Volume 51, Issue 9

Background Dexamethasone administration can reduce bronchopulmonary dysplasia, our objective was to identify long term adverse effects. Content A systematic review was performed to determine the childhood and adolescent cardiopulmonary and cognitive effects of dexamethasone systemically administered to preterm infants during neonatal intensive care. Relevant studies were identified by searching two electronic health databases and the grey literature. Spirometry assessments were used as respiratory outcomes, blood pressure and echocardiography assessments as cardiovascular outcomes and cognitive and motor function as cognitive outcomes. From 1,479 articles initially identified, 18 studies (overall 1,609 patients) were included (respiratory n=8, cardiovascular n=2, cognitive n=10); all were observational cohort studies. Dexamethasone exposure was associated with worse pulmonary outcomes in children and adolescents (more abnormal FVC and FEV1:FVC z scores). Dexamethasone exposure was associated in one study with lower IQ scores compared to preterm controls (mean 78.2 [SD 15.0] vs. 84.4 [12.6], [p=0.008]) and in two others was associated with lower total and performance IQ when compared to term controls (p<0.001). Summary and outlook Postnatal dexamethasone exposure has a negative influence on pulmonary and cognitive outcomes in childhood and adolescence. Medications with a better benefit to risk profile need to be identified.

Background Shoulder dystocia is a peracute mechanical dystocia and a prepartum, usually unpredictable, life-threatening entity with significant forensic implications due to significantly poor perinatal outcome, especially permanent disability or perinatal death. Content To better objectify the graduation and to include other important clinical parameters, we believe it is appropriate to present a proposal for a complete perinatal weighted graduation of shoulder dystocia, based on several years of numerous other and our own clinical and forensic studies and thematic biobibliography. Obstetric maneuvers, neonatal outcome, and maternal outcome are three components, which are evaluated according to the severity of 0–4 proposed components. Thus, the gradation is ultimately in four degrees according to the total score: I. degreee, score 0–3: slightly shoulder dystocia with simple obstetric interventions, but without birth injuries; II. degree, score 4–7: mild shoulder dystocia resolved by external, secondary interventions and minor injuries; III. degree, score 8–10: severe shoulder dystocia with severe peripartum injuries; IV. degree, score 11–12: extremely difficult, severe shoulder dystocia with ultima ratio interventions applied and resulting extremely severe injuries with chronic disability, including perinatal death. Summary As a clinically evaluated graduation, it certainly has an applicable long-term anamnestic and prognostic component for subsequent pregnancies and access to subsequent births, as it includes all relevant components of clinical forensic objectification.

Objectives To investigate the incidence and risk factors of bilobate placenta, as well as to assess its impact on preeclampsia (PE), preterm delivery (PTD) and small-for-gestational age (SGA) neonates. Methods A prospective study of singleton pregnancies, undergoing routine anomaly scan at 20 +0 –23 +6 gestational weeks, was conducted, between 2018 and 2022. The impact of prenatally diagnosed bilobate placenta on PE, PTD and SGA was assessed. Multivariate logistic regression models were employed to assess the independent association between bilobate placenta and the main pregnancy outcomes, using specific confounders. Additionally, a risk factor analysis was performed. Results The study population included 6,454 pregnancies; the incidence of prenatally diagnosed bilobate placenta was 2.0 % (n=129). Bilobate placenta was associated with PE (aOR: 1.721; 95 % CI: 1.014–2.922), while no statistically significant association was found between this anatomical variation and SGA (aOR: 1.059; 95 % CI: 0.665–1.686) or PTD (aOR: 1.317; 95 % CI: 0.773–2.246). Furthermore, pregnancies with prenatally diagnosed bilobate placenta had an increased prevalence of abnormal cord insertion (marginal or velamentous) (9.8 vs. 27.1 %; p<0.001) and increased mean UtA PI z-score (0.03 vs. 0.23; p=0.039). Conception via ART (aOR: 3.669; 95 % CI: 2.248–5.989), previous history of 1st trimester miscarriage (aOR: 1.814; 95 % CI: 1.218–2.700) and advancing maternal age (aOR: 1.069; 95 % CI: 1.031–1.110) were identified as major risk factors for bilobate placenta. Conclusions Bilobate placenta, excluding cases of co-existing vasa previa, is associated with higher incidence of PE, increased mean UtA PI z-score and higher probability of abnormal cord insertion, but not with increased risk for SGA or PTD. It is more common in pregnancies following ART and in women with a previous 1st trimester miscarriage.

