Volume 47, Issue 1

Background The ductus venosus agenesis (DVA) is a rare condition with a variable prognosis that relies partly on the presence of associated conditions. The purpose of our study was to analyze the literature regarding the post-natal outcome of fetuses with DVA associated with fetal malformations, in order to discuss the best management options for couples. Methods We performed a systematic review of the literature of MEDLINE and SCOPUS electronic databases in a 25-year period from 1992 to September 2017. Methods We found 340 cases of DVA associated with fetal abnormalities. The most common chromosomal abnormalities were: monosomy X (12/48, 25%), trisomy 21 (11/48, 22.9%) and trisomy 18 (6/48, 12.5%). From the 340 cases with DVA, in 31 cases the umbilical venous shunt type was not reported. Of the fetuses, 60.8% (188/309) had an extrahepatic umbilical venous drainage while 39.2% (121/309) presented an intrahepatic connection. The DVA was associated in 71 cases (23.0%) with cardiac abnormalities, in 82 cases (26.5%) with extracardiac abnormalities and in 85 cases (27.5%) with both cardiac and extracardiac abnormalities. Conclusion DVA associated with both cardiac and extracardiac malformations may confer a poorer fetal outcome, a clinically relevant fact that should clarify what can be expected from this entity and help prenatal counseling.

The number of pregnant women with abnormally invasive placenta (AIP) including clinical relevant placenta increta and percreta has markedly increased with a reported incidence of as high as one in 731, By 2020 in the United States, there will be an estimated 4504 new cases of AIP and 130 AIP-associated maternal deaths annually. The preoperative diagnosis and operative management of AIP is challenging. In a planned cesarean delivery, a vertical lower abdominal skin incision is widely used in order to have enough space to perform a hysterotomy above the cranial edge of the placenta to avoid significant fetal and/or maternal hemorrhage. We have used preoperative drainage of the amniotic fluid after epidural anesthesia and immediately before a planned cesarean delivery through a transverse skin incision in five patients with AIP of the anterior uterine wall. With less uterine volume, exteriorization of the gravid uterus is easily performed through a transverse laparotomy. The combination of amnion drainage, transverse laparotomy and exteriorization of the gravid uterus facilitates identification of the exact site of placental implantation, provides adequate space for performing fundal or high anterior or even posterior uterine wall incisions and to deliver the fetus safely while minimizing the risk of placental separation and subsequent uncontrolled blood loss. Furthermore, this technique provides the chance to leave the untouched placenta in situ or to remove the placenta in toto with a uterine wall segment.

Hospital births, when compared to out-of-hospital births, have generally led to not only a significantly reduced maternal and perinatal mortality and morbidity but also an increase in certain interventions. A trend seems to be emerging, especially in the US where some women are requesting home births, which creates ethical challenges for obstetricians and the health care organizations and policy makers. In the developing world, a completely different reality exists. Home births constitute the majority of deliveries in the developing world. There are severe limitations in terms of facilities, health personnel and deeply entrenched cultural and socio-economic conditions militating against hospital births. As a consequence, maternal and perinatal mortality and morbidity remain the highest, especially in Sub-Saharan Africa (SSA). Midwife-assisted planned home birth therefore has a major role to play in increasing the safety of childbirth in SSA. The objective of this paper is to propose a model that can be used to improve the safety of childbirth in low resource countries and to outline why midwife assisted planned home birth with coordination of hospitals is the preferred alternative to unassisted or inadequately assisted planned home birth in SSA.

