Volume 46, Issue 2

Abstract: Fetal cardiac tumors are rare and usually benign. While echocardiography is a reliable technique for diagnosing fetal cardiac tumors, their definitive diagnosis relies on pathological examination. The strategies used to manage fetal cardiac tumors are challenging. A good clinical result is their complete regression during pregnancy or shortly after birth, as often occurs with cardiac rhabdomyomas. Moreover, the fetal prognosis depends on the nature of the tumors, namely, their location, size, number and associated complications. The active treatment options for symptomatic fetuses depend on the fetal status and may include fetal open surgery, postnatal tumor resection with or without the bridge of intrauterine pericardiocentesis, and thoracoamniotic shunting. The ex utero intrapartum treatment procedure provides an alternative technique for performing fetal open surgery and has shown promising preliminary results in selected cases, but is invasive for both the mother and fetus.

Objective: The objective of this study is to determine whether the amniotic fluid (AF) concentration of soluble CXCR3 and its ligands CXCL9 and CXCL10 changes in patients whose placentas show evidence of chronic chorioamnionitis or other placental lesions consistent with maternal anti-fetal rejection. Methods: This retrospective case-control study included 425 women with (1) preterm delivery (n=92); (2) term in labor (n=68); and (3) term not in labor (n=265). Amniotic fluid CXCR3, CXCL9 and CXCL10 concentrations were determined by ELISA. Results: (1) Amniotic fluid concentrations of CXCR3 and its ligands CXCL9 and CXCL10 are higher in patients with preterm labor and maternal anti-fetal rejection lesions than in those without these lesions [CXCR3: preterm labor and delivery with maternal anti-fetal rejection placental lesions (median, 17.24 ng/mL; IQR, 6.79–26.68) vs. preterm labor and delivery without these placental lesions (median 8.79 ng/mL; IQR, 4.98–14.7; P=0.028)]; (2) patients with preterm labor and chronic chorioamnionitis had higher AF concentrations of CXCL9 and CXCL10, but not CXCR3, than those without this lesion [CXCR3: preterm labor with chronic chorioamnionitis (median, 17.02 ng/mL; IQR, 5.57–26.68) vs. preterm labor without chronic chorioamnionitis (median, 10.37 ng/mL; IQR 5.01–17.81; P=0.283)]; (3) patients with preterm labor had a significantly higher AF concentration of CXCR3 than those in labor at term regardless of the presence or absence of placental lesions. Conclusion: Our findings support a role for maternal anti-fetal rejection in a subset of patients with preterm labor.

Abstract: A multifaceted intervention at all six obstetric units in the Stockholm Health Region was performed in 2008–2011 in order to increase safety for the newborn infants. Case-controlled criterion-based reviews of care processes during labor and delivery have been used to assess factors associated with suboptimal care during labor and delivery. Categories of increased risk of adverse outcome during labor and delivery were defined. Cases with low Apgar scores and healthy controls were scrutinized and compared to data from a study with an identical design performed before the intervention. The risk of suboptimal care increased twice among controls and three times among cases when reviewing specific criteria after a multifaceted intervention. There are still gaps in care processes that need attention. Improving guidelines is important but not enough alone, and the management of fetal surveillance needs further improvement. The complexity of reviewing care processes using criterion-based research methodology is highlighted.

Objective: To identify the prevalence of and to determine the risk factors for developing a fear of childbirth (tokophobia). Methods: We evaluated 191 pregnant women during Parenting and Childbirth Classes. Participants were approached when attending Parenting and Childbirth Classes between June 2014 and September 2014 and were asked to complete several questionnaires related to depression (CES-D), anxiety (STAI X1 and X2), satisfaction with life (SWLS), delivery expectation/experience (W-DEQ), and specific fears. Results: Most (90%) of the responders were nulliparous. As many as 75% of the participants reported low to moderate tokophobia, whereas 25% exhibited high or very high fear of childbirth. Pathological fear occurred in 1.6% of the participants. The most significant was the fear of having an episiotomy followed by fear of having no control on the situation and fear of pain. An association exists between a preferred elective cesarean birth and tokophobia. Conclusions: The results draw attention to the need for early detection and treatment of fear of childbirth. The data may help identifying women at risk that require prenatal psychological intervention.

