Prediction of neonatal outcome in women with gestational hypertension or mild preeclampsia after 36 weeks of gestation

Background: There is little knowledge about neonatal complications in GH and PE and induction at term, we aim to assess whether they can be predicted from clinical data.

Methods: We used data of the HYPITAT trial and evaluated whether adverse neonatal outcome (Apgar score?<?7, pH?<?7.05, NICU admission) could be predicted from clinical data. Logistic regression, ROC analysis and calibration were used to identify predictors and evaluate the predictive capacity in an antepartum and intrapartum model.

Results: We included 1153 pregnancies, of whom 76 (6.6%) had adverse neonatal outcome. Parity (primipara OR 2.75), BMI (OR 1.06), proteinuria (dipstick +++ OR 2.5), uric acid (OR 1.4) and creatinine (OR 1.02) were independent antepartum predictors; In the intrapartum model, meconium stained amniotic fluid (OR 2.2), temperature (OR 1.8), duration of first stage of labour (OR 1.15), proteinuria (dipstick +++ OR 2.7), creatinine (OR 1.02) and uric acid (OR 1.5) were predictors of adverse neonatal outcome. Both models showed good discrimination (AUC 0.75 and 0.78), but calibration was limited (Hosmer–Lemeshow p?=?0.41, and p?=?0.20).

Conclusions: In women with GH or PE at term, it is difficult to predict neonatal complications, possibly since they are rare in the term pregnancy. However, the identified individual predictors may guide physicians to anticipate requirements for neonatal care.     

Small for gestational age newborns – does pre-recognition make a difference in pregnancy outcome?

Objective: We aimed to evaluate whether pre-recognition of small for gestational age (SGA) at late preterm or term pregnancies, has an impact on pregnancy outcome.

Methods: Retrospective analysis of SGA newborns, stratified to those with suspected or unsuspected IUGR according the sonographic estimated fetal weight (EFW), below the 10th percentile for gestational age (n?=?619), with fetuses not suspected as SGA (EFW ≥10th percentile) preformed up to 7 days prior to delivery (n?=?1770).

Results: SGA was correctly diagnosed prior to delivery in 26% of the fetuses. Women with suspected SGA were delivered earlier (37.9?±?1.7 versus 38.8?±?1.4 weeks, p?<?0.001) and at a lower birth weight (2280?±?321 versus 2454?±?263 grams, p?<?0.001). They also had higher rates of induction of labor (19.1% versus 6.2%, p?<?0.001) and cesarean delivery (29.1% versus 19.8%, p?<?0.001). Fetuses suspected for SGA had higher rate of neonatal adverse outcome, but on multivariate analysis suspected SGA (aOR 0.41, 95% CI 0.20–0.86), birthweight (aOR 0.67, 95% CI 0.5 to ?0.77 for each additional 50?g), gestational age at delivery (aOR 0.63, 95% CI 0.56–0.71 for each additional week) and spontaneous vaginal delivery (aOR 0.88, 95% CI 0.19–3.89) were independently associated with an improved neonatal composite outcome.

Conclusion: Identification of SGA may improve neonatal outcome. However, by itself, it is not an indication for intervention, which may lead to adverse outcome.     

Pregnancy outcome after induction of labor in women with previous cesarean section

Objective: As conflicting data exist concerning the safety of induction of labor (IoL) in women with previous single lower segment cesarean section (CS), we aimed to assess pregnancy outcome following IoL in such patient population.

Methods: All singleton pregnancies with previous single CS which underwent IoL during 2008–2012 were included (study group). Their pregnancy outcome was compared to those pregnancies with previous single CS that admitted with spontaneous onset of labor (control group).

Results: Overall, 1898 pregnancies were eligible, of them, 259 underwent IoL, and 1639 were admitted with spontaneous onset of labor. Parity, gestational age at delivery and birthweight were similar. Women in the study group were more likely to undergo CS mainly due to labor dystocia (8.1 versus 3.7%, p?<?0.01). The rate of CS due to non-reassuring fetal heart rate was similar. No difference was found in the rate of uterine rupture/dehiscence. Short-term neonatal outcome was similar between the groups. On multivariable logistic regression analysis, IoL was not independently associated with uterine rupture (OR 1.33, 95% C.I 0.46–3.84, p?=?0.59).

