nature of the attendant had no influence on the mode of delivery among nulliparous women (p = 0.13), multiparous women supported by the mothers had a significantly higher rate of cesarean delivery compared to those supported only by their husband or by both (OR = 2.07, 95% CI = [1.317-3.246], P = 0.002, OR = 3.33, 95% CI = [1.623-6.849], P = 0.001, respectively). CONCLUSIONS: Women supported by their mothers during labor have a longer second stage of labor, a decreased rate of vaginal delivery and an increased risk for cesarean delivery compared to women supported by their husbands. Future large prospective studies are needed to confirm our observation and to find causative affect.

Differences in outcomes between cesarean section in the second versus the first stages of labor.

OBJECTIVE: We aimed to compare maternal morbidity and mortality of cesarean sections (CS) in the second versus first stage of labor. STUDY DESIGN: Retrospective study of all CS at a single, university-affiliated medical center, between January 2010 and December 2014. Eligibility was limited to term, singleton pregnancies with cephalic presentation. Maternal outcomes of second-stage CS were compared to those of first-stage CS. The primary outcome was defined as estimated blood loss >1000 ml. RESULTS: Overall, 1004 women met the inclusion criteria, of which 290 (29%) had a second-stage CS and 714 (71%) had a first-stage CS. Women in the second-stage CS group had a higher nulliparity and hypertensive disorders rates and a lower rate of previous CS. Second-stage CS was associated with more than double the rate of estimated blood loss >1000 ml (9.7% versus 3.8%, p<.001), and more prone to unintentional uterine incision extension, uterine atony, hemoglobin decrease >2 g/l and antibiotic treatment for suspected endometritis. In a multivariable logistic regression model, second-stage CS was found to be independently associated with unintentional uterine incision extension (OR 6.8, 95% CI 4.1-11.2), uterine atony (OR 3.3, 95% CI 1.4-8.0) and antibiotic treatment for suspected endometritis (OR 2.6, 95% CI 1.4-5.1), but not with excessive blood loss (OR 1.5, 95% CI 0.8-2.8). Additionally, failed assisted vaginal delivery prior to second-stage CS was not associated with a higher rate of complications. CONCLUSION: Second-stage CS is associated with higher rates of adverse maternal outcomes, mainly unintentional uterine incision extension, uterine atony, and suspected endometritis.

Does prenatal identification of fetal macrosomia change management and outcome?

PURPOSE: To assess whether there is an association between predicted fetal macrosomia and adverse outcomes in macrosomic newborns (> 4000 g), based on a sonographic evaluation up to 2 weeks prior to delivery. METHODS: A retrospective cohort study of 3098 mothers of macrosomic babies who were delivered at our institution (2000-2015). We compared the management and outcomes of women with predicted fetal macrosomia with that of women with unknown fetal macrosomia. The primary outcomes were cesarean section (CS) rate and postpartum hemorrhage. Secondary outcomes were composite maternal and neonatal outcomes and birth injuries. RESULTS: In 601 (19.4%) women fetal macrosomia was predicted, and in 2497 (80.6%) women, fetal macrosomia was unknown. CS rate was more than 3.5 times higher in the group of predicted macrosomia (47.2% vs. 12.7%, P < 0.001) than those with unpredicted macrosomia; not only due to non-progressive labor, but for non-reassuring heart rate as well. However, predicted fetal macrosomia reduced the risk of postpartum hemorrhage (aOR 0.5, 95% CI 0.2-1.0), maternal (aOR 0.3, 95% CI 0.2-0.5) and neonatal composite adverse outcomes (aOR 0.7 95% CI 0.6-0.9). It was also associated with increased risk for induction of labor, episiotomy, 3rd- or 4th-degree tears and a longer maternal hospitalization. Birth injuries and shoulder dystocia were not different between the groups. CONCLUSIONS: Antepartum CS was found to be associated with predicted fetal macrosomia. Moreover, a planned CS due to macrosomia was associated with reduced risk for postpartum hemorrhage, maternal and neonatal outcome, even for babies with a mean birth weight < 4500 g.