Objective: To investigate the role of adjuvant 17-α-hydroxy-progesterone caproate (17OHP-C) in reducing the risk of preterm delivery <34 weeks and adverse perinatal outcomes in women with ≥3 second trimester pregnancy losses attributed to cervical insufficiency undergoing prophylactic cerclage. Material and methods: Retrospective cohort study of women with prophylactic cerclage placed between 2006 and 2014 divided into a cohort of (i) those receiving adjuvant 17OHP-C (n=43), and (ii) controls with cerclage alone (n=59). Results: Demographic characteristics were comparable in both groups. There was no significant difference in gestational age at delivery between the cerclage-17OHP-C group (33.4±5.6 weeks) and the cerclage-alone group (34.4±4.6 weeks); P=0.33. We noted a non-significant increase for deliveries <34 weeks in the cerclage-17OHP-C group (44.2%) compared to controls (28.8%) which remained non-significant after adjusting for confounders; P=0.46. There was no statistically significant difference in the rate of delivery <37, 32, 28 and 24 weeks. Adverse neonatal outcomes were comparable in both groups (cerclage-17OHP-C 48.8% vs. cerclage-alone 39%); P=0.43. Conclusion: Intramuscular 17OHP-C in combination with prophylactic cerclage in women with cervical insufficiency and ≥3 second trimester pregnancy losses had no synergistic effect in reducing the rate of recurrent preterm birth or improving perinatal outcomes.

Objective: To analyze the accuracy of ultrasound prediction of birth weight discordance (BWD) and the influence of chorionicity and fetal growth restriction (FGR) on ultrasound performance. Methods: Retrospective analysis of 176 twin pregnancies at a Portuguese tertiary center, between 2008 and 2014. Last ultrasound biometry was recorded. Cases with delivery before 24 weeks, fetal malformations, interval between last ultrasound and deliver >3 weeks, twin-to-twin transfusion syndrome and monoamniotic pregnancies were excluded. The accuracy of prediction of BWD was assessed using the area under the receiver-operating characteristics curve (AUC). Results: BWD ≥20% was present in 21.6% of twin pregnancies. EBW had the best predictive performance for BWD (AUC 0.838, 95%CI 0.760–0.916), with a negative predictive value of 86.9% and a positive predictive value of 51.3%. Chorionicity did not influence ultrasound performance. None of the biometric variables analyzed was predictive of BWD in pregnancies without FGR. Conclusion: The accuracy of ultrasound in the prediction of BWD is limited, particularly in pregnancies without fetal growth restriction. Clinical decisions should not rely on BWD alone.

Preeclampsia (PE) affects 2–5% of all pregnancies. It is a multifactorial disease, but it has been estimated that 35% of the variance in liability of PE are attributable to maternal genetic effects and 20% to fetal genetic effects. PE has also been reported in women delivering children with Beckwith-Wiedemann syndrome (BWS, OMIM 130650), a disorder associated with aberrant methylation at genomically imprinted loci. Among others, members of the NLRP gene family are involved in the etiology of imprinting defects. Thus, a functional link between PE, NLRP gene mutations and aberrant imprinting can be assumed. Therefore we analyzed a cohort of 47 PE patients for NLRP gene mutations by next generation sequencing. In 25 fetuses where DNA was available we determined the methylation status at the imprinted locus. With the exception of one woman heterozygous for a missense variant in the NLRP7 gene (NM_001127255.1(NLRP7):c.542G>C) we could not identify further carriers, in the fetal DNA normal methylation patterns were observed. Thus, our negative screening results in a well-defined cohort indicate that NLRP mutations are not a relevant cause of PE, though strong evidence for a functional link between NLRP mutations, PE and aberrant methylation exist.

Aim: Autopsy is a beneficial procedure to determine the cause of death and the frequency of anomalies in perinatal losses. Even in the event of an autopsy not providing any additional information, completion of the procedure confirming the clinical diagnoses gives reassurance to both clinicians and parents. Here we present a 15-year archival study based on findings of perinatal autopsies. Design and methods: Four hundred and eighty-six cases from our archive were reviewed and according to the findings they were divided into three subcategories; (1) miscarriages (MCF); (2) fetuses terminated (FTA) for vital anomalies detected by prenatal ultrasonography; (3) premature or term newborns died within first month of life (neonates: NN). Autopsies were documented and classified according to week/age of cases, anomalies and causes of abortion or death. Results: Two hundred and twenty-six of 486 cases (46.5%) were in MCF group while 227 (46.7%) and 33 (6.8%) were of them in FTA and NN groups, respectively. In FTA group, the most frequent anomaly detected was neural tube defects. In NN group, prematurity related complications were the most common cause of death. The autopsy process was found valuable in 39.7% of all cases. Conclusions: We suggest that autopsy procedure is diagnostically valuable even in situations when there is USG findings that are confirming FTAs or there is no important major fetal or placental anomaly detected in MCFs.

