Intra-Amniotic Inflammation or Infection: Suspected and Confirmed Diagnosis of "Triple I" at Term.

Chorioamnionitis (CA) at term of pregnancy can have an infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (intrauterine inflammation, infection, or both, TI) has been proposed to reduce the overdiagnosis of infection and neonatal overtreatment. The aim of this study is to identify clinical and histological variables that could predict adverse outcomes when TI is suspected and/or confirmed. This retrospective cohort study included 404 pregnancies (gestational age ≥ 37 weeks) that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to the NICHD definition of 2015, and it could be confirmed (TI+) or not confirmed (TI-) via histological examination. Signs of infection/inflammation that did not conform to the definition of TI were classified as "clinical suspicion" and could be supported (CS+) or not supported (CS-) by histology. Cases of histological chorioamnionitis (HCA) without clinical manifestation represented a fifth group. Whole placental involvement (WPLI) was defined as a histological inflammation involving the maternal and fetal sides. There were 113 TI+, 30 TI-, 186 CS+, 35 CS-, and 40 isolated HCA cases. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). Compared with CS+, TI+ was more predictive of CNO (p = 0.001), CMO (p < 0.001), and WPLI (p = 0.005). WPLI was related both to CNO (p < 0.001) and to CMO (p = 0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p = 0.001) and by WPLI (OR 2.23; p = 0.001). Compared with CS, TI is a better predictor of CNO and can be useful for the identification of newborns at risk.

Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study).

BACKGROUND: Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population. METHODS: The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing. RESULTS: Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was .19% (95% confidence interval [CI]: .11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio [OR]: 7.2; 95% CI: 1.7-32.2; P = .037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P = .003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled. CONCLUSIONS: Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT03973359).

Neonatal outcomes and risk of neonatal sepsis in an expectantly managed cohort of late preterm prelabor rupture of membranes.

OBJECTIVE: Expectant management in patients with prelabor preterm rupture of membranes between between 340/7 and 36 6/7 weeks (late preterm pPROM or LpPROM) has been shown to decrease the burden of prematurity, when compared to immediate delivery. As the severity of prematurity depends on gestational age (GA) at PROM, and PROM to delivery interval, we first investigated how such variables affect neonatal outcomes (NO). Second, we assessed the risk of neonatal sepsis. STUDY DESIGN: retrospective cohort study on neonatal morbidity among singleton infants born to expectantly managed mothers with LpPROM in five hospitals affiliated with three Italian academic institutions. The primary NO was a composite of neonatal death, non-invasive (cPAP) or invasive (mechanical ventilation) respiratory support, hypoglycemia (< 44 mg/dl needing therapy), newborn sepsis, confirmed seizures, stroke, intraventricular hemorrhage (IVH), basal nuclei anomalies, cardiopulmonary resuscitation, umbilical-cord-blood arterial pH < 7.0 or base excess < -12.5, and prolonged hospitalization (≥ 5 days). Univariate analysis described differences in the population according to GA at delivery. Multivariate logistic regression was then used to investigate the effects of GA at PROM, and PROM to delivery interval on the NO. RESULTS: 258/606 (42.6 %) women with LpPROM were expectantly managed, as they did not deliver within the first 24 h. The median latency duration was 2 (95 %CI 1-3) days, having no effect on neonatal morbidity on multivariate analysis. Multivariate analysis also showed increased risks of adverse NO among PROM at 34 (OR 2.3 95 %CI 1.03-5.1) but not at 35 weeks when compared to 36 weeks, and among women receiving antenatal corticosteroids (OR 3.6 95 %CI 1.3-9.7), while antibiotic treatment showed a non-significant protective effect (OR 0.2 95 %CI 0.04-1.02). Prevalence of neonatal sepsis was 0.8 % (2/258) CONCLUSION: Expectant management of LpPROM should be encouraged especially between 34+0 and 34+6 weeks', when the burden of prematurity is the greatest. Antibiotics may have beneficial effects, while careful consideration should be given to antenatal corticosteroids until future studies specifically address LpPROM.

Operative vacuum vaginal delivery: effect of compliance with recommended checklist.