No episiotomy versus selective lateral/mediolateral episiotomy (EPITRIAL): an interim analysis.

INTRODUCTION AND HYPOTHESIS: The objective of this trial was to evaluate whether avoiding episiotomy can decrease the risk of advanced perineal tears. MATERIAL AND METHODS: In this randomized (1:1) parallel-group superiority trial, primiparous women underwent randomization into standard care (155 cases) vs. no episiotomy (154 cases) groups. The primary endpoint was the incidence of advanced (3rd- and 4th-degree) perineal tears. Secondary outcomes included perineal integrity, suturing characteristics, second-stage duration, incidence of postpartum hemorrhage, neonatal variables, and various postpartum symptoms 2 days and 2 months after delivery. RESULTS: At prespecified 1-year interim analysis, the groups did not differ in terms of baseline demographic and obstetric characteristics. Six advanced perineal tears (3.9%) were diagnosed in the standard care group vs. two in no episiotomy group (1.3%), yielding a calculated odds ratio (OR) of 0.33 [95% confidence interval (CI) 0.06-1.65). Unexpectedly, rates of episiotomy performance also did not significantly vary between groups: 26.5% (41 cases) vs. 21.4% (33 cases), respectively, p = 0.35. No significant differences were noted in any secondary outcomes. CONCLUSIONS: No difference in the rates of advanced perineal tears was found between groups; however, the main limitation of our study was unexpectedly high rates of episiotomy in the nonepisiotomy group. Thus, the main conclusion is that investigator monitoring and education should be continuously practiced throughout the trial duration, stressing the importance of adherence to the protocol.

When should repeat cesarean delivery be scheduled, after two or more previous cesarean deliveries?

BACKGROUND: The optimal gestational age for a planned high-order cesarean delivery (CD) reflects the balance between the risk of neonatal morbidity and the risk of unscheduled cesarean delivery prior to the scheduled date. METHODS: A retrospective cohort study of 656 women with ≥2 previous CDs were divided in two groups of women based on the gestational age at which the CD was scheduled: "38 group" and "39 group". Medical records were reviewed for demographic, medical and obstetrical history, and for adverse maternal and neonatal outcomes. RESULTS: The rate of unscheduled CDs was significantly higher among the 39 group (23.2% vs. 12.7%). There were no significant differences in the rate of maternal or neonatal composite adverse outcome between the two groups. The rate of neonatal respiratory morbidity, however, was higher among the 38 group (5.8% vs. 2.1%).Compared with planned CD, unscheduled CD was associated with a similar rate of maternal composite adverse outcome, but with increased rate of neonatal composite adverse outcome (23.3% vs. 8%, respectively). In a multivariable logistic regression analysis we found that this latter association was due to the earlier actual gestational age at delivery in cases of unscheduled versus planned CD. CONCLUSIONS: Planned CD at 39 weeks, rather than at 38 weeks, is associated with more unscheduled CDs, a similar rate of maternal and neonatal composite morbidity, but a decreased rate of neonatal respiratory morbidity.

When should pregnancies that extended beyond term be induced?

OBJECTIVE: To compare maternal and neonatal outcomes associated with a policy for induction of labor at ≥ 41 versus at ≥42 weeks'. STUDY DESIGN: Retrospective cohort study of a 2 years' period before and after policy change from induction of labor at ≥ 42 gestational weeks' versus ≥41 gestational weeks. RESULTS: During the 41-policy period (N = 968), the induction rate was higher, 60% versus 40% (p < 0.0001) while the cesarean delivery (CD) rate was lower, 15% versus 19.4% (p = 0.0135). Moreover, among women that were induced, the rate of CD was lower during the 41-policy period, 19% versus 27% (p = 0.0067). No significant differences in maternal or neonatal outcomes were noted. There was one case of intrauterine fetal death at 41 + 4 weeks during the 42-policy period. CONCLUSION: As a policy for induction of labor at ≥ 41 reduces the rate of CD without any adverse maternal or neonatal outcomes, such a policy seems to be superior to a policy for induction at ≥ 42 weeks.

