The Maternal Impact, Health Burden, and Postpartum Sequela in Triplet Pregnancies: A Retrospective Cohort.

OBJECTIVE: The aim of the study is to describe the maternal health burden and perinatal outcomes in triplet pregnancies, and identify the maternal and pregnancy indicators associated with increased perinatal morbidity and mortality. STUDY DESIGN: This is a retrospective cohort study of triplet pregnancies from 2007 to 2014. Maternal data were manually collected and assessed until 6 weeks postpartum, and neonatal data were assessed until hospital discharge or death. RESULTS: Eighty-two triplet pregnancies were identified with 246 babies born. Mean gestational age at delivery was 32.3 (standard deviation [SD] ± 3.6) weeks and average birth weight was 1,726 g (SD ± 500). There were 12 perinatal deaths and 25 (10.2%) infants diagnosed with a congenital anomaly. Prior preterm birth and nulliparity had a negative impact on gestational age at delivery (p = 0.016) as compared with prior full-term births. Pregnancy complications (preeclampsia or hypertensive disorders [46.3%], gestational diabetes [28%], postpartum hemorrhage [9.8%], and blood transfusions [8.5%]) also impacted gestational age at delivery (33.0 vs. 34.0 weeks, p = 0.031). Spontaneous conception, chorionicity, and maternal medical problems did not have an impact on median gestational age. CONCLUSION: Nulliparity and presence of pregnancy complications are pertinent to triplet outcomes. This study provides valuable information for anticipatory guidance and preconception counseling to patients considering artificial reproductive technology.

Delayed clamping vs milking of umbilical cord in preterm infants: a randomized controlled trial.

BACKGROUND: It has been established that delayed umbilical cord clamping in preterm infants results in improvement in neonatal anemia, need for transfusion, incidence of necrotizing enterocolitis, and intraventricular hemorrhage by increasing neonatal circulating blood volume. However, the effects of umbilical cord milking as an alternative to delayed clamping in preterm infants are unclear. OBJECTIVE: The primary objective of this study was to compare the effect of delayed clamping vs milking of the umbilical cord on the initial hematocrit concentration in preterm births (23-34 weeks gestation). In addition, we sought to compare the effects of delayed clamping vs milking on the incidences of intraventricular hemorrhage, necrotizing enterocolitis, and need for transfusion (secondary objectives). STUDY DESIGN: The study was an unblinded randomized controlled trial of singleton preterm infants who were born 23 weeks 0 days to 34 weeks 6 days gestation and were assigned to 1 of 2 controlled study groups: delayed cord clamping for 60 seconds or milking of the cord towards the infant 4 times before clamping. Randomization occurred via block randomization with an allocation ratio of 1 to 1. The patients' third stage of delivery was standardized for route of delivery and randomization arm. All comparisons were preformed with an intent-to-treat analysis approach. The study was powered at 80% with a probability value of .05 for the primary outcome measure of a hematocrit difference of 3% between the 2 groups. RESULTS: Of the 204 randomized patients, 104 were assigned to the delayed subgroup, and 100 were assigned to the milking subgroup. There were no significant differences in baseline maternal characteristics noted between groups. Though there was not any statistically significant difference in neonatal outcomes between the cord clamping and milking groups, the occurrences of transfusion (15.5% vs 9.1%; P=.24), necrotizing enterocolitis (5.8% vs 3.0%; P=.49), and intraventricular hemorrhage (15.5% vs 10.1%; P=.35) were all lower in the milking group. The milking group had higher initial hematocrit concentration compared with the delayed clamping group, although this was not significant (51.8 [6.2%] vs 49.9 [7.7%]; P=.07]. Peak bilirubin levels and need for phototherapy were similar between groups. CONCLUSION: This study demonstrates that milking the umbilical cord may be an acceptable alternative to delayed cord clamping because there were similar effects on neonatal hematocrit concentrations and the need for neonatal transfusions and no increased risk for complications or neonatal morbidity. The present data support the concept that milking of the umbilical cord may offer an efficient and timely method of providing increased blood volume to the infant.

Randomized controlled trial of intravenous acetaminophen for postcesarean delivery pain control.