PURPOSE: Even if the prerequisites and the technique of vacuum extraction are largely established, the role of a checklist in this field has not been tested. To evaluate the role of a checklist implementation on the compliance with the recommended rules in operative vacuum vaginal delivery (OVD) and on maternal and perinatal outcomes. MATERIALS AND METHODS: Retrospective cohort study on OVD between January 2012 and December 2015 at two hospitals with a tradition of teaching of OVD. A checklist for OVD was introduced in 2014. Three rules had to be recorded: fetal head station and position determination, no more than four tractions, and no more than three cup applications. Adverse maternal outcomes included third- and fourth-degree perineal tears. Adverse neonatal outcome included asphyxia, need for neonatal resuscitation, NICU admission, major head injuries, scalp injuries, and bone or brachial plexus injuries. RESULTS: Introduction of a checklist for OVD resulted in an increase in the compliance with the rules (83.3 versus 62.8%, p < .001). Cases in which the rules were respected had lower incidence of third- and fourth-degree perineal lacerations after controlling for episiotomy, nulliparity, and indication for OVD (OR = 0.4, 95% CI 0.18-0.89), but similar rates of failure of OVD (2.1 versus 2.2%, p = 1) and adverse neonatal outcome (10.8 versus 11.7%, p=.71). CONCLUSION: Knowledge and documented compliance with a checklist of recommended rules in OVD may assist in achieving a lower rate of severe perineal and anal sphincter injury but does not alter the success of the procedure or neonatal outcome.

Umbilical cord management strategies at cesarean section.

AIM: To evaluate the effect of different strategies to improve placental transfusion in cesarean section (CS). METHODS: Retrospective analysis of all singleton term pregnancies that underwent CS over 6 months. Delayed umbilical cord clamping (dUCC) was defined as one done at least 60 s after birth. Umbilical cord milking (UCM) was an option when waiting 60 s was deemed unsafe. The two strategies were compared against early (<60 s) umbilical cord clamping (eUCC) without milking. Neonatal hematocrit (Hct) at 48 h was the main outcome variable. RESULTS: Of the 223 CS in the cohort, 100 were performed in labor and 123 were elective. dUCC was performed in 137, eUCC without milking in 53 and UCM in 33 cases. Neonatal Hct was higher in CS carried out in labor versus in elective CS (59.76% ± 6.17 vs 56.91% ± 5.95, P = 0.001). At multivariate analysis, CS performed in labor (coefficient [coeff.] 3.44, confidence interval [CI] 1.75-5.13, P < 0.001), UCM (coeff. 3.88, CI 1.61-6.14, P = 0.001) and birth weight (coeff. -0.003, CI -0.005 to -0.001, P = 0.001) were the only variables independently associated with neonatal Hct. In elective CS, UCM led to higher neonatal Hct (61.5% ± 5.5) compared to eUCC without milking (55.1% ± 5.5) and dUCC (56.4% ± 5.7, P = 0.001), while in CS performed in labor there were no significant differences among the placental transfusion strategies. CONCLUSION: In term CS, neonatal Hct is significantly higher when the CS is performed in labor or with UCM. In elective CS, UCM could be a valid option to favor placental transfusion.

Risk factors for cerebral palsy in PPROM and preterm delivery with intact membranes (.).

OBJECTIVE: Gestational age (GA) at delivery and spontaneous prematurity are independent risk factors for cerebral palsy (CP). The aim of this study is to investigate perinatal risk factors for CP in spontaneous preterm delivery. METHODS: A retrospective cohort study of all single pregnancies complicated by spontaneous preterm labor (PTL) or PPROM with delivery at <34 weeks from January 2006 to December 2012 was performed. We compared demographic, obstetric, neonatal, and placental histology variables in cases of spontaneous preterm birth in reference to the development of CP. Statistical analysis included chi-square, one-way ANOVA and logistic regression analysis. p < 0.05 was considered significant. RESULTS: Two hundred sixty-one women were included for this study. Of 249 survivors, 5 babies died during the first year of life, 52 did not fulfill the inclusion criteria for neurologic follow-up, and 24 were lost to follow up. Thus 168 infants in the study cohort underwent neurologic follow-up. We observed 26 cases of CP. Factors related to CP were lower GA at PROM (p = 0.007) and longer latency from PPROM to delivery (p = 0.002) in the PPROM group, lower GA at delivery (p < 0.001) and presence of funisitis (p <0.001) in the PTL group. CONCLUSIONS: GA at membrane rupture in PPROM and GA at delivery in PTL are significantly associated with CP. A process leading to neurological damage may be initiated at the moment of membranes rupture in cases of PPROM and at the time of PTL in the group with intact membranes.