Background Anthropometric parameters such as birth weight (BW) and adult body height vary between ethnic groups. Ethnic-specific percentile charts are currently being used for the assessment of newborns. However, due to globalization and interethnic families, it is unclear which charts should be used. A correlation between a mother’s height and her child’s BW (1 cm accounts for a 17 g increase in BW) has been observed. The study aims to test differences in small for gestational age (SGA) and large for gestational age (LGA) rates, employing BW percentile charts based on maternal height between ethnic groups. Methods This retrospective study of 2.3 million mother/newborn pairs analyzed BW, gestational age, sex, maternal height and ethnicity from the German perinatal survey (1995–2000). These data were stratified for maternal height (≤157, 158–163, 164–169, 170–175, ≥176 cm) and region of origin (Germany, Central and Northern Europe, North America, Mediterranean region, Eastern Europe, Middle East and North Africa, and Asia excluding Middle East). Percentile charts were calculated for each maternal height group. Results The average BW and maternal height differ significantly between ethnic groups. On current percentile charts, newborns of taller mothers (≥176 cm) have a low rate of SGA and a high rate of LGA, whereas newborns of shorter mothers (≤157 cm) have a high rate of SGA and a low rate of LGA. When the BW data are stratified based on the maternal height, mothers of similar height from different ethnic groups show similar average BWs, SGA and LGA rates. Conclusion Maternal body height has a greater influence on BW than maternal ethnicity. The use of BW percentile charts for maternal height should be considered.

Objective To examine the risk for abnormal chromosomal microarray analysis (CMA) results among fetuses with an apparently isolated pelvic kidney. Methods Data from all CMA analyses performed due to an isolated pelvic kidney reported to the Israeli Ministry of Health between January 2013 and September 2016 were retrospectively obtained. Risk estimation was performed comparing the rate of abnormal observed CMA findings to the general population risk, based on a systematic review encompassing 9272 cases and on local data of 5541 cases. Results Of 120 pregnancies with an isolated pelvic kidney, two gain-of-copy number variants suggesting microduplication syndromes were demonstrated (1.67%). In addition, three variants of unknown significance were detected (2.5%). Conclusion The risk for clinically significant CMA findings among pregnancies with an isolated single pelvic kidney was not significantly different compared to both control populations. The results of our study question the practice of routine CMA analysis in fetuses with an isolated pelvic kidney.

Background To establish gestational specific cutoffs for the soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio as a diagnostic tool for pre-eclampsia (PE) in an Asian population. Methods 82 subjects (48 PE patients and 34 controls) were recruited. sFlt-1 and PlGF were analysed on the Roche Cobas e411 analyzer and their ratio was calculated. Diagnostic performance was evaluated using receiver-operating characteristics (ROC) curves. Optimal cutoffs for sFlt-1/PlGF ratio were determined for different gestation phases. Results The most optimal cut-off for the study group is 32 with a sensitivity and specificity of 85.1% and 100% and Youden Index (J) of 0.85. Applying this cutoff for early-onset PE (EO-PE), sensitivity increased to 95.8% while specificity remains at 100% (J=0.96). However, for late onset PE (LO-PE), sensitivity decreases to 73.9% while specificity remains at 100% (J=0.74). Two cutoffs were further determined for EO-PE and LO-PE – the first focusing on high sensitivity; the second focusing on high specificity. For EO-PE, cutoff <17 yielded sensitivity of 100% and specificity of 94.4% (J=0.94) while cutoff ≥32 yielded sensitivity of 95.8% and specificity of 100% (J=0.95). For LO-PE, cutoff <22 has a sensitivity of 82.6% and a specificity of 91.7% (J=0.74) while cutoff ≥32 yielded sensitivity of 73.9% and specificity of 100% (J=0.74). Conclusion While our study found an overall cutoff at 32 regardless of gestation age, it has limited diagnostic accuracy for LO-PE in our study. Multiple cutoffs focusing on either high sensitivity or high specificity enhance the performance of the sFlt-1/PlGF ratio as a diagnostic tool for PE and contribute to the identification of women at risk of PE in our Asian region.