Conclusion: Our data suggest that IoL in women with one previous low segment CS neither increases the risk of uterine rupture nor adversely affects immediate neonatal outcome.     

Outcome of singleton preterm small for gestational age infants born to mothers with pregnancy-induced hypertension. A population-based study

Background: Pregnancy-induced hypertension (PIH) has been associated with a decreased risk of infant mortality in small for gestational age (SGA) preterm infants.

Objective: To evaluate the influence of PIH on mortality and major neonatal morbidities in singleton preterm SGA infants, in the presence and absence of acute pregnancy complications.

Methods: Population-based observational study of singleton SGA infants, born at 24 to 32 weeks gestation in the period 1995–2010 (n?=?2139). Multivariable logistic regression analyses were used to assess the independent effect of PIH on mortality and neonatal morbidities. Acute pregnancy complications comprised premature labor, premature rupture of membranes >6?h, antepartum hemorrhage and clinical chorioamnionitis.

Results: In the absence of pregnancy complications, the odds ratio (95% confidence interval) for mortality (0.77; 0.50–1.16), survival without severe neurological morbidity (1.14; 0.79–1.65) and survival without bronchopulmonary dysplasia (BPD) (0.85; 0.59–1.21) were similar in the PIH versus no-PIH groups. In the presence of pregnancy complications, mortality (0.76; 0.40–1.44), survival without severe neurological morbidity (1.16; 0.64–2.12) and survival without BPD (1.04; 0.58–1.86) were also similar in the PIH versus no-PIH groups.

Conclusions: PIH was not associated with improved outcome in preterm SGA infants, both in the presence and absence of acute pregnancy complications.     

The effect of placental abruption on the outcome of extremely premature infants

Objective: To determine the effect of placental abruption on the outcome of infants born between 22 and 26 weeks of gestation.

Methods: A retrospective study involving 32 cases of placental abruption. Controls were matched to cases according to gestational age and birth weight. Medical records were reviewed to confirm maternal background and neonatal outcome. We compared characteristics of maternal background and neonatal outcome between the two groups.

Results: There were no significant differences in the incidence of pregnancy-induced hypertension, low maternal fibrinogen (<200?mg/dl), premature rupture of membrane, intrauterine infection, ischemic changes of the placenta, or funisitis between the groups. Non-reassuring fetal heart rate patterns (NRFHRs) during intrapartum were frequently seen in the placental abruption group compared to controls (75% versus 51%, p?=?0.02). However, no differences were found for the incidence of low umbilical artery pH (<7.1), cerebral palsy, or neonatal death. The incidence of chronic lung disease (CLD, 66% versus 43%, p?=?0.04) and hemosiderin deposition on the placenta (16% versus 0%, p?<?0.01) was higher in abruptions compared to controls.

Conclusion: Placental abruption has a risk for the development of NRFHRs and CLD in infants born between 22 and 26 weeks of gestation, but shows no effect on neonatal mortality.     

A comparison of maternal and perinatal outcome between in vitro fertilization and spontaneous dichorionic-diamniotic twin pregnancies

Objective: To compare the maternal and neonatal outcome of dichorionic diamniotic in vitro fertilization (IVF) twin and spontaneous twin pregnancies.

Material and methods: Maternal and fetal data of all consecutive dichorionic-diamniotic twin pregnancies delivered in our institution between January 2009 and May 2015 were abstracted from medical records and pregnancy outcome of IVF twin was compared to spontaneous twin.

Results: Overall 708 twin pregnancies (449 IVF and 259 spontaneous) were included. Women in the IVF group were 2 years older and more frequently nulliparous. The rate of pregnancy induced hypertension and preeclampsia (PIH/PET) was three times higher in the IVF group than in the spontaneous group. The rate of preterm births, before 37 weeks of gestation and the rate of cesarean section were higher in the IVF group. These results were confirmed by multivariate analysis. The neonatal outcome was similar in both the groups except for a lower mean newborn birthweight in the IVF group.

Conclusion: Women with IVF twins are at a significantly higher risk of having preterm births, PIH/PET and cesarean section but there was no significant adverse effect on neonatal outcome except for a lower mean newborn birth weight.     