Does cesarean section before the scheduled date increase the risk of neonatal morbidity?

BACKGROUND: Previous studies led to the recommendation to schedule planned elective cesarean deliveries at or after 39 weeks of gestation and not before 38 weeks. The question is whether this practice is appropriate in face of possible risks to the newborn should the pregnancy have to be ended by cesarean section before the scheduled date. OBJECTIVES: To compare the outcomes of newborn infants who were delivered on their scheduled day by elective cesarean section versus those who required delivery earlier. METHODS: This single-center retrospective study was based on medical records covering a period of 18 months. We compared the neonatal outcomes of 272 infants delivered by elective cesarean section as scheduled (at 38.8 +/- 0.8 weeks gestation)and 44 infants who had to be delivered earlier than planned j(at 37.9 +/- 1.1 weeks). RESULTS: We found no morbidity directly related to delivery by cesarean section before the scheduled date. There were no significant differences in the need for resuscitation after delivery. Although more of the infants who were delivered early were admitted to intensive care and overall stayed longer in the hospital (5.8 +/- 7.3 vs. 3.9 +/- 0.8 days, P < 0.02), their more severe respiratory illness and subsequent longer hospitalization was the result of their younger gestational age. Transient tachypnea of the newborn was associated with younger gestational age at delivery in both groups. CONCLUSIONS: We suggest continuing with the current recommendation to postpone elective cesarean singleton deliveries beyond 38-39 weeks of gestation whenever possible.

The effect of timing of maternal tetanus, diphtheria, and acellular pertussis (Tdap) immunization during pregnancy on newborn pertussis antibody levels - a prospective study.

BACKGROUND: The Centers for Disease Control and Prevention recommend Tdap immunization during pregnancy, preferably at 27-36 weeks. AIM: To ascertain whether there is a preferential period of maternal Tdap immunization during pregnancy that provides the highest concentration of pertussis-specific antibodies to the newborn. METHODS: This prospective study measured pertussis-specific antibodies in paired maternal-cord sera of women immunized with Tdap after the 20th week of their pregnancy (n=61). RESULTS: The geometric mean concentrations (GMCs) of Immunoglobulin G (IgG) to pertussis toxin (PT) were higher in the newborns' cord sera when women were immunized at 27-30(+6) weeks (n=21) compared with 31-36 weeks (n=30) and >36 weeks (n=7), 46.04 international units/milliliter (IU/mL) (95% CI, 24.29-87.30) vs. 8.69IU/mL (95% CI, 3.66-20.63) and 21.12IU/mL (95% CI, 7.93-56.22), p<0.02, respectively. The umbilical cord GMCs of IgG to filamentous hemagglutinin (FHA) were higher in the newborns' cord sera when women were immunized at 27-30(+6) weeks compared with 31-36 weeks and >36 weeks, 225.86IU/mL (95% CI, 182.34-279.76) vs. 178.31IU/mL (95% CI, 134.59-237.03) and 138.03IU/mL (95% CI, 97.61-195.16), p<0.02, respectively. CONCLUSIONS: Immunization of pregnant women with Tdap between 27-30(+6) weeks was associated with the highest umbilical cord GMCs of IgG to PT and FHA compared with immunization beyond 31 weeks gestation. Further research should be conducted to reaffirm these finding in order to promote an optimal pertussis controlling policy.

The induction of breast milk pertussis specific antibodies following gestational tetanus-diphtheria-acellular pertussis vaccination.