BACKGROUND: Cesarean delivery is a common surgery in the United States, with 1.3 million performed during 2009.1 Obstetricians must balance the growing concern with opioid abuse, dependence, and side effects with optimal postoperative pain control. Intravenous acetaminophen may represent an additional method to decrease the reliance on opioid medications and improve postoperative pain following cesarean delivery. OBJECTIVE: The objective of the study was to determine whether the administration of intravenous acetaminophen following routine scheduled cesarean delivery would decrease the need for narcotic medications to control postoperative pain. STUDY DESIGN: This was an institutional review board-approved, double-blind, placebo-controlled, randomized trial, registered on clinicaltrials.gov (number 02046382). Women scheduled to undergo cesarean delivery with regional anesthesia at term were recruited. All perioperative and postpartum care was standardized via study order sets. Study patients were given all medications in a standardized manner receiving either acetaminophen 1000 mg intravenously or 100 mL saline (placebo) every 8 hours for 48 hours for a total of 6 doses. The pharmacy prepared intravenous acetaminophen and saline in identical administration bags labeled study drug to ensure blinding. The initial dose of study drug was given within 60 minutes of skin incision. Quantity of breakthrough and scheduled analgesic medications and self-reported pain levels on the Faces Pain Scale (0-10) before and after study drug administration were collected. Patient demographics were extracted from the chart. Power calculation determined that 45 patients per arm were required to detect a 30% reduction in postcesarean narcotic requirement with 80% power and a significance level of P = .05. RESULTS: A total of 133 patients were consented for the study. Twenty-nine were excluded and 104 patients completed the study: 57 received intravenous acetaminophen and 47 received placebo. There were no differences in baseline demographic characteristics including patient age, body mass index, gravidity, parity, race, comorbidities, or number of prior cesarean deliveries. There were no differences between groups in estimated blood loss or length of stay. The total amount of oral narcotic medications consumed by patients receiving intravenous acetaminophen was significantly reduced when compared with the placebo group (47 mg vs 65 mg of oxycodone; P = .034). The total amount of ibuprofen used between groups was not different. There was no difference in pain scores between groups before and after study dose administration. There was no significant difference in narcotic side effects (nausea/emesis, respiratory depression, constipation) in either study arm. CONCLUSION: Intravenous acetaminophen in the postoperative period following cesarean delivery resulted in a significant decrease in oral narcotic consumption for pain control.

Placental Infection With Ureaplasma species Is Associated With Histologic Chorioamnionitis and Adverse Outcomes in Moderately Preterm and Late-Preterm Infants.

OBJECTIVE: The human Ureaplasma species are the microbes most frequently isolated from placentae of women who deliver preterm. The role of Ureaplasma species has been investigated in pregnancies at <32 weeks of gestation, but currently no studies have determined the prevalence of ureaplasmas in moderately preterm and late-preterm (hereafter, "moderate/late preterm") infants, the largest cohort of preterm infants. METHODS: Women delivering moderate/late preterm infants (n = 477) and their infants/placentae (n = 535) were recruited, and swab specimens of chorioamnion tissue, chorioamnion tissue specimens, and cord blood specimens were obtained at delivery. Swab and tissue specimens were cultured and analyzed by 16S ribosomal RNA polymerase chain reaction (PCR) for the presence of microorganisms, while cord blood specimens were analyzed for the presence of cytokines, chemokines, and growth factors. RESULTS: We detected microorganisms in 10.6% of 535 placentae (443 were delivered late preterm and 92 were delivered at term). Significantly, Ureaplasma species were the most prevalent microorganisms, and their presence alone was associated with histologically confirmed chorioamnionitis in moderate/late preterm and term placentae (P < .001). The presence of ureaplasmas in the chorioamnion was also associated with elevated levels of granulocyte colony-stimulating factor (P = .02). CONCLUSIONS: These findings have important implications for infection and adverse pregnancy outcomes throughout gestation and should be of major consideration for obstetricians and neonatologists.

The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis.