Cord blood erythropoietin and cord blood nucleated red blood cells for prediction of adverse neonatal outcome associated with maternal obesity in term pregnancy: prospective cohort study

Objective: To determine the adverse pregnancy outcomes associated with maternal pre-pregnancy overweight and obesity and we measure cord blood erythropoietin and NRBC count as indices of hypoxia and predictors of neonatal outcome.

Study design: This prospective cohort study was done in Minia University Hospital, carried out from May 2015 to April 2016. Two hundred and seventy full-term neonates born to mothers of various body mass indices were included. Excluded were neonates with major factors known to be associated with a potential increase in fetal erythropoiesis. Pre-pregnancy maternal BMI was calculated from maternally reported weight and height. Cord blood erythropoietin and nucleated red blood cells were measured.

Results: There is a significant increase of various adverse pregnancy outcomes as cesarean section. Postpartum hemorrhage and macrosomia with the increase of maternal pre-pregnancy BMI. Significant positive correlations between cord blood erythropoietin and nucleated red blood cells with maternal BMI.

Conclusion: The increase in the maternal pre-pregnancy BMI is associated with poor pregnancy outcomes. Cord blood erythropoietin and nucleated red blood cells can predict the poor neonatal outcome.     

Diagnostic value of elevated CXCR4 and CXCL12 in neonatal sepsis

Objective: Neonatal sepsis remains a major cause of morbidity and mortality in newborns. The chemokine CXCL12 and its receptor CXCR4 are now known to play an important role in inflammatory states. However, it is unclear how chemokines respond to late-onset neonatal sepsis.

Methods: Patients were classified into the groups of septic and non-septic ones. Samples of venous blood were obtained from all septic and non-septic newborns at the beginning and within 48–72?h after initiation of treatment. Serum levels of CXCR4 and CXCL12 were measured.

Results: Concentrations of IL-6, CXCR4 and CXCL12 at the time of diagnosis were significantly higher in the septic neonates compared with the non-septic ones. Additionally, there were statistically significant differences in septic neonates between the first and the second levels of IL-6, CXCR4, CXCL12 and I/T ratio. ROC curve analyses revealed that IL-6, CXCR4, CXCL12 and I/T ratio resulted in significant AUC with respect to early identification of septic neonates. Univariate logistic regression analysis showed that increased IL-6, CXCR4 and CXCL12 were strong predictors of neonatal LOS.

Conclusions: Serum CXCR4 and CXCL12 levels increase in septic neonates and that both chemokines decrease within 48–72?h of treatment. Serum concentrations of both chemokines represent promising novel biomarkers for neonatal sepsis.     

Induction of labor in grand multiparous women with previous cesarean delivery: how safe is this?

Objective: To compare the outcome of induced and spontaneous labor in grand multiparous women with one previous lower segment cesarean section (CS), so that the safety of labor induction could be assessed.

Methods: In 102 women (study group), labor was induced and the outcome was compared with 280 women (control group) who went into spontaneous labor. All 382 women were grand multiparous and had one previous CS.

Results: There were no significant difference in oxytocin augmentation, CS, scar dehiscence, fetal birth weight or apgar scores between groups. There was one neonatal death, two still births, one early neonatal death and one congenital malformation in the study group and this was not significant. There was no significant difference in vaginal birth in the study (80.9%) and the control group (83.8%).

Conclusion: In this moderate-sized study, induction of labor may be a safe option in grand multiparous women, if there is no absolute induction for repeating CS.     

Neonatal outcome following new assisted reproductive technology regulations in Turkey – a nationwide multicenter point prevalence study

Objective: In March 2010, a new legislation about assisted reproductive technology (ART) activities, favoring single embryo transfer, was introduced in Turkey. Consequences of new regulations on neonatal outcome have not been evaluated in multicenter studies yet. In this study, our aim was to evaluate neonatal outcome of infants from medically assisted reproduction (MAR) pregnancies in the post-legislation era.

Methods: A point prevalence study was conducted at 51 centers in Turkey on 1 April 2013. Data about fertility treatments and neonatal characteristics were evaluated for “live births” (Group 1) and “patients being cared in the NICU” (Group 2).