Preterm labor: approach to decreasing complications of prematurity.

Obstetricians play a relevant role in minimizing neonatal morbidity and mortality for women in preterm labor. Tocolytic agents can delay preterm birth for at least 2 days, thus allowing the administration of antenatal corticosteroid and in-utero transfer to appropriate neonatal health care settings, interventions that reduce neonatal mortality and morbidity. Antibiotics besides group B streptococcus prophylaxis are not indicated. The benefit/risk ratio of amniocentesis has not been assessed yet. Magnesium sulfate significantly reduces the risk of cerebral palsy. Cesarean delivery benefits fetuses in breech presentation and those severely growth restricted at <34 weeks. In preterm infants delayed clamping is associated with significant benefits.

Non-invasively collected amniotic fluid as a source of possible biomarkers for premature rupture of membranes investigated by proteomic approach.

PURPOSE: Preterm delivery is one of the main causes of perinatal morbidity and mortality and it accounts for 75 % of perinatal mortality and more than half of the long-term morbidity. We applied a proteomic approach based on mass spectrometry (MS) for biomarkers discovery of preterm premature rupture of membranes (pPROM) by investigating amniotic fluid (AF) invasively and non-invasively collected. METHODS: Amniotic fluid was obtained from vagina of women with pPROM (group 1), PROM at term (group 2) and by genetic amniocentesis (group 3). Pre-fractionated AF proteome was analyzed through matrix assisted laser desorption ionization-time of flight (MALDI-TOF) MS. The characterization of proteins/peptides of interest was obtained by high performance liquid chromatography-electrospray tandem MS. RESULTS: Three peptides overexpressed in pPROM and able to discriminate the groups 1 and 2 were detected. One peptide was identified as the fragment Gly452LAVPDGPLGLPPKPro466 of the protein KIAA1522, expressed by fetal brain and liver. This peptide was overexpressed in a patient of the group 3, completely asymptomatic at the time of the amniocentesis, who later developed pPROM. CONCLUSION: Amniotic fluid invasively and non-invasively collected can be analyzed by MALDI-TOF MS to obtain proteomic profiles. Proteomic analysis identified a peptide with promising diagnostic capability for pPROM.

Infants weighing <1500 g: better born too small or too soon?

OBJECTIVE: To evaluate the influence of intrauterine growth on intact neurological outcome at 12 to 24 months in a cohort of infants weighing <1500 g at birth. STUDY DESIGN: This retrospective study was conducted in the Department of Obstetrics and Gynecology, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. Perinatal variables were correlated with occurrence of composite adverse outcome, including neonatal death or adverse neurodevelopmental outcome (ANDO), at 12 to 24 months' follow-up, in 240 consecutive very low-birth-weight (VLBW) neonates prenatally classified as growth restricted (IUGR; n = 100) or appropriate for gestational age (n = 140). RESULTS: Among the 214 surviving neonates, neurological follow-up was available in 163. ANDO was present in 46 children (28%). At multivariate analysis, only gestational age at delivery was independently related to the composite outcome (p < 0.001, odds ratio = 0.69, 95% confidence interval 0.59, 0.81), whereas diagnosis of IUGR was not. CONCLUSION: Only gestational age at delivery was significantly associated with composite adverse outcome in VLBW preterm infants.

Can placental histology establish the timing of meconium passage during labor?