BACKGROUND: Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is not uncommonly associated with chorioamnionitis. We recently have demonstrated that the placenta harbors a unique microbiome with similar flora to the oral community. We also have shown an association of these placental microbiota with PTB, history of antenatal infection, and excess maternal weight gain. On the basis of these previous observations, we hypothesized that the placental membranes would retain a microbiome community that would vary in association with preterm birth and chorioamnionitis. OBJECTIVE: In the current study, we aimed to examine the differences in the placental membrane microbiome in association with PTB in both the presence and absence of chorioamnionitis and/or funisitis using state-of-the-science whole-genome shotgun metagenomics. STUDY DESIGN: This was a cross-sectional analysis with 6 nested spontaneous birth cohorts (n = 9-15 subjects/cohort): Term gestations without chorioamnionitis, term with chorioamnionitis, preterm without chorioamnionitis, preterm with mild chorioamnionitis, preterm with severe chorioamnionitis, and preterm with chorioamnionitis and funisitis. Histologic analysis was performed with Redline's criteria, and inflammatory cytokines were analyzed in the cord blood. DNA from placental membranes was extracted from sterile swabs collected at delivery, and whole-genome shotgun sequencing was performed on the Illumina HiSeq platform. Filtered microbial DNA sequences were annotated and analyzed with MG-RAST (ie, Metagenomic Rapid Annotations using Subsystems Technology) and R. RESULTS: Subjects were assigned to cohorts on the basis of gestational age at delivery and independent scoring of histologic chorioamnionitis. We found that preterm subjects with severe chorioamnionitis and funisitis had increases in cord blood inflammatory cytokines. Of interest, although the placental membrane microbiome was altered in association with severity of histologic chorioamnionitis (permutational multivariate analysis of variance P = .005), there was no observable impact with either betamethasone or antibiotic treatment. In preterm subjects with chorioamnionitis, we found a high abundance of both urogenital and oral commensal bacteria. These alterations in the microbiome were accompanied by significant variation (P < .05) in microbial metabolic pathways important in the glucose-fed pentose phosphate pathway (term subjects), or glycerophopholipid metabolism, and the biosynthesis of the siderophore group nonribosomal peptides (preterm subjects). CONCLUSION: Consistent with ours and others previous findings, women who experienced spontaneous PTB harbor placental microbiota that further differed by severity of chorioamnionitis. Integrative metagenomic analysis revealed significant variation in distinct bacterial metabolic pathways, which we speculate may contribute to risk of preterm birth with and without severe chorioamnionitis.

The GoMo study: a randomized clinical trial assessing neonatal pain with Gomco vs Mogen clamp circumcision.

OBJECTIVE: Our objective was to compare the pain/stress levels of newborns among the 2 most common circumcision techniques after resident-wide education. STUDY DESIGN: The study period of this randomized control trial was October 2012 through March 2014. Following informed consent, full-term males from uncomplicated singleton pregnancies were randomized to Gomco (n=137) or Mogen (n=137) devices. Resident-wide education for an obstetrics and gynecology residency program at a single institution was performed to ensure standardized training. All infants received a subcutaneous ring block before the procedure and oral sucrose intraoperatively. The primary outcome was neonatal pain assessed physiologically by salivary cortisol levels (enzyme-linked immunosorbent assay) and clinically by a validated neonatal pain score (crying, requires increased oxygen administration, increased vital signs, expression, sleeplessness [CRIES]). Secondary outcomes were immediate complications, duration of procedure, and short-term outcomes as reported by mothers and pediatricians. A sample size of 274 (accounting for 20% loss of follow-up) was determined sufficient to detect a mean difference of 1.22 µg/dL in cortisol levels (Gomco, SD±3.34; Mogen, SD±0.81) with 80% power, P=.05 level of significance. RESULTS: A total of 251 infants completed the protocol. There were no significant differences in maternal or neonatal demographics including preoperative heart rate and mean arterial pressure. In the Mogen circumcision, the percentage change of cortisol was significantly lower than Gomco (279.1±498.15 vs 167.75±272.22; P=.049). There were no differences in postoperative CRIES scores. Postoperative heart rate was higher in infants undergoing Gomco circumcision than Mogen circumcision (138.7±16.5 vs 133.4±17.5; P=.015) as was mean arterial blood pressure (63.3±9.2 vs 60.4±8.6; P=.012). Mogen circumcisions were shorter (7.00±2.97 vs 3.65±1.84 minutes; P<.001). There were no significant differences in bleeding complications. A total of 168 maternal surveys were completed, with 98.7% maternal satisfaction in Gomco vs 98.9% in Mogen. There were no reports of bleeding after discharge or circumcision revisions in either group to date. CONCLUSION: Mogen clamp is associated with less neonatal pain physiologically by significantly lower percentage change in salivary cortisol, lower heart rate, and mean arterial blood pressure. There was no difference in CRIES scores. Mogen clamp circumcision duration is significantly shorter than Gomco clamp. Both methods demonstrate satisfactory maternal and pediatrician short-term follow-up.