Results: Seventeen (4%) of 420 infants in group 1, and 89 (8.1%) of 1094 infants in group 2 were born after MAR pregnancies. The ratio of multiple births in MAR pregnancies was still very high as 47.1% for group 1, 69.1% for group 2 infants. MAR babies constituted 9.9% of infants in Level 3 NICUs and 7.6% infants in Level 2 NICUs. MAR was associated with increased risk of multiple births and prematurity.

Conclusions: After the new legislation, multiple birth rates are still high in MAR pregnancies, resulting in unfavorable neonatal outcomes. Efforts to decrease multiple birth rates should be encouraged.     

Neonatal morphine in extremely and very preterm neonates: its effect on the developing brain – a review

Objective: Preterm infants requiring intensive care experience a large number of stressful and painful procedures. Management of stress and pain is therefore an important issue. This review provides an overview of the research on the use of morphine and its neurodevelopmental effects on this vulnerable group of neonates.

Methods: A structural literature search of both experimental and clinical data has been done using an electronic database (PubMed), but also relevant reference lists and related articles were used.

Results: A total of 39 sources were considered relevant for this review to elucidate the effects of morphine on the developing brain. The results showed that both animal experimental and clinical data displayed conflicting results on the effects of neonatal morphine on neurodevelopmental outcome. However, in contrast to specific short-term neurological outcomes long-term neurodevelopmental outcome does not seem to be adversely affected by morphine.

Conclusion: After a careful review of the literature, no definite conclusions concerning the effects of neonatal morphine on the long-term neurodevelopmental outcome in extremely premature neonates can be drawn. More prospectively designed trials should be conducted using reliable and validated pain assessment scores to evaluate effects of morphine on long-term neurodevelopmental outcome to demonstrate a beneficial or adverse effect of morphine in preterm infants.     

Magnesium sulfate for neuroprotection in the setting of chorioamnionitis

Purpose: We examined the effects of magnesium on premature neonatal outcomes complicated by chorioamnionitis.

Materials and methods: We conducted a secondary analysis of data from the BEAM Trial, an RCT to determine if antenatal magnesium decreases the incidence of CP in preterm birth. We compared the effect of magnesium sulfate by the presence or absence of chorioamnionitis. Outcomes examined include CP, IVH, NEC, BPD, and assessments of mental and motor disability. Logistic regression was used to estimate adjusted odds ratios of each outcome.

Results: About 1944 women were included in this analysis of which 228 were diagnosed with chorioamnionitis. Demographic characteristics were similar between women randomized to receive magnesium or placebo. Magnesium therapy demonstrated no significant reduction in CP in the presence of chorioamnionitis (OR 0.76, CI: 0.19–2.76) but does demonstrate benefit in the absence of chorioamnionitis (OR 0.52, CI: 0.31–0.86).

Conclusions: Antenatal magnesium did not show a clear neuroprotective effect in the setting of chorioamnionitis.     

Cystatin C in newborns: a promising renal biomarker in search for standardization and validation

Objective: Neonatologists still commonly use creatinine as a proxy for renal clearance, despite issues related to neonatal (patho)physiology and methodology (assay variability). Cystatin C (CysC) has been suggested to be a more reliable biomarker, but assay related differences have also been reported in children and adults. We are unaware of any review on the assay related impact on CysC reference values in newborns.

Methods: A structured literature search was performed on published CysC values in (pre)term neonates.

Results: The extensive range (>5-fold) in serum CysC observations in neonates in part relates to the fact that CysC concentrations are higher at birth with subsequent decrease and that CysC concentrations are higher in preterm compared to term neonates. The CysC assay matters while disease characteristics also affect CysC values, but not always in the predicted direction.

Conclusions: Similar to creatinine, the extensive CysC range in neonates is only in part explained by renal (patho)physiology. Its applicability in neonatal medicine can be further improved by use of assay specific reference values, adapted to neonatal renal physiology (e.g. weight, age) and should be compared to a gold standard such as inulin clearance.     

Perinatal antibiotic exposure of neonates in Canada and associated risk factors: a population-based study

Objective: To describe neonatal antibiotic exposures occurring immediately before and after birth and their associated risk factors.