BACKGROUND: Center for Disease Control and Prevention recommends vaccination of pregnant women with tetanus-diphtheria-acellular pertussis (Tdap). AIM: To measure pertussis specific antibodies, total protein and their ratio in breast milk following gestational Tdap vaccination. METHODS: Women who received Tdap after the 20th week of pregnancy were recruited and unvaccinated women served as controls. Breast milk total protein, immunoglobulin A (IgA) to pertussis toxin (PT), filamentous hemagglutinin (FHA) and immunoglobulin G (IgG) to PT, FHA and pertactin (PRN) were measured. To overcome the dilution that occurs in the transition from colostrum to mature breast milk, we calculated pertussis specific antibody to total protein ratio. RESULTS: Pertussis specific IgA was the predominant pertussis immunoglobulin in the colostrum of Tdap vaccinated women with the geometric mean concentrations (GMCs) of IgA to FHA higher than for IgA to PT, 24.12 ELISA units/milliliter (EU/mL) vs. 8.18EU/mL, respectively, p<0.004. There were differences between the vaccinated women and controls in the GMCs of IgA to FHA and IgG to PRN in the colostrum, 24.12EU/mL vs. 6.52EU/mL, p=0.01 and 2.46EU/mL vs. <0.6EU/mL, p=0.03, respectively. The GMCs of total protein showed significant decline over 8 weeks in the vaccinated women and controls, p<0.004. Among vaccinated women, there was significant decline in the GMCs of IgA to PT and FHA over 8 weeks, p<0.001. The geometric mean ratio of IgA to FHA to total protein also declined significantly over 8 weeks in the vaccinated women, p<0.01, demonstrating a true decrease, however, pertussis IgA was measurable at 8 weeks. CONCLUSIONS: Select colostrum pertussis antibody levels were significantly higher among women vaccinated with Tdap during pregnancy compared with unvaccinated women. Among vaccinated women, maximal levels of pertussis specific IgA were in the colostrum but still detected at 8 weeks. Lactation may augment infant's protection against pertussis.

The role of the carbohydrate recognition domain of placental protein 13 (PP13) in pregnancy evaluated with recombinant PP13 and the DelT221 PP13 variant.

INTRODUCTION: Placental protein 13 (PP13), a placenta specific protein, is reduced in the first trimester of pregnancy in women who subsequently develop preeclampsia. A naturally occurring PP13 deletion of thymidine at position 221 (DelT221 or truncated variant) is associated with increased frequency of severe preeclampsia. In this study we compared the full length (wildtype) PP13 and the truncated variant. METHODS: Full length PP13 or its DelT221 variant were cloned, expressed and purified from E-Coli. Both variants were administrated into pregnant rats at day 8 of pregnancy for slow release (>5 days) through osmotic pumps and rat blood pressure was measured. Animals were sacrificed at day 15 or day 21 and their utero-placental vasculature was examined. RESULTS: The DelT221 variant (11 kDA) lacked exon 4 and a part of exon 3, and is short of 2 amino acids involved in the carbohydrate (CRD) binding of the wildtype (18 kDA). Unlike the wildtype PP13, purification of DelT221 variant required special refolding. PP13 specific poly- clonal antibodies recognized both PP13 and DelT221 but PP13 specific monoclonal antibodies recognized only the wildtype, indicating the loss of major epitopes. Wildtype PP13 mRNA and its respective proteins were both lower in PE patients compared to normal pregnancies. The DelT221 mutant was not found in a large Caucasian cohort. Pregnant rats exposed to wildtype or DelT221 PP13 variants had significantly lower blood pressure compared to control. The wildtype but not the DelT221 mutant caused extensive vein expansion. CONCLUSION: This study revealed the importance of PP13 in regulating blood pressure and expanding the utero-placental vasculature in pregnant rats. PP13 mutant lacking amino acids of the PP13 CRD domain fails to cause vein expansion but did reduce blood pressure. The study provides a basis for replenishing patients at risk for preeclampsia by the full length but not the truncated PP13.

Prediction of preeclampsia by placental protein 13 and background risk factors and its prevention by aspirin.