OBJECTIVE: To evaluate the relation between duration of placental exposure to recently passed meconium in vivo and histological evidence of meconium uptake by macrophages. DESIGN: Retrospective cohort. SETTING: University hospital. POPULATION: A total of 44 term deliveries of singleton infants with moderate or thick meconium had placental examination and documented timing of meconium appearance after membrane rupture. METHODS: Placentas were examined to assess the extent of meconium uptake by macrophages based on location in the amniochorionic membranes, chorionic plate and umbilical cord, and the intensity of uptake, based on the number of macrophages per field. An arbitrary score of severity of uptake was also created by multiplying the intensity of meconium uptake (number of meconium-laden macrophages) by the extent in the three placental areas. Twenty cases of singleton term pregnancy with clear amniotic fluid throughout labor and at delivery were included as negative controls. MAIN OUTCOME MEASURES: Relation between interval of meconium exposure in vivo and uptake by macrophages. RESULTS: The median interval from meconium appearance to delivery was 95 minutes (range 10-510 minutes). The median score of severity of meconium uptake was significantly higher than in the negative controls. There was no correlation between the interval of meconium appearance to delivery and score of severity of meconium uptake (p=0.76). Inflammatory lesions were present in 12 (27%) of 44 cases and vascular lesions in 11 (25%) of 44. CONCLUSIONS: Duration of placental exposure to meconium in vivo was not related to meconium uptake by macrophages where exposure was <8.5 hours.

Variability in rate of cervical dilation in nulliparous women at term.

BACKGROUND: Cervical dilatation is commonly documented on a partogram indicating the expected rate of progress of labor. Although deviations from such a line can be used to indicate abnormal progress, what constitutes the "normal" rate of cervical dilation is still largely unknown. The objectives of this study were to assess the variability of the rate of cervical dilation in nulliparous women and to determine whether the rate of labor was independent of dilation on admission. METHODS: We analyzed a cohort of consecutive nulliparous women with spontaneous labor at term and singleton fetuses in cephalic presentation. Exclusion criteria were gestational age less than 37 weeks, induction of labor, or the presence of a uterine scar. Management of labor was standardized using set protocols of care. Active labor was diagnosed as regular contractions every 10 minutes or less, lasting more than 40 seconds, with cervical effacement more than 80 percent and dilation of 2 cm. Vaginal examinations were performed by a dedicated midwife every 2 hours. Amniotomy was performed for slow progress or arrest of dilation over 2 hours. Oxytocin was administered for arrest of cervical dilation for 2 hours with membranes ruptured. Data pertaining to cases ending in cesarean delivery were included up to the time of cesarean section. RESULTS: The study sample comprised 1,119 women at 39.7 ± 1.1 weeks with an average duration of labor of 4.1 ± 2.4 hours. The rate of oxytocin use was 27 percent and of epidural analgesia 5 percent. The rate of oxytocin use was inversely related to cervical dilation on admission. Cesarean delivery was performed in 6 percent of women. Duration of labor at each centimeter of cervical dilation on admission showed a broad distribution (e.g., at 4 cm: median = 5.5, range: 0.8-12.5 hr). The rate of labor progression (expressed as the slope of the dilation-vs-time curve) was approximately 1.5 cm/hr, and it was essentially independent of cervical dilation on admission (r = 0.034, p = 0.267). A deceleration phase seemed to be present toward the end of the active phase of labor (approximately 9 cm). CONCLUSION: In our setting, the rate of labor in nulliparous women at term was highly variable, and it did not appear to be affected by cervical dilation on admission.

A case report of a successful monochorionic diamniotic twin pregnancy in a patient affected by sickle cell disease treated with erythrocytapheresis.

We describe a monochorionic diamniotic twin pregnancy in a 28-year-old woman with a severe form of sickle cell disease periodically treated with erythrocytapheresis (EA). During this high risk pregnancy, two sessions of EA were performed without complications, and pain control and fetal growth were optimal. Delivery was carried out by emergency cesarean section at 29(+3) weeks' gestation due to initial fetal distress following twin-to-twin transfusion. There were no significant complications for the newborn twins and the post-partum course was regular. The patient underwent a further EA 7 weeks after surgery. Close collaboration between obstetricians and hematologists with careful maternal-fetal monitoring and prophylactic EA during pregnancy led to a favorable outcome despite a low maternal body weight, a twin pregnancy, and a severe form of sickle cell disease.

Antepartum and intrapartum risk factors for neonatal encephalopathy at term.