Methods: A retrospective review of the hospital charts of 449 mother–neonate pairs enrolled in the Canadian Healthy Infant Longitudinal Development national birth-cohort study was conducted at two tertiary hospitals and one rural hospital in Manitoba, Canada. The main outcome measures included the following: maternal and neonatal antibiotic use during the perinatal period; indications for antibiotic use, including suspected neonatal sepsis, maternal group B Streptococcus (GBS), premature rupture of membranes and caesarean-section; maternal health status, focusing on gestational hypertension, gestational diabetes, obesity and primigravida pregnancies.

Results: During the perinatal period, 45.0% of neonates were exposed to antibiotics. Intravenous penicillin G (17%) and cefazolin (16%) were the most commonly administered intrapartum antibiotics. Colonization with GBS was confirmed in 21.2% of women and treated with antibiotics in 86% of cases. Overweight women and women with hypertension were significantly more likely to receive intrapartum antibiotics for caesarean section or GBS prophylaxis. Antibiotic treatment of the neonate was highest following emergency caesarean section (12%) or unknown maternal GBS status (20%).

Conclusions: Neonates in Canada are routinely exposed to antibiotics during the perinatal period.     

Association between maternal HBsAg carrier status and neonatal adverse outcomes: meta-analysis

Objective: We conducted a meta-analysis to evaluate whether maternal hepatitis B virus (HBV) carrier status increases the risk of neonatal complications.

Methods: Publications addressing the association between maternal HBV carrier status and neonatal outcomes were selected from the PubMed, EMBASE, Web of Science, Cochrane Library and China National Knowledge Infrastructure. Publication bias and heterogeneity across studies were evaluated and summary odds ratios, weighted mean difference or standardized mean difference and 95% confidence intervals were calculated and compared between groups.

Results: Eighteen studies and 7600 pregnant HBV carriers were selected for analyses. A statistically association with maternal HBV carrier status was demonstrated for premature birth and asphyxia, with no difference found among perinatal mortality, gestational age, small for gestational age, large for gestational age, birth weight, low birth weight, macrosomia, Apgar sore at 1?min, jaundice and congenital anomaly. Heterogeneity across studies was found, and no publication bias was detected.

Conclusion: Our analysis suggests that maternal hepatitis B carrier status is significantly associated with premature birth and asphyxia. Large-scale prospective studies are still warranted.     

ß-hCG and prediction of therapeutic success in ectopic pregnancies treated with methotrexate,results from a prospective observational study

Objective: To evaluate the diagnostic accuracy of different beta-human chorionic gonadotrophin (ß-hCG) levels measurement, for predicting success of medical treatment in cases diagnosed as tubal ectopic pregnancy (TEP).

Design: Five-year prospective observational study.

Setting: Prenatal Diagnosis Unit, Vall d'Hebron University Hospital – Barcelona.

Patients: TEP cases fulfilling criteria for medical treatment with Methotrexate.

Interventions: ß-hCG levels were measured on d 0, 4 and 7 of treatment. Results were compared by non-parametrical tests. A ROC curve was plotted to define cut-off points. Diagnostic accuracy of the different measurements was evaluated.

Main outcome measure: Failure of treatment defined as need for surgical treatment or persistence of high ß-HCG levels despite treatment.

Results: 126 women were diagnosed as TEP, eligible for medical treatment. There were no differences in parity, age, previous TEP, or adnexal mass size. Success rate was 88%. ß-HCG decreased significantly more, between days 0–7 and 4–7, in the successful cases. LR for success prediction was 6.2 and 7.8 for ß-HCG levels at days 4 and 7 respectively, 4.02 and 2.47 for decrement between days 0–7 (25%) and 4–7 (20%), respectively.

Conclusion: ß-hCG cutoff values have a potential for predicting a successful medical treatment of TEP.     

Maternal risk factors for neonatal necrotizing enterocolitis

Objective: This study aimed to investigate the relationship between maternal hypertensive disease and other risk factors and the neonatal development of necrotizing enterocolitis (NEC).

Methods: This was a retrospective case–control study of infants with NEC from 2008 to 2012. The primary exposure of interest was maternal hypertensive disease, which has been hypothesized to put infants at risk for NEC. Other variables collected included demographics, pregnancy complications, medications and neonatal hospital course. Data were abstracted from medical records.