Objective: We performed the present study to investigate the feto-maternal osmotic relationship at term with the hypothesis that, in contrast to the literature, maternal plasma osmolality is lower than fetal levels. In a previous study, we found that maternal plasma sodium at delivery was consistently lower than the sodium in the umbilical artery. Our aim was to corroborate these results with analysis of osmolality. Methods: Blood was sampled from 30 women immediately before cesarean section and from the umbilical artery and vein before cord clamping and osmolality, sodium and albumin were analyzed. Results: Maternal osmolality was (mean; 95% confidence interval) 287.0 (285.8–288.2) mOsmkg/kg, arterial cord osmolality was 289.4 (287.9–291.0) mOsm/kg and venous cord osmolality was 287.3 (286.0–288.5) mOsm/kg. The paired difference between maternal and umbilical arterial osmolality was mean (SD) −2.4 (3.3) mOsm/kg (P<0.001), between maternal and umbilical vein −0.3 (3.0) mOsm/kg (P=0.63) and between umbilical artery and vein −2.1 (2.8) mOsm/kg (P<0.001). Conclusion: Maternal osmolality was significantly lower than arterial cord osmolality confirming our previous results. The feto-maternal osmotic gradient favors water transport from the mother to the fetus and may increase the fetal risk of water intoxication when the mother ingests or is administered large volumes of electrolyte free solutions.

Objectives: To study the normal oxygen saturation trends and fetomaternal correlates in healthy term newborns within 30 min of life born by normal vaginal delivery (NVD) and elective cesarean section (CS). Materials and methods:: A cross-sectional study was conducted on 200 healthy term newborns born by NVD and elective CS at a tertiary care centre. Routine care as per the Neonatal Resuscitation Program (NRP) 2015 (Wyckoff MH, Aziz K, Escobedo MB, Kapadia VS, Kattwinkel J, Perlman JM, et al. Part 13: neonatal resuscitation: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132:S543–60) protocol was given and pre-ductal arterial oxygen saturation was assessed by pulse oximetry at different intervals after birth. Results: The mean peripheral oxygen saturation (SpO 2 ) was 85.4%, 90.8%, 94.1%, 95.7%, 96.7% and 97.4% at 5, 10, 15, 20, 25 and 30 min, respectively, after birth. Higher mean SpO 2 was observed in NVD compared to elective CS (P<0.005). The mean time for SpO 2 to reach >90% was 9.13 min in NVD and 12.31 min in elective CS (P<0.001). Maternal hemoglobin (Hb) (r=−0.15; P<0.01), birth weight (r=−0.125; P<0.05) and Apgar at 10 min (r=0.33; P<0.001) were significantly correlated with SpO 2 of newborns at 10 min of life. Conclusion: Our study defines normal SpO 2 levels in healthy term newborns in the first 30 min of life born by NVD and elective CS. Babies born by NVD had significantly higher SpO 2 levels and attained SpO 2 >90% faster than those born by elective CS. Maternal Hb, birth weight and Apgar at 10 min were significant factors affecting SpO 2 levels of newborns at 10 min of life.

Objective: We examined the causes of death amongst full term stillbirths and early neonatal deaths. Methods: Our cohort includes women in the Region of Southern Denmark, who gave birth at full term to a stillborn infant or a neonate who died within the first 7 days from 2010 through 2014. Demographic, biometric and clinical variables were analyzed to assess the causes of death using two classification systems: causes of death and associated conditions (CODAC) and a Danish system based on initial causes of fetal death (INCODE). Results: A total of 95 maternal-infant cases were included. Using the CODAC and INCODE classification systems, we found that the causes of death were unknown in 59/95 (62.1%). The second most common cause of death in CODAC was congenital anomalies in 10/95 (10.5%), similar to INCODE with fetal, genetic, structural and karyotypic anomalies in 11/95 (11.6%). The majority of the mothers were healthy, primiparous, non-smokers, aged 20–34 years and with a normal body mass index (BMI). Conclusion: Based on an unselected cohort from an entire region in Denmark, the cause of stillbirth and early neonatal deaths among full term infants remained unknown for the vast majority.