Background Pregnancy loss is probably the most common problem faced by women worldwide. There are differences in the rates of early and late pregnancy loss based on geography among the developing compared with the developed nations of the world. Most physicians worldwide have different criteria for treating pregnancy loss. Although pregnancy loss is not a disease, it might be best approached with a medical evaluation in order to define the cause and offer specific treatment. Methods This report describes the results obtained by a multi-disciplinary pregnancy loss prevention center in the initial 104 patients. Results The most common diagnoses were Asherman syndrome (intrauterine adhesions), cervical insufficiency and uterine fibroids, accounting for 47% of the patients. When the diagnosis was not obtained, which occurred in 19% of the patients, in vitro fertilization (IVF) was the treatment provided. Specifically diagnosed and treated patients achieved a 91% success rate. The 19 patients without a specific diagnosis who were treated with IVF had a 60% success rate. Thus patients for whom it was possible to specifically diagnose and treat had better results (P<0.01 t -test). There was an overall success rate of 87% including patients lost to follow-up with this multidisciplinary medical approach. Conclusion A pregnancy loss prevention center using the described multidisciplinary model can accomplish success rates of 85–90%. Preventing recurrent pregnancy loss we suggest can best be achieved by a dedicated center with a multidisciplinary medical approach.

Objective Morbidly adherent placenta (MAP) is a clinical condition the prevalance of which is steadily increasing. It is described as the invasion of the placenta into the uterine wall through the myometrium and beyond. Several studies have shown that intercellular adhesion molecule-1 (ICAM-1) increases the invasion capability of tumor cells and placental cells. In our study, we investigated the expression of ICAM-1 in MAP cases. Methods This is a prospective case-control study. Eighty-nine patients who were diagnosed with MAP and 96 patients, without adherent placenta, as a control group were included in the study. ICAM-1 staining was examined by immuno-histochemical staining in placental samples. Results Of the 89 patients in the MAP group, 72 (80.8%) showed positive staining, while 26 (27%) did so in the control group. ICAM-1 positive staining in the MAP group was statistically significantly higher (P=0.03). Conclusion This is the first study investigating the relationship between MAP and ICAM-1 in the literature. In our study, we showed that ICAM-1 expression increased in the MAP group.

Objective To investigate the variability in the prevalences of selected birth risks in women of different heights and weights. Methods Data from the German Perinatal Survey of 1998–2000 were analyzed: 503,468 cases contributed to our analysis of the prevalences of selected birth risks specified according to maternal weight groups, 502,562 cases contributed to our analysis according to maternal height groups and 43,928 cases contributed to our analysis of birth risks in women with a body mass index (BMI) of 21–23 kg/m 2 but different heights and weights. Data analysis was performed using SPSS version 22. Results Some birth risks varied substantially by maternal height in women with a “normal” BMI of 21–23 kg/m 2 : the prevalence of post-term birth increased from 8.7% in women with a height of 150 cm to 13.5% in 185 cm tall women, the prevalence of preterm birth decreased from 5.9% (150 cm tall women) to 3.1% (185 cm tall women), a pathologic cardiotocography (CTG) or poor fetal heart sounds on auscultation occurred in 19.4% of the 150 cm tall women but only in 9.2% of 185 cm tall women and cephalopelvic disproportion decreased from 12.3% (150 cm tall women) to 1.2% (185 cm tall women). Analyses of women in different body height and weight groups (without restriction of BMI) likewise showed differences in the prevalences of some birth risks. Conclusion Birth risks may vary by height and weight in women with the same, “normal” BMI. BMI should not be the only way by which the impact of maternal height and weight is assessed with regard to perinatal outcomes such as birth risks.

Fetomaternal hemorrhage (FMH) is an obstetrical challenge. It is defined as a passage of fetal blood into the maternal circulation or vice versa , which might complicate pregnancy or delivery. Most cases of acute and chronic FMH are idiopathic in origin and involve uncomplicated near-term pregnancies. Yet, due to the lack of universal screening, heterogeneous clinical presentation and insufficient clinicians awareness, in some cases FMH may present as immediate fetal compromise or even stillbirth as the most devastating consequence. We made a review of the literature of the FMH clinical cases of fetal/neonatal death in order to focus on the available diagnostic tools and their limitations. Cardiotocography, biophysical profile, middle cerebral artery peak systolic volume and current laboratory tests were studied and evaluated as diagnostic tools for FMH. International guidelines are needed to help clinicians make a prompt identification of FMH. Moreover, a standardized management protocol is essential in order to improve fetal-neonatal outcomes.