Results: Twenty-eight cases of singleton neonates with NEC and 81 matched controls were identified and analyzed. There was no significant difference in the primary outcome. Fetuses with an antenatal diagnosis of growth restriction were more likely to develop NEC (p?=?0.008). Infants with NEC had lower median birth weight than infants without NEC (p?=?0.009). Infants with NEC had more late-onset sepsis (p?=?0.01) and mortality before discharge (p?=?0.001).

Conclusions: The factors identified by this case–control study that increased the risk of neonatal NEC included intrauterine growth restriction and lower neonatal birth weight. The primary exposure, hypertensive disease, did not show a significantly increased risk of neonatal NEC; however, there was a nearly two-fold difference observed. Our study was underpowered to detect the observed difference.     

Ultrasound assessment of fetal head circumference at the onset of labor as a predictor of operative delivery

Objective: This study sought to determine whether ultrasound assessment of fetal head circumference (FHC) at the onset of labor can predict the likelihood of operative delivery.

Methods: We performed a prospective cohort study of 200 nulliparous women with singleton, cephalic, term pregnancies in an Irish Maternity Hospital. Transabdominal ultrasound assessment of FHC was performed when spontaneous labor was diagnosed or immediately prior to induction. Odds ratios for operative delivery (instrumental delivery or cesarean section) and maternal and neonatal morbidity were calculated using logistic regression with FHC categorized at a ≥350-mm cut-off (90th percentile).

Results: Ultrasound assessment of FHC at the onset of labor was highly correlated with post-delivery neonatal head circumference (NHC) (Pearson’s correlation coefficient 0.74), suggesting that it can be measured reliably. FHC ≥350?mm was associated with more than twice the risk of any operative delivery (OR 2.5, 95% CI 1.0–6.2) and a two-fold increased risk of cesarean section for dystocia (OR 2.0, 95% CI 1.0–4.3). Differences in maternal and neonatal morbidity were not statistically significant.

Conclusion: These preliminary data suggest that ultrasound assessment of FHC at the onset of labor may be useful in identifying women at greater risk of intrapartum intervention and warrant further research.     

Fetal intracranial immature teratoma: presentation of a case and a systematic review of the literature

Objectives: To describe a case diagnosed with intracranial teratoma in week 32 of gestation, as well as review of the literature in order to discern the appropriate treatment method and general prognosis of this anomaly.

Methods: A literature search was performed on the prenatal diagnosis of congenital intracranial teratomas in MEDLINE, EMBASE, Cochrane library data bases. Evaluated in this review are parameters such as time of prenatal diagnosis, associated pathology, size of tumors, method of terminating pregnancy, perinatal outcome and histological study of the tumor.

Results: A total of 49 cases were found, of which 12 were finished gestation, 28 cesarean section was performed and only nine had vaginal delivery. All died in the neonatal period except in three cases with intrauterine death after diagnosis.

Conclusion: As the incidence of intracranial immature teratomas is very low and the prognosis is poor, their prenatal diagnosis and obstetric management present a great challenge for the planning of a follow-up and treatment of the disease in accordance with the preferences of the parents.     

Continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) of rapid-acting insulin analogues and detemir in type 1 diabetic (T1D) pregnant women

Objective: To compare glycemic control, maternal-neonatal outcomes and fetal fat body mass growth of type 1 diabetic pregnant women treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) with the long-acting insulin analogue detemir as basal insulin.

Methods: Retrospective study of 53 women, attending the Unit of Prenatal Medicine of Careggi University Hospital, Florence, from 2009 to 2012: 35 treated with CSII, 18 with MDI-detemir. Each woman performed daily blood glucose self-monitoring, had an individualized nutritional therapy, weekly prenatal visits and ultrasound scans (US) according to the Tuscan guidelines. US were also performed every two weeks from 28 to 38 weeks of gestation to assess fetal fat body mass growth. Student’s t-test and Chi-square test were performed to compare the groups’ results.

Results: No significant differences were observed in metabolic control, in any maternal and neonatal outcome nor fetal fat body mass growth for either group. The MDI group needed higher daily doses of insulin (MDI: 1.00?±?0.32 UI/kg versus CSII: 0.75?±?0.29 UI/kg, p?=?0.007) to reach results comparable to the CSII group.

Conclusions: MDI therapy with detemir is a safe and effective alternative, with a good benefit–cost ratio compared to insulin pumps.