Objective: To compare the results of pulse oximetry screening for critical congenital heart disease (CCHD) in newborn infants performed at <24 h and >24 h following. Method: Measurements were taken for each group at <24 h and >24 h following birth. Echocardiography was performed if the SpO2 readings remained abnormal results. Results: A total of 4518 newborns were included in this prospective descriptive study. Of these, 2484 (60.3%) were delivered vaginally and 1685 (39.7%) by cesarean section. Median time points of the screening were 25.4 (25.3–25.5) vs. 17.3 (12.2–22.4) hours after birth. In 4109 infants screened 24 h after birth, the mean pre- and postductal oxygen saturations (SpO2) were 96.5±1.99 and 97.7±1.98, while 127 infants screened within 24 h of mean preductal and postductal SpO2 were 91.33±2.64 and 94.0±4.44. No CCHD was detected during the study period. Pulse oximetry screening was false positive for CCHD in 9 of 4109 infants (0.02%); of these, six infants were referred to pediatric cardiology and three cases were diagnosed as other significant, non-cardiac pathology. There were two cases with AVSD (atrioventricular septal defect, three cases with ventricular septal defect (VSD), and one case with patent ductus arteriosus (PDA). Conclusions: Saturation values are different between <24-h and >24-h neonates in pulse oximetry screening. The screening in this study identified infants with other important pathologies, this forms an added value as an assessment tool for newborn infants.

Background: Lipid peroxidation mediated by reactive oxygen species is a major contributor to oxidative stress. Docosahexaenoic acid (DHA) has anti-oxidant and neuroprotective properties. Our objective was to assess how oxidative stress measured by lipid peroxidation was modified by DHA in a newborn piglet model of hypoxia-ischemia (HI). Methods: Fifty-five piglets were randomized to (i) hypoxia, (ii) DHA, (iii) hypothermia, (iv) hypothermia+DHA or (v) sham. All groups but sham were subjected to hypoxia by breathing 8% O 2 . DHA was administered 210 min after end of hypoxia and the piglets were euthanized 9.5 h after end of hypoxia. Urine and blood were harvested at these two time points and analyzed for F 4 -neuroprostanes, F 2 -isoprostanes, neurofuranes and isofuranes using UPLC-MS/MS. Results: F 4 -neuroprostanes in urine were significantly reduced (P=0.006) in groups receiving DHA. Hypoxia (median, IQR 1652 nM, 610–4557) vs. DHA (440 nM, 367–738, P=0.016) and hypothermia (median, IQR 1338 nM, 744–3085) vs. hypothermia+DHA (356 nM, 264–1180, P=0.006). The isoprostane compound 8-iso-PGF2α was significantly lower (P=0.011) in the DHA group compared to the hypoxia group. No significant differences were found between the groups in blood. Conclusion: DHA significantly reduces oxidative stress by measures of lipid peroxidation following HI in both normothermic and hypothermic piglets.

Objective: To investigate whether fetal pulmonary artery acceleration to ejection time (PATET) ratio can predict or rule out subsequent diagnosis of transient tachypnea of the newborn (TTN). Methods: This prospective cohort study included 105 pregnant women in labor, who met the inclusion criteria. Eighteen of these women were removed from the study cohort, because of an inability to acquire sufficient Doppler waveforms and a longer duration of deliveries. According to subsequent diagnosis of TTN in the neonate, the two groups were constituted, TTN+ and TTN−. Results: There were no statistically significant differences between the groups regarding maternal obstetric and demographic features. The neonatal intensive care unit (NICU) submission rate was significantly higher in the TTN+ group (100%, 17%, P<0.0001, respectively). Regarding the fetal pulmonary artery Doppler findings, PATET ratio in the TTN+ group was significantly lower than the TTN− group (0.307 vs. 0.389, P<0.0001, respectively). The PATET ratio and diagnosis of TTN were inversely correlated (r=−0.41, P<0.001), even if adjusted for birth weight, gestational age and fetal gender (r=0.42, P=0.0021). The cut-off value of 0.319 provided 82.7% specificity, 83.3% sensitivity, 96% negative predictive value and 41.6% positive predictive value. Additionally intraobserver ICC for PATET was found to be 0.86. Conclusion: The fetal PATET ratio seems to serve as a promising tool to rule out subsequent diagnosis of TTN.