We investigated antepartum and intrapartum risk factors for neonatal encephalopathy (NE) in term infants. We performed a case-controlled study in which characteristics of singleton term infants who developed NE from 1993 to 2003 were compared with those of randomly selected controls. Antenatal risk factors (including obesity, diabetes, thyroid dysfunction, previous cesarean delivery, preeclampsia, fetal growth restriction, abnormal amniotic fluid volume, and abnormal fetal heart rate [FHR] tracing before labor) and intrapartum risk factors (acute intrapartum sentinel events and other risk factors like suspicious or ominous FHR tracing and clinical chorioamnionitis) were related to occurrence of NE. From the study cohort of 30,580 infants, 27 (0.09%) developed NE and were compared with 100 controls. Neonates with encephalopathy had more frequent antepartum (74% versus 18%, P < 0.001) and intrapartum (67% versus 19%, P < 0.001) risk factors, including acute intrapartum events (33% versus 2%, P < 0.001), than controls. On the whole, 26% of cases of NE had only antepartum risk factors, 22% had only intrapartum risk factors, and 44% had a combination of the two. In 2/27 (7%) cases, no risk factors were recognizable. In conclusion, 44% of cases of NE following term deliveries can be attributed to a combination of antepartum and intrapartum variables.

Prediction of duration of active labor in nulliparous women at term.

We have assessed the independent predictors of duration of active labor in nulliparous women at term. Using a cohort of 1067 nulliparae in spontaneous labor at > 37.0 weeks with singleton fetuses in vertex presentation, multivariate analysis was used to identify independent predictors of duration of active labor. Duration of active labor was 4.1 +/- 2.4 hours. Stepwise linear regression selected 10 independent predictors of duration of active labor: gestational age at delivery ( P < 0.001), race ( P = 0.014), obstetric risk factors ( P = 0.022), amniotomy ( P < 0.001), fundal height ( P = 0.005), cervical dilation on admission ( P < 0.001), frequency of contractions ( P < 0.001), station of presenting part ( P < 0.001), oxytocin ( P < 0.001), and epidural use ( P < 0.001). A prediction formula incorporating the 10 predictors accounted for 51% of the total variance of the observed duration of active labor. Ten variables are independent predictors of duration of active labor; when incorporated in a prediction formula they account for > 50% of the variability of duration of labor in nulliparous women.

Predictors of umbilical artery acidosis in preterm delivery.

OBJECTIVE: The purpose of this study was to investigate the significance of preterm acidosis and its risk factors. STUDY DESIGN: From a cohort of 786 consecutive singleton neonates who were born after spontaneous or iatrogenic preterm delivery at 24.0-33.6 weeks of gestation from January 1993 to December 2005 with an evaluation of umbilical artery pH at delivery, we extracted demographic, obstetric, neonatal, and placental histologic variables and related them to umbilical artery evidence of fetal acidemia, which was defined as pH <7.10. Excluded were stillbirths and neonates with major congenital anomalies. Fetal distress was defined as nonreassuring fetal hearth rate tracing or biophysical profile or appearance of thick meconium at delivery. Statistical analysis included 1-way analysis of variance and logistic regression with a probability value of <.05 considered significant. RESULTS: Neonates with umbilical cord evidence of acidosis (n = 34) were born more frequently after abruption (P < .001), fetal distress (P < .001), and by cesarean delivery (P < .04) and were born less frequently after a complete course of corticosteroids (P = .03) and labor (P = .05) than nonacidotic babies (n = 752). Acute inflammatory lesions at placental histologic evaluation were less frequent (P = .049), and placental vascular lesions were more common in acidotic than in nonacidotic preterm neonates (P = .039). Logistic regression analysis demonstrated that cord acidosis was associated independently with the occurrence of abruptio placentae (odds ratio, 7.3; 95% CI, 2.9, 18.8), fetal distress (odds ratio, 12.0; 95% CI, 4.9, 18.3), and vascular placental lesions (odds ratio, 2.8; 95% CI, 1.2, 6.8) CONCLUSION: In preterm infants, umbilical artery acidosis is significantly more common in the presence of placental abruption, fetal distress, and histologic evidence of placental vascular disease.