Objectives To investigate whether high mobility group box 1 (HMGB1) is involved in unexplained recurrent pregnancy loss (uRPL). Methods Plasma levels of HMGB1 were measured by ELISA in non-pregnant women with (n=44) and without (n=53 controls) uRPL. Their platelets and plasma-derived microvesicles (MVs) were also assayed for HMGB1. Endometrial biopsies were taken in selected uRPL (n=5) and control women (n=5) and the tissue expression of HMGB1 was determined by western blot and immunohistochemistry (IHC). Results plasma levels of HMGB1 were significantly higher in women with uRPL than in control women. HMGB1 content in platelets and MVs obtained from women with uRPL was significantly higher than that obtained from control women. HMGB1 expression in endometrium was higher in tissues obtained from women with uRPL than in tissues obtained from control women. IHC analysis revealed that HMGB1 is expressed in endometrium with different patterns between uRPL and control women. Conclusions HMGB1 could be involved in uRPL.

Objectives Two major complications of monochorionic diamniotic (MCDA) twin pregnancies are twin to twin transfusion syndrome (TTTS) and birthweight discordance. The current screening ultrasound test for these pathologies combines the detection of nuchal translucency discrepancy and abnormal ductus venosus in at least one twin, in the first trimester. We aim to determine whether combining the presence of velamentous cord insertion in at least one twin increases screening efficiency. Methods This was a retrospective cohort with a sample of 136 MCDA twin pregnancies followed at Centro Hospitalar Universitário São João, during a 16-year period. Results The combination of abnormal ductus venosus in at least one twin and nuchal translucency discrepancy is associated with the development of TTTS with an OR of 10.455, but not with birthweight discordance. The combination of these first trimester markers with velamentous cord insertion is not associated with the development of either outcome. Conclusions The presence of velamentous cord insertion in MCDA pregnancies is not associated to TTTS development. Therefore, the addition of this marker to the first trimester screening would not effectively predict the development of birthweight discordance or TTTS. However, a positive currently used screening test increases the risk of developing TTTS by about ten times.

Objectives Gestational diabetes (GDM) is a common complication during pregnancy that is strongly associated with adverse fetal and maternal outcomes. Advanced maternal age (≥35 years) is a known risk factor for GDM. Studies advocate that GDM comprises distinctive metabolic entities, suggesting an individualized approach based on early pregnancy characteristics (such as 75 g oGTT values, maternal age, obstetric history). Methods The oGTT blood glucose levels of 1,664 women were categorized into isolated fasting hyperglycemia (GDM-IFH), isolated postprandial hyperglycemia (GDM-IPH) and combined hyperglycemia (GDM-CH), using the levels of the fasting, 1 h and 2 h values after glucose application. These three subtypes were analysed regarding baseline characteristics as well as fetal and maternal outcome in the context of maternal age. Results This analysis reveals that the 75 g oGTT levels and maternal age can distinguish metabolic phenotypes in women with GDM. The overall rate of insulin therapy required was higher in women from the GDM-CH group and increased with maternal age (31.7 %, 38.2 %, <35 years, ≥35–39 years respectively, vs. total insulin rate 22.3 %, p-value <0.001). Women ≥35 years displayed a significantly higher caesarean delivery (CD) rate (<35 years 34.6 %, 38.4 %, 41.1 % vs. ≥35 years 54.8 %, 47.6 %, 46.5 %, GDM-IFH, GDM-IPH, GDM-CH respectively, p-value <0.001). Conclusions Women with fasting hyperglycemia, especially those with combined hyperglycemia and advanced maternal age (AMA) display a higher risk for unfavorable perinatal outcome. A categorization based on oGTT values and maternal age, as well as other characteristics can facilitate a basis for clinical risk stratification. Women at risk should receive an individualized and intensified perinatal care as well as interventional therapies.

Objectives Asthma is a common chronic and burdensome disease which typically begins in childhood. The aim of this study was to assess perinatal and obstetric factors which may increase the risk of developing asthma in the offspring. Methods Data from five consecutive waves (n=7,073 children, from birth to 15 years old) from a nationally-representative birth cohort of people born in the United Kingdom between 2000 and 2002, the Millennium Cohort Study (MCS), were used. The Kaplan–Meier survival curve was used to graphically display the risk of developing asthma from early childhood to adolescence. The Z-based Wald test was used to prove significant covariate loading. Results Cox regression analyzing the influence of covariates on asthma development risk showed a significant likelihood ratio test, χ 2 (18)=899.30, p<0.01. A parent with asthma (OR=2.02, p<0.01), a younger maternal age at delivery (OR=0.98, p<0.05), and the use of assisted reproductive technology (OR=1.43, p<0.05) were associated with an increased risk of developing asthma in the offspring. Conclusions Perinatal factors (a younger maternal age, assisted reproductive technology) and a parental factor (a parent with asthma) increased the risk for developing asthma in the offspring.