A randomized trial comparing metallic and absorbable staples for closure of a Pfannenstiel incision for cesarean delivery.

OBJECTIVE: The purpose of the study is to compare postoperative pain, cost, speed of closure, and patient satisfaction of Pfannenstiel skin incisions closed with traditional metallic staples vs absorbable staples after cesarean delivery. It is hypothesized that incisions closed with absorbable staples will cause less postoperative pain than traditional metallic staples. STUDY DESIGN: A randomized, controlled trial was conducted from July 2010 through May 2011. Patients undergoing a scheduled cesarean delivery via a Pfannenstiel skin incision were recruited. Patients were randomized into the control group (metallic staples) or the experimental group (absorbable staples). The postpartum nurse and patient were blinded to the type of staples. Postoperative pain was assessed using a visual analog scale on both postoperative day 1 and day of discharge, and the total dose of oral narcotics taken during the postoperative period was assessed. RESULTS: In all, 100 patients enrolled in the study: 50 in each group. Based on visual analog scale scores, there were no significant differences between the 2 groups on postoperative day 1 or day of discharge. There were no significant differences in the total dose of oral narcotics taken or in wound complication rates. The time for skin closure was significantly different: 3.5 ± 1.7 for absorbable and 1.39 ± 0.7 minutes for metallic staples (P < .0001). The calculated cost of each device, including placement and removal, was $285.60 for the absorbable and $150.79 for the metallic staples. CONCLUSION: Postoperative pain is comparable for both devices. The absorbable staple skin closure time, and therefore cost, is significantly greater than for metallic staples.

The effect of combined spinal epidural versus epidural analgesia on fetal heart rate in laboring patients at risk for uteroplacental insufficiency.

BACKGROUND: The effects of neuraxial analgesia on fetal heart tracings have been studied in "healthy" pregnancies. Our objective was to compare the impact of intrapartum epidural analgesia (EA) versus combined spinal epidural analgesia (CSE) on fetal heart rate changes in pregnancies at risk for uteroplacental insufficiency (UPI). METHODS: Singleton pregnancies diagnosed with chronic hypertension, gestational hypertension and/or preeclampsia, and/or fetal growth restriction (FGR) and receiving neuraxial analgesia intrapartum from 2012 to 2015 were studied retrospectively. The primary outcome was change in fetal heart rate (FHR) category following neuraxial analgesia. Manual review of all FHR tracings was performed and classified by the National Institute of Child Health and Human Development (NICHD) categories. Data collection included maternal demographics, blood pressure, uterine tachysystole, uterine hypertonus, mode of delivery, interventions for FHR abnormalities and neonatal outcomes. RESULTS: Of laboring patients at risk for UPI, 110 patients received EA and 127 patients received CSE. The rate and change in FHR categories and abnormalities following neuraxial analgesia were the same in both groups. Both EA and CSE resulted in a significant increase in NICHD FHR category II, from 27.3 to 65.5% for EA and 20.9 to 64.3% for CSE. The occurrence of maternal hypotension, uterine tachysystole, interventions for FHR abnormalities, and uterine hypertonus following neuraxial analgesia was not found to be significantly different between the two groups. When compared to the EA group, CSE had a higher rate of NICU admission (29.5 versus 16.4%, p = .021). CONCLUSIONS: FHR category increased following both CSE and EA. The side effects of maternal hypotension and need for fetal interventions was not different between CSE and EA.

A Pilot Study of Exposure to Nicotine in Human Pregnancy and Maternal and Fetal Testosterone Levels at Birth.

