Volume 49, Issue 5

Background Neonatal lupus erythematosus is an autoimmune disease acquired during fetal life as a result of transplacental passage of maternal anti-Sjögren’s-syndrome-related antigen A (anti-SSA/Ro), anti-Sjögren’s-syndrome-related antigen B (anti-SSB/La) or anti-U1 ribonucleoprotein (anti-U1-RNP) antinuclear autoantibodies. Contents Clinical manifestations include skin lesions, congenital heart block, hepatobiliary involvement and cytopenias. Most of the disorders disappear spontaneously after clearance of maternal antibodies. Cardiac symptoms, however, are not self-resolving and often pacemaker implantation is required. Diagnosis is based on clinical presentation and the presence of typical antibodies in the mother’s or infant’s serum. Outlook Neonatal lupus erythematosus may develop in children born to anti-SSA/Ro or anti-SSB/La women with various systemic connective tissue diseases. However, in half of the cases, the mother is asymptomatic, which may delay the diagnosis and have negative impact on the child’s prognosis. Testing for antinuclear antibodies should be considered in every pregnant woman since early treatment with hydroxychloroquine or intravenous immunoglobulin (IVIG) has proven to be effective in preventing congenital heart block.

Objectives Although current guidelines advice to screen for asymptomatic bacteriuria during pregnancy, little is known about the best moment of testing. The goal of this study is to analyze the optimal timing (first vs. second trimester) to screen for asymptomatic bacteriuria during pregnancy. Methods A retrospective cohort analysis, comparing patients that were screened for asymptomatic bacteriuria in the first vs. second trimester was performed. The main question was to compare the rate of positive urinary culture in both trimesters. Study included patients all followed a prenatal consultation at the University Hospital of Brussels between 2012 and 2017. Other outcomes considered were the nature of identified germs, treatments, possible risk and confounding factors (age, BMI, gravidity-parity-abortus [GPA], type of conception, ethnicity, education, prior urinary tract infection (UTI), diabetes, hypertension, prior preterm delivery and sickle cell disease) and complications (UTI, preterm delivery, preterm rupture of the membranes and chorio-amnionitis). Results A total of 2,005 consecutive files were reviewed, 655 concerned patients screened during the first trimester group and 1,350 in the second trimester group. Asymptomatic bacteriuria was present in only 71 cases (3.54%), 23 in the first trimester group (3.50%) and 48 in the second trimester group (3.55%). Escherichia coli was the most frequently identified germ (37 cases (1.8%), 14 in the first trimester group and 23 in the second trimester group). Our logistic regression analysis shows no statistical difference according to the moment the urinary culture was done for the presence of asymptomatic bacteriuria ( E. coli or others), for its association with hospitalization for pyelonephritis, preterm contractions, preterm pre-labor rupture of the membranes (PPROM) and/or preterm delivery. Conclusions If recommendations remain to screen for asymptomatic bacteriuria at least once during pregnancy, this study indicates that the moment of testing (first vs. second trimester) has no clinical impact on obstetrical outcomes.

Objectives An international diagnostic criterion for amniotic fluid embolism (AFE) diagnosis has recently been published. Data regarding subsequent pregnancies is scarce. We sought to implement recent diagnostic criteria and detail subsequent pregnancies in survivors. Methods A case series of all suspected AFE cases at a tertiary medical center between 2003 and 2018 is presented. Cases meeting the diagnostic criteria for AFE were included. Clinical presentation, treatment, and outcomes described. Pregnancy outcomes in subsequent pregnancies in AFE survivors detailed. Results Between 2003 and 2018 14 women were clinically suspected with AFE and 12 of them (85.71%) met the diagnostic criteria for AFE. Three cases occurred during midtrimester dilation and evacuation procedures, and the remaining occurred in the antepartum period. Of the antepartum cases, mode of delivery was cesarean delivery or vacuum extraction for expedited delivery due to presentation of AFE in 8/9 cases (88.88%). Clinical presentation included cardiovascular collapse, respiratory distress and disseminated intravascular coagulopathy (DIC). Heart failure of varying severity was diagnosed in 75% (9/12) cases. Composite maternal morbidity was 5/12 (41.66%), without cases of maternal mortality. 11 subsequent pregnancies occurred in four AFE survivors. Pregnant women were followed by a high-risk pregnancy specialist and multidisciplinary team if pregnancy continued beyond the early second trimester. Six pregnancies resulted in a term delivery. No recurrences of AFE were documented. Conclusions Use of a diagnostic criterion for diagnosis of AFE results in a more precise diagnosis of AFE. Nevertheless, the accuracy of clinical diagnosis is still high. Subsequent pregnancies were not associated with AFE recurrence.