Objectives To explore the association between COVID-19 severity and pregnancy using measures such as COVID-19 ordinal scale severity score, hospitalization, intensive care unit (ICU) admission, oxygen supplementation, invasive mechanical ventilation, and death. Methods We conducted a retrospective, multicenter cohort study to understand the association between COVID-19 severity and pregnancy. We reviewed consecutive charts of adult females, ages 18–45, with laboratory testing for SARS-CoV-2 infection between March 1, 2020, and August 31, 2020. Cases were patients diagnosed with COVID-19 during pregnancy, whereas controls were not pregnant at the time of COVID-19 diagnosis. Primary endpoints were the COVID-19 severity score at presentation (within four hours) and the nadir of the clinical course. The secondary endpoints were the proportion of patients requiring hospitalization, ICU admission, oxygen supplementation, invasive mechanical ventilation, and death. Results A higher proportion of pregnant women had moderate to severe COVID-19 disease at the nadir of the clinical course than non-pregnant women (25 vs. 16.1 %, p=0.04, respectively). There was a higher rate of hospitalization (25.6 vs. 17.2 %), ICU admission (8.9 vs. 4.4 %), need for vasoactive substances (5.0 vs. 2.8 %), and invasive mechanical ventilation (5.6 vs. 2.8 %) in the pregnant cohort. These differences were not significant after applying propensity score matching.We found a high rate of pregnancy complications in our population (40.7 %). The most worrisome is the rate of hypertensive disorders of pregnancy (20.1 %). Conclusions In our propensity score-matched study, COVID-19 in pregnancy is associated with an increased risk of disease severity and pregnancy complications.

Objectives To compare the clinical and morphological characteristics of the “mother-placenta-fetus” system in high risk pregnant women of three groups: no SARS-CoV-2 infection, mild SARS-CoV-2 infection, and severe SARS-CoV-2 infection. Methods A case-control study was performed for all deliveries, at 28 weeks’ gestation or greater, who had standard indications for placental pathologic examination. Three groups were formed: (1) control group (no SARS-CoV-2 infection), (2) mild SARS-CoV-2 infection, (3) severe SARS-CoV-2 infection. High-risk pregnancies were registered in all cases in the study groups. The examination of the placenta and the selection of fragments of placental tissue were carried out in accordance with the consensus recommendations of the Amsterdam Placental Workshop Group. The sections were subjected to standard processing and stained with hematoxylin and eosin according to the standard protocol. All cases were reviewed by two pathologists, which did not know any information on pregnancy outcome and clinical data. Statistical analysis was performed using SPSS, p<0.05 was considered statistically significant. Results Women with severe SARS-CoV-2 infection had an increased rate of multimorbidity including diabetes, chronic hypertension and obesity (p<0.01) compared with the other groups. Placentas at severe COVID-19 course were damaged by both chronic and acute injuries, in comparison to the mild and control groups (p<0.001). Also an important finding in severe COVID-19 was diffuse necrosis of the villous trophoblast – homogenization, diffuse circular eosinophilic masses surrounding the chorionic villi. Conclusions Women with multimorbidity are an “at-risk” subgroup for severe SARS-CoV-2 infection and greater likelihood of both placental damage and perinatal hypoxic-ischemic events. These results suggest that patient education, SARS-CoV-2 disease monitoring and preventive measures would be of benefit to this group.