Background The purpose of our study was to quantify the fetal myocardial function in pregnant women with diabetic diseases (FDM) and in normal controls (FC) using speckle tracking echocardiography (STE). Methods In this prospective study, the myocardial strain and dyssynchrony were analyzed using STE in a transversal four-chamber view in 180 fetuses (53 FDM, 127 FC) between 19 and 39 weeks of gestation. The measurements of the global and segmental longitudinal strain of both chambers (2C) and of the single left chamber (1C) were executed offline via QLab 10.5 (Philips Medical Systems, Andover, MA, USA). We assessed dyssynchrony as the time difference between peaks in strain in the mid segments of both chambers (interventricular dyssynchrony, 2C_DYS) and of the single left chamber (intraventricular dyssynchrony, 1C_DYS). Results Measurements were feasible with a high median frame rate of 199 frames/s (1 st quartile: 174, 3 rd quartile: 199). The global and segmental myocardial longitudinal strain of 2C and 1C were decreased and 2C_DYS and 1C_DYS were increased in pregnancies with diabetes compared to normal controls. Conclusion Our study demonstrates that fetal hearts affected by maternal diabetes mellitus (DM) show low myocardial strain values and high interventricular dyssynchrony. Two-chamber interventricular dyssynchrony has the potential to become a diagnostic marker for DM.

Objective To assess the usefulness of the antenatal fetal neurodevelopmental test for the prediction of postnatal developmental disabilities. Methods Fetal behavior was assessed with Kurjak’s antenatal neurodevelopmental test (KANET) using four-dimensional ultrasound between 28 and 38 weeks of gestation. A score range of 0–5 was characterized as abnormal, from 6 to 9 was considered borderline, and 10–16 was normal. After birth, follow-up was conducted for at least 2 years in all fetuses. Results There were 337 normal (95.47%) and 16 borderline (4.53%) cases among the 353 cases studied, whereas there was no abnormal case. Five cases with postnatal developmental disabilities (one case of Werdig-Hoffmann disease diagnosed just after delivery, one case of autism spectrum disorder diagnosed at 24 months, one case of Ullrich congenital muscular dystrophy diagnosed at 9 months and two cases of developmental disorders diagnosed at age 3 and 18 months) were noted among the 337 normal cases (1.48%), whereas three cases with developmental disabilities (one case of motor development delay diagnosed at 6 months, one case of Duchenne muscular dystrophy diagnosed at 18 months and one case of autism spectrum disorder diagnosed at age 30 months) were found among the 16 borderline cases (18.75%). There was a significant difference in the prevalence of postnatal developmental disabilities between the normal and borderline KANET groups (P<0.001). Conclusion Our results suggest that the KANET assessment may be a useful diagnostic modality for the prediction of postnatal developmental disabilities.

Background Oxidative stress plays an important part in the pathophysiology of hypoxic-ischemic encephalopathy (HIE) and is reliably measured through prostanoids following lipid peroxidation of polyunsaturated fatty acids (PUFAs). The aim of the study is to measure oxidative stress in the prefrontal cortex, white matter and hippocampus in the brains of hypoxic-ischemic piglets treated with docosahexaenoic acid (DHA) and therapeutic hypothermia (TH) and investigate the additive effects of DHA on hypothermia by factorial design. Methods Fifty-five piglets were randomized as having severe global hypoxia (n=48) or not (sham, n=7). Hypoxic piglets were further randomized: vehicle (VEH), DHA, VEH+hypothermia (HT) or HT+DHA. A total of 5 mg/kg DHA was given intravenously 210 min after the end of hypoxia. Brain tissues were analyzed using liquid chromatography triple quadrupole mass spectrometry technique (LC-MS). A two-way analysis of variance (ANOVA) was performed with DHA and HT as main effects. Results In the white matter, we found main effects of DHA on DH-isoprostanes (P=0.030) and a main effect of HT on F 4 -neuroprostanes (F 4 -NeuroPs) (P=0.007), F 2 -isoprostanes (F 2 -IsoPs) (P=0.043) and DH-isoprostanes (P=0.023). In the cortex, the ANOVA analysis showed the interactions of main effects between DHA and HT for neurofuranes (NeuroFs) (P=0.092) and DH-isoprostanes (P=0.015) as DHA significantly reduced lipid peroxidation in the absence of HT. DHA compared to VEH significantly reduced NeuroFs (P=0.019) and DH-isoprostanes (P=0.010). No differences were found in the hippocampus. Conclusion After severe hypoxia, HT reduced lipid peroxidation in the white matter but not in the cortical gray matter. HT attenuated the reducing effect of DHA on lipid peroxidation in the cortex. Further studies are needed to determine whether DHA can be an effective add-on therapy for TH.