Nicotine exposure in pregnant rats and sheep has shown a more than 50% increase in female fetal testosterone (FFT) levels. Increased testosterone levels have also been linked to infertility, increased anogenital distance (AGD), and reduced second to fourth digit (2D:4D) finger length ratios (FLR). In humans, we hypothesized that maternal total testosterone (MTT) levels would increase in smoking mothers and would cause increased FFT levels, increased AGD, and decreased 2D:4D FLR. This prospective study separated women expecting a female fetus into nonsmoking and smoking cohorts. Maternal cotinine (MC) was tested at 3rd trimester and delivery to assess nicotine exposure. MTT levels were drawn at delivery, and FFT levels were collected from cord blood. The AGD and 2D:4D FLRs were measured at birth. Data were analyzed using parametric and nonparametric tests. The data of 36 smokers and 28 nonsmokers were analyzed. Smoking mothers had higher parity, drug abuse history and were more likely white race. No statistical differences were seen among the primary outcomes of MTT and FFT. MTT was higher among nonsmokers versus smokers (144 versus 107 ng/dL). No correlations were noted between MC levels at delivery, MTT, and FFT levels. No statistical differences were noted among secondary outcomes of AGD and FLR. Although animal studies showed increased FFT levels after nicotine exposure, this was not seen in our human study. Placental differences in animals and humans may be at work. Our pilot study reveals a need for research on the effects of smoking in pregnancy on fetal hormones.

Correlation of glucose concentrations in maternal serum and amniotic fluid in high-risk pregnancies.

OBJECTIVE: We sought to determine whether a correlation exists between maternal serum glucose and amniotic fluid glucose in high-risk pregnancies. STUDY DESIGN: We conducted a prospective cross-sectional study of 60 patients, between 15 and 38 weeks' gestation, undergoing amniocentesis between March 2006 and April 2007. Participants underwent amniocentesis with evaluation of amniotic fluid glucose and maternal finger stick glucose. Data were collected on maternal demographics, gestational age, presence of diabetes or chorioamnionitis, use of betamethasone, and body mass index. Statistical analyses included Spearman rho correlations. RESULTS: A positive correlation was found between maternal serum glucose and amniotic fluid glucose (r = 0.401, P < .01), and amniotic fluid index and diabetes (r = 0.367, P < .05). An inverse correlation was found between amniotic fluid glucose and chorioamnionitis (r = -0.499, P < .01). CONCLUSION: Maternal hyperglycemia directly influences amniotic fluid glucose levels and may result in an elevated amniotic fluid glucose value.

Cannabis Use Based on Urine Drug Screens in Pregnancy and Its Association With Infant Birth Weight.

OBJECTIVES: This study aims to clarify any association between infant birth weight and cannabis use in pregnancy based on urine drug screens. METHODS: A retrospective medical record review of singleton births from August 2013 through December 2014 with available urine drug screens (UDS) at initiation of prenatal care and delivery was conducted at a large tertiary academic referral center. Patients who used drugs other than cannabis were excluded. RESULTS: The prevalence of cannabis use in pregnancies not complicated by use of other drugs as evidenced by tetrahydrocannabinol in the urine of 2173 patients was 22.6%. Infants born to mothers who tested positive for only tetrahydrocannabinol in urine at both presentation for prenatal care and delivery were of lower median birth weight compared with those who tested negative [2925 g (IQR 2522-3265) vs 3235 g (IQR 2900-3591), P = <0.001]. There was no clinically relevant difference in gestational age at birth [39.0 weeks (IQR 37.1-40.0) vs 39.3 weeks (IQR 38.3-40.0), P = 0.012] between those positive for tetrahydrocannabinol (THC) and those who tested negative. Concomitant tobacco use during pregnancy was not noted to impact infant birth weight using the analysis of covariance. Higher perinatal mortality was observed among those who used cannabis with an adjusted odds ratio of 4.2 (95% CI, 1.53-11.49). CONCLUSIONS: Cannabis use is negatively correlated with fetal birth weight (up to 450 g less) in patients who tested positive for THC when compared with those who did not as documented in the urine drug screens. On the basis of these findings, additional patient education and cessation interventions should be explored with regard to cannabis use in pregnancy.

Fetal inflammation associated with minimal acute morbidity in moderate/late preterm infants.