Objectives To estimate factors affecting survival in prenatally diagnosed omphalocele, factors predicting genetic abnormalities, and association of omphalocele and specific groups of anomalies. Methods A retrospective observational study was performed, analyzing data of all omphalocele cases diagnosed prenatally in the perinatology clinic of a referral center. Demographic data, characteristics of the omphalocele (size, content, associated anomalies), results of genetic testing, pregnancy outcomes and postnatal outcomes were analyzed. Results Sixty-nine fetuses with omphalocele were included. The prevalence of omphalocele in livebirth was 0.007 %. Overall survival during the study period was 73.9 %. Twenty-eight (71.7 %) out of 39 cases with associated anomalies who were born live, survived, whereas survival was 85.7 % in the isolated cases. The most common anomaly associated with omphalocele were cardiac defects with 42 %; followed by placental or umbilical cord anomalies (28.9 %), skeletal defects (27.5), genitourinary anomalies (20.2 %), central nervous system (18.8 %) and facial anomalies (7.2 %), respectively. Eighty-five percent of the fetuses had at least one additional anomaly or ultrasound finding. Skeletal abnormalities and staged surgical repair of omphalocele were associated with survival. Associated skeletal anomalies and staged repair significantly increase the risk of postnatal death (OR: 4.6 95 % CI (1.1–19.5) and (OR: 10.3 95 % CI (1.6–63.9), respectively). Conclusions Associated skeletal abnormalities and staged surgical repair are negatively associated with postnatal survival.

Objectives Abnormal body mass index (BMI) during pregnancy, a growing public health concern, increases maternal and neonatal complications. This study aimed to investigate the impact of abnormal BMI on perinatal outcomes compared to normal BMI. Methods A total of 14,624 women having singleton births were categorized as underweight (BMI<18.5 kg/m 2 ), overweight (25.0–29.9 kg/m 2 ), obesity class I (30.0–34.9 kg/m 2 ), obesity class II (35.0–39.9 kg/m 2 ), and obesity class III (≥40.0 kg/m 2 ) and compared to those with normal BMI (18.5–24.9 kg/m 2 ). Outcomes included gestational diabetes (GDM), gestational hypertension (GHT), postpartum haemorrhage (PPH), cesarean delivery (CD), preterm birth (PTB), low birth weight (LBW), congenital anomalies and neonatal intensive care unit admission. Results Women with increasing BMI had increasingly higher odds of developing specific adverse outcomes, the highest being in the class III obesity group (GDM-aOR 2.71, 95 % CI 2.25–3.27, p<0.001, GHT-aOR 5.32 95 % CI 3.49–8.11, p<0.001, CD-aOR 2.33 95 % CI 1.85–2.94, p<0.001, PPH-aOR 1.77 95 % CI 1.35–2.33, p<0.001). On the other hand, being underweight during pregnancy was associated with increased odds of PTB (aOR 2.09, 95 % CI 1.37–3.20, p=0.001), LBW (OR 1.88, 95 % CI 1.27–2.79, p=0.002) and congenital anomalies (aOR 2.52 95 % CI 1.12–5.64, p=0.025). Majority in the underweight category gained less than expected gestational weight gain during the pregnancy. Conclusions The findings of this study have important implications for the clinical management of pregnant women with abnormal BMI. Interventions to improve maternal and neonatal outcomes must focus on enhancing pre-pregnancy BMI and maintaining adequate gestational weight gain.

Objectives To describe embryonic and fetal tiny pericardial fluid collections (PFCs) using transvaginal sonography and HDlive Silhouette at less than 12 weeks of gestation. Methods During an 8-month period from November 2021 to June 2022, one-hundred and thirty transvaginal scans were performed for first-trimester dating, and eleven tiny PFCs of the embryo or fetus were identified at 8+4 – 11+3 weeks of gestation (three at 8, six at 9, and two at 11 weeks). HDlive Silhouette features of PFC were evaluated. Their clinical characteristics and outcomes were also investigated. Results The incidence of tiny PFCs was 8.5 % at less than 12 weeks of gestation. The mean gestational age at the initial examination was 9.5 weeks (SD: ± 0.9). The mean crown-rump length was 25.0 mm (SD: ± 8.5). The mean PFC dimension was 0.8 mm (range: 0.5–1.3, SD: ± 0.2). Pleural effusion was associated with 3 out of 11 PFCs (27.2 %). Ascites was noted in 2 cases (18.2 %). Skin edema was identified in only in 1 case (0.09 %). There was no arrhythmia. Tiny PFC could also be depicted using HDlive Silhouette. First-trimester fetal ultrasound scans at 11 – 13+6 weeks showed no abnormal findings. PFCs resolved until 13 weeks of gestation (Mean: 12 weeks, SD: ± 1.2). All PFC pregnancies resulted in healthy neonates. Conclusions The incidence of tiny PFCs was relatively high in early pregnancy. HDlive Silhouette can depict tiny PFCs of the embryo. Tiny PFCs in early gestation are transient, benign findings in utero .