Objective To determine the frequency of detection of cytomegalovirus (CMV) among infants evaluated for late-onset sepsis in the neonatal intensive care unit (NICU). Methods This study was a prospective cohort study. Results During the 13-month study, 84 infants underwent 116 sepsis evaluations, and CMV DNA was detected in saliva in three (4%) infants (median: gestational age 28 weeks, birth weight 950 g), representing 5% (n=6) of all sepsis evaluations. One infant had CMV DNA detected in saliva in all four sepsis evaluations. Two infants had acquired CMV infection, while the timing of CMV acquisition could not be determined in one infant. Two of the three infants had concomitant Gram-negative bacteremia and urinary tract infections (UTIs), two developed severe bronchopulmonary dysplasia (BPD) and none died. Conclusion Detection of CMV DNA in saliva occurred in 4% of infants and 5% of sepsis evaluations. Persistence of CMV DNA shedding in saliva made attribution of clinical illness difficult to ascertain.

Objective To explore whether the average price of houses per postcode sector [sector house average prices (SHAP)] is related to perinatal outcomes and whether gestational age would be lower and mortality higher in the least expensive areas compared to the most expensive. Methods All neonatal unit admissions at King’s College Hospital from 1/1/2012 to 31/12/2016 were reviewed. The SHAP was retrieved from the Land Registry and the population was divided in equal quintiles with quintiles 1 and 5 representing the most and least expensive areas, respectively. Gestational age and birth weight z-score were collected. Mortality was defined as death before discharge from neonatal care. Results Three thousand three hundred and sixty infants were included and divided in quintiles consisting of 672 infants. Gestational age was lower in quintile 5 compared to all other quintiles (adjusted P<0.001). Birthweight z-score was not significantly different between the quintiles. The SHAP was lower in the infants who died before discharge (n=92) compared to the SHAP of the infants who were alive at discharge (n=3268) (P<0.001). Infants of quintile 5 had 6 times higher risk of death before discharge from neonatal care compared to infants of quintile 1. Conclusion Low SHAPs were associated with poorer perinatal outcomes suggesting SHAP could potentially be used in perinatal populations to determine socio-economic status and associated outcomes.

Background Mothers of preterm (PT) infants have difficulty providing adequate quantities of human milk (HM) for their babies during their hospital stay. The macronutrient content in HM changes over time, varying across and within individual mothers. The research aim of the strudy was to describe the intake of mothers’ own milk (MOM) and its composition according to gestational (GA) and postnatal age (PNA) in infants born <32 weeks’ GA and to correlate them with neonatal weight, length and morbidities. Methods A prospective observational study of 176 premature infants in a unit without a donor milk bank was conducted. Daily milk intake was recorded. HM macronutrients were determined by mid-infrared spectrophotometric analysis at 7, 15 and 30 days after delivery and monthly until hospital discharge. Results Intake of MOM increased during the first 2 weeks after birth and decreased steadily thereafter. Protein concentration varied inversely with PNA. Carbohydrate and lipid concentrations increased over the first few days and remained stable thereafter. A fall in weight percentiles from birth to 60 days was found. No correlation was found between total protein and calorie intakes at 3 and 15 days of life and growth velocity (GV) between 15 and 30 days, even when broken down into parenteral nutrition (PN), formula and MOM. Conclusion To improve MOM feeding in PT newborns, intensive support strategies at the prenatal stage along entire hospitalization income should be encouraged. New protocols for fortification of HM should be implemented to optimize postnatal weight gain while preserving the health benefits of HM.