OBJECTIVE: To determine whether exposure to acute chorioamnionitis and fetal inflammation caused short-term adverse outcomes. DESIGN: This is a prospective observational study: subjects were mothers delivering at 32-36 weeks gestation and their preterm infants at a large urban tertiary level III perinatal unit (N=477 infants). Placentae and fetal membranes were scored for acute histological chorioamnionitis based on the Redline criteria. Fetal inflammation was characterised by histological diagnosis of funisitis (umbilical cord inflammation), increased cord blood cytokines measured by ELISA, and activation of the inflammatory cells infiltrating the placenta and fetal membranes measured by immunohistology. Maternal and infant data were collected. RESULTS: Twenty-four per cent of 32-36-week infants were exposed to histological chorioamnionitis and 6.9% had funisitis. Immunostaining for leucocyte subsets showed selective infiltration of the placenta and fetal membranes with activated neutrophils and macrophages with chorioamnionitis. Interleukin (IL) 6, IL-8 and granulocyte colony-stimulating factor were selectively increased in the cord blood of preterm infants with funisitis. Compared with infants without chorioamnionitis, funisitis was associated with increased ventilation support during resuscitation (43.8% vs 15.4%) and more respiratory distress syndrome postnatally (27.3% vs 10.2%) in univariate analysis. However, these associations disappeared after adjusting for prematurity. CONCLUSIONS: Despite fetal exposure to funisitis, increased cord blood cytokines and activated placental inflammatory cells, we could not demonstrate neonatal morbidity specifically attributable to fetal inflammation after adjusting for gestational age in moderate and late preterm infants.

Magnesium sulfate tocolysis and pulmonary edema: the drug or the vehicle?

OBJECTIVES: This study was undertaken to determine the: (1) risk factors for developing pulmonary edema associated with magnesium sulfate (MgSO4) tocolysis; (2) mean latency period to diagnosis; (3) role of maternal transport; and (4) safety of continued therapy. STUDY DESIGN: A total of 150 antenatal patients treated for preterm labor with MgSO4 were identified for this retrospective, case-control study. Cases were compared 1:2 with controls in regard to maternal demographics, MgSO4 concentration and infusion rates, maternal transport status, and maternal net fluid balance. RESULTS: Risk factors for developing pulmonary edema include: greater MgSO4 and intravenous fluid infusion rates, less concentrated MgSO4, infection, multiple gestations, concomitant tocolytics, large positive net fluid balances, and maternal transport. The mean latency period to diagnosis was 1.96 days. Six percent of patients had recurrence if MgSO4 tocolysis was continued. CONCLUSIONS: MgSO4 and intravenous fluid rates are both associated with the development of pulmonary edema. Once appropriately treated, MgSO4 tocolysis can be continued with little risk of recurrence.

Acute fatty liver of pregnancy in 3 tertiary care centers.

OBJECTIVE: The purpose of this study was to determine the demographics, clinical presentation, and maternal and neonatal outcomes in patients who were diagnosed with acute fatty liver of pregnancy over a 10-year period. STUDY DESIGN: This was a multicenter retrospective study of women with the diagnosis of acute fatty liver of pregnancy. Records were reviewed for symptoms, laboratory findings, clinical course, and maternal and perinatal outcomes. RESULTS: Sixteen cases of acute fatty liver of pregnancy were identified. Three of the 16 cases had multiple gestations (18%). Eleven of the 16 cases were diagnosed in the antepartum period, and 5 cases were diagnosed within 4 days after delivery. Nausea and vomiting were the most common symptoms (75%). There were 2 maternal deaths (12.5%) and 3 fetal deaths (15%). CONCLUSION: We recommend that patients with persistent nausea, vomiting, or epigastric pain in the third trimester receive evaluation of liver enzymes, renal function, and a complete blood count to rule out the diagnosis of acute fatty liver of pregnancy.

Delayed postpartum preeclampsia: an experience of 151 cases.

OBJECTIVE: Preeclampsia affects 6% to 8% of pregnancies. There are few data regarding hypertensive disorders that are diagnosed in the postpartum period. Our purpose was to determine the demographics, outcomes, and treatment of this complication. STUDY DESIGN: This was a multicenter retrospective study of women who had received a diagnosis of hypertension/preeclampsia in the postpartum period. Inclusion criteria were readmission of a patient with this diagnosis (