AIM: Evaluation of placental protein 13 (PP13) and risk factors (RFs) as markers for predicting preeclampsia (PE) and use of aspirin for PE prevention. MATERIALS AND METHODS: First-trimester pregnancy screening was based on having PP13 level ≤0.4 multiple of the median (MoM) and/or at least one major risk factor (RF) for PE. Management was by routine care or combined with daily treatment with 75 mg aspirin between 14 and 35 weeks of gestation. RESULTS: Of 820 deliveries, 63 women developed PE (7.7%). Median PP13 levels was 0.2MoM in the PE group compared with 0.83MoM among unaffected and 1.0MoM in unaffected not treated with aspirin (P<0.0001). Low PP13 was a better predictor for PE versus major RFs, particularly for young nuliparous. Combining low PP13 with RFs increased prediction accuracy. Mean arterial pressure (not included in the initial prediction), could add to prediction accuracy when combined with low PP13 and RFs. PE prevention by aspirin was most effective when the risk was determined by low PP13 alone, less effective for combining low PP13 with RFs, and ineffective when determined by RFs alone. CONCLUSION: When PE risk is determined by low first trimester PP13 or by combined low PP13 and RFs, prevention with aspirin is warranted.

Adrenalectomy for adrenocortical adenoma causing Cushing's syndrome in pregnancy: a case report and review of literature.

We present a case of adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome diagnosed in a patient in the third trimester of her pregnancy, with an adrenal mass observed on imaging studies. Laparoscopic adrenalectomy was performed successfully at 32 weeks. To the best of our knowledge, this is the latest gestational age at which laparoscopic adrenalectomy has been reported. We present the various considerations for determining the surgical approach and the optimal timing for surgery. Adrenalectomy during pregnancy for the treatment of Cushing's syndrome caused by adrenocortical adenoma has been reported in 23 patients in the English-language medical literature to date and seems safe and beneficial. According to the data, surgical treatment has led to a reduction in perinatal mortality and maternal morbidity rates, but has not affected the occurrence of preterm birth and intrauterine growth restriction. The best outcome can be achieved by a multidisciplinary approach, with a team comprising a maternal-fetal medicine specialist, an endocrinologist and a surgeon. The timing of surgery and the surgical approach need to be determined according to the surgeon's expertise, the severity of the condition, the patient's preferences, and gestational age. Laparoscopy may prove to be the preferred surgical approach. The small number of cases precludes providing evidence-based recommendations.

Economic assessment of screening for pre-eclampsia.

BACKGROUND: Pre-eclampsia is a major contributor to maternal and neonatal morbidity and mortality. Our objectives in this study are to economically assess, from the payer perspective, routine screening for pre-eclampsia using placental markers -placental protein 13 and placental growth factor - and uterine artery Doppler compared with standard care. METHODS: A decision model was developed, which progresses through three sequential endpoints, and compares screening with no screening: (1) Pre-eclampsia yes/no: calculation of the incremental cost of pre-eclampsia-case averted; (2) Hospital discharge: calculation of the mean accumulated costs until discharge after delivery; and (3) Offspring death: calculation of the incremental cost per quality of life-adjusted life-year gained by screening. Data used includes: (1) Obstetrical data of 14 500 births; (2) cost data from the Israeli Ministry of Health and the literature; and (3) screening performance and outcome from the literature. RESULTS: (1) The incremental cost of pre-eclampsia-case averted is $66,949 and $24,723 when the prevalence is 1.7 and 5% respectively. (2) With test cost of $112, the total cost until discharge with/without screening is equal. With pre-eclampsia prevalence of 3%, screening is cheaper. (3) The cost per quality of life-adjusted life-year with screening is $18,919 and < $10,000 with pre-eclampsia prevalence of 1.7 and 3%, respectively. CONCLUSIONS: Screening for pre-eclampsia is cost-effective under various scenarios.