Objectives To develop charts for fetal brain cortical structures following a proposed standardized methodology and using quantile regression. Methods Prospective cross-sectional study including 344 low-risk singleton pregnancies between 19 and 34 weeks of gestation. The depth of Sylvian (SF), Parieto-occipital (POF) and Calcarine fissures (CF) were measured on ultrasound images using a standardized technique and their changes were evaluated by quantile regression as a function of gestational age (GA) interval or head circumference (HC). Results The measurements of SF, POF and CF depth significantly increased with gestation. Linear models better described the changes of cortical variables with GA and HC. When the fit of sulci depth with GA and HC were compared, a close relationship was highlighted for the latter variable. Conclusions We provided prospective charts of fetal cortical development using quantile regression and following a strict standardized methodology These new charts may help in better identifying cases at higher risk of abnormal cortical neurodevelopment.

Objectives To understand the effect of 50-g oral glucose tolerance test (OGTT) on fetal celiac artery and superior mesenteric artery (SMA) Doppler parameters. Methods A total of 43 healthy pregnant women followed in our hospital were included in the study. All Doppler parameters of the celiac artery and SMA (peak systolic velocity (PSV); pulsatility index (PI); resistance index (RI); systolic/diastolic ratio (SD); time average maximum velocity (TAMAX)) were obtained by ultrasonography before and 1 h after OGTT. Results The mean PSV value of the celiac artery decreased statistically significantly after OGTT (37.29 ± 11.96 cm/s; 29.51 ± 10.07 cm/s; p=0.002). While the mean of the PI was 2.09 ± 0.57 before the test, it was found to be 1.84 ± 0.64 after the test (p=0.027). Mean PSV (39.82 ± 13.07 cm/s; 35.19 ± 15.27 cm/s; p=0.104) and PI (2.21 ± 0.65; 2.11 ± 0.80; p=0.375) values of SMA were also found to be decreased without statistically significancy. Conclusions The data obtained from our study reveals that the PSV and PI values of celiac artery and SMA slightly decrease after OGTT.

Objectives Hypoxic ischaemic encephalopathy (HIE) is associated with oxidative stress. A potential marker of oxidative damage is carboxyhaemoglobin (COHb) which is the product of the reaction between carbon monoxide and haemoglobin and is routinely assessed on blood gas analysis. Our objective was to test the hypothesis that higher COHb levels would be associated with worse outcomes in infants treated for HIE. Methods A retrospective, observational study was performed of all infants who received whole body hypothermia for HIE at a tertiary neonatal intensive care unit between January 2018 and August 2021. For each participating infant, the highest COHb level per day was recorded for days one, three and five after birth. Results During the study period, 67 infants with a median (IQR) gestational age of 40 (38–41) weeks underwent therapeutic hypothermia for HIE. The median (IQR) COHb level on day three was higher in infants without electroencephalographic seizures (1.4 [1.1–1.4] %) compared with infants with seizures (1.1 [0.9–1.3] %, p=0.024). The median (IQR) COHb on day five was higher in infants without MRI brain abnormalities (1.4 [1.2–1.7] %) compared with infants with MRI abnormalities (1.2 [1.0–1.4] %, p=0.032). The COHb level was not significantly different between the nine infants who died compared to the infants who survived. Conclusions COHb levels were higher in infants with HIE without seizures and in those with normal MRI brain examinations. We suggest that carbon monoxide has a potential protective role in HIE.

Objectives Congenital diaphragmatic hernia (CDH) is a congenital malformation in which the diaphragm and lungs are underdeveloped, leading to cardiorespiratory and other problems. This study aimed to explore professionals’ views regarding prenatal counselling in CDH. Methods A qualitative study was performed among healthcare professionals involved in the care of CDH patients in Radboud university medical center Amalia Children’s Hospital. Semi-structured interviews were conducted until saturation was achieved. Transcripts were qualitatively analysed to gain insight into professionals’ views regarding counselling. Results Eighteen professionals with various backgrounds were included. The professionals agreed that the first counselling session should be soon after diagnosis and additional sessions should be offered. Concerning counselling content, participants considered explanation of the diagnosis, prognosis, short- and long-term consequences, treatment options and practical aspects important. As for decision-making about possible termination of pregnancy, all professionals emphasised the importance of the parental role, but the preferred parental involvement varied. Regarding practical aspects, preferred counsellors were a neonatologist, obstetrician, paediatric surgeon and/or medical social worker. Participants emphasised that the counselling should be adjusted to parents’ needs. Conclusions This study gained insight into professionals’ views regarding the timeline, content, decision-making process, and practical aspects of prenatal counselling in CDH.