Background 8-Oxoguanine DNA-glycosylase 1 (OGG1) and mutY DNA glycosylase (MUTYH) are crucial in the repair of the oxidative DNA lesion 7,8-dihydro-8-oxoguanine caused by hypoxia-reoxygenation injury. Our objective was to compare the gene expression changes after hypoxia-reoxygenation in neonatal Ogg1 - Mutyh double knockout mice (OM) and wildtype mice (WT), and study the gene response in OM after hyperoxic reoxygenation compared to normoxic. Methods Postnatal day 7 mice were subjected to 2 h of hypoxia (8% O 2 ) followed by reoxygenation in either 60% O 2 or air, and sacrificed right after completed reoxygenation (T0h) or after 72 h (T72h). The gene expression of 44 a priori selected genes was examined in the hippocampus/striatum and lung. Results We found that OM had an altered gene response compared to WT in 21 genes in the brain and 24 genes in the lung. OM had a lower expression than WT of inflammatory genes in the brain at T0h, and higher expression at T72h in both the brain and lung. In the lung of OM, five genes were differentially expressed after hyperoxic reoxygenation compared to normoxic. Conclusion For the first time, we report that Ogg1 and Mutyh in combination protect against late inflammatory gene activation in the hippocampus/striatum and lung after neonatal hypoxia-reoxygenation.

Background The infant mortality rate (IMR), a key indicator of the quality of a healthcare system, has remained at approximately 3.5‰ for the past 10 years in Germany. Generic quality indicators (QIs), as used in Germany since 2010, greatly help in ensuring such a good value but do not seem to be able to further reduce the IMR. The neonatal mortality rate (NMR) contributes to 65–70% of the IMR. We therefore propose single-case analysis of neonatal deaths as an additional method and show an efficient way to implement this approach. Methods We used the Nordic-Baltic classification (NBC) to detect avoidable neonatal deaths. We applied this classification to a sample of 1968 neonatal death records, which represent over 90% of all neonatal deaths in East Berlin from 1973 to 1989. All cases were analyzed as to their preventability based on the complete perinatal and clinical data by a special commission of different experts. The NBC was automatically applied through natural language processing and an ontology-based terminology server. Results The NBC was used to select the group of cases that had a high potential of avoidance. The selected group represented 6.0% of all cases, and 60.4% of the cases within that group were judged avoidable or conditionally avoidable. The automatic detection of malformations showed an F1 score of 0.94. Conclusion The results show that our method can be applied automatically and is a powerful and highly specific tool for selecting potentially avoidable neonatal deaths and thus for supporting efficient single-case analysis.

Background In this pilot study, the effects of selective serotonin reuptake inhibitors (SSRIs) and psychological intervention on fetal growth characteristics and neonatal outcomes were evaluated in two different groups of women affected by prenatal depression. Methods Forty-seven pregnant women diagnosed with major depression were divided into two different treatment groups according to the severity of their depression. The first group was treated with a combination of pharmacotherapy and psychological support. The second group (milder depression) was treated with psychological support only. The control group (CG) was made up of 26 healthy pregnant women. All of the patients and controls were assessed by means of a structured clinical interview and different self-reported questionnaires. Fetal ultrasonography assessments were performed in the second and third trimesters. Neonatal outcomes were evaluated at delivery. Results The infants of both treatment groups showed significant alterations in fetal biometry and a higher rate of low birth weight (LBW) with respect to controls. The infants of the patients treated with psychological support showed only a significantly higher rate of head circumference, <10 th percentile with respect to controls. No significant difference was found between the two patient groups when fetal growth characteristics and neonatal outcomes were taken into account. Conclusion The data obtained from this study shed light on the effects of pharmacological and psychological treatment of prenatal depression on fetal growth.