Objectives To investigate the association between selected single nucleotide polymorphisms (SNPs) with cervical insufficiency and its relationship with obstetric history. Methods Twenty-eight women with cervical insufficiency (case group) and 29 non-pregnant women (control group) were included. The SNPs sequenced included rs2586490 in collagen type I alpha 1 chain ( COL1A1 ), rs1882435 in collagen type IV alpha 3 chain ( COL4A3 ), rs2277698 in metallopeptidase inhibitor 2 ( TIMP2 ), and rs1800468 in transforming growth factor beta 1 ( TGFB1 ). Results We found a higher frequency of the normal allele in the control group (65.5%) and the homozygous mutated genotype in the case group (64.3%) for rs2586490 in COL1A1 (p=0.023). An unplanned finding in the cervical insufficiency group was a higher gestational age of delivery (median≥38 weeks) in the mutated allele than in the wild-type genotype (median of 28.2 weeks) for rs2857396, which is also in the COL1A1 gene (p=0.011). Conclusions The findings of the present study corroborate the hypothesis that cervical insufficiency has a genetic component and probably involves genes encoding proteins in the extracellular matrix, in addition to inflammatory processes.

Objectives We aim to study the association of maternal age with maternal and neonatal complications in twin pregnancies. Methods A retrospective cohort study of dichorionic–diamniotic twin pregnancies stratified into three groups according to maternal age (“A” <25, “B” 25–34 and “C” 35–44 years old). Outcome measures included pregnancy, delivery and neonatal complications. A sub-analysis of in vitro fertilization pregnancies only was conducted. Results Compared with younger women (groups A [n=65] and B [n=783]), older women [group C (n=392)] demonstrated significantly higher rates of gestational diabetes mellitus (B 6.6% vs. A 0%, p =0.027, C 10.2% vs. B 6.6%, p =0.032), were more likely to undergo cesarean deliveries (C 66.6%, B 57.6%, A 52.3%, p =0.007), and were at increased risk of having more than 20% difference in weight between the twins (C 24.5%, B 17.4%, A 16.9%, p =0.013). Other outcomes, including preeclampsia, did not differ between the groups. A sub-analysis of the in vitro fertilization only pregnancies was performed. Compared with younger women (groups A [n=18] and B [n=388]), older women (group C [n=230]) underwent more cesarean deliveries (p=0.004), and had more than 20% difference in weight between the twins (p<0.004). Other outcomes, including gestational diabetes mellitus rates and preeclampsia, did not differ between the groups. Conclusions Women at advanced maternal age with dichorionic twin pregnancies had significantly higher rates of gestational diabetes mellitus, cesarean deliveries and fetal weight discordancy as compared with younger women. In contrast, the incidence of preeclampsia was not affected by maternal age.

Objectives The impedance cardiography (ICG) technique measures the variation of impedance in the thorax due to the physical contractile activity of the heart. Twin pregnancy is characterized by greater maternal hemodynamic changes than a singleton pregnancy. Methods In a study on 121 pregnant women in the last trimester we performed ICG, evaluating the following hemodynamic parameters: stroke volume, heart rate, cardiac output, ventricular ejection time, left ventricular ejection time, thoracic impedance, and systemic vascular resistance. Results The study included singleton and twin pregnancies. Heart rate values in women with single fetus was lower than in those carrying twins (85 vs. 100 beats/min, p=0.021) as were the stroke volume values (64 vs. 83 mL, p=0.010) and the cardiac output (p<0.0001). Systemic vascular resistance decreased in twin pregnancies compared to singleton pregnancy (p=0.023). Conclusions ICG studies are rare, and the validation of their results is an ongoing process. However, the ICG technique is applicable in the third trimester of pregnancy and can yield important information regarding the hemodynamic profile of singleton and twin pregnancies, revealing maternal heart changes specific to twin pregnancies.

Objectives (A) To introduce a new technique for vaginal fluid sampling (biocompatible synthetic fiber sponge) and (B) evaluate the collected vaginal fluid interleukine-6 (IL-6 vag )-concentration as a new diagnostic tool for daily monitoring of intrauterine inflammation after preterm premature rupture of membranes (PPROM). Secondary objectives were to compare the potential to predict an intrauterine inflammation with established inflammation parameters (e.g., maternal white blood cell count). Methods This prospective clinical case-control diagnostic accuracy multicenter study was performed with women after PPROM (gestational age 24.0/7 – 34.0/7 weeks). Sampling of vaginal fluid was performed once daily. IL-6 vag was determined by electrochemiluminescence-immunoassay-kit. Neonatal outcome and placental histology results were used to retrospectively allocate the cohort into two subgroups: 1) inflammation and 2) no inflammation (controls). Results A total of 37 cases were included in the final analysis. (A): Measurement of IL-6 was successful in 86% of 172 vaginal fluid samples. (B): Median concentration of IL-6 vag in the last vaginal fluid sample before delivery was significantly higher within the inflammation group (17,085 pg/mL) compared to the controls (1,888 pg/mL; p=0.01). By Youden’s index an optimal cut-off for prediction an intrauterine inflammation was: 6,417 pg/mL. Two days before delivery, in contrast to all other parameters IL-6 vag remained the only parameter with a sufficient AUC of 0.877, p<0.001, 95%CI [0.670–1.000]. Conclusions This study established a new technique for vaginal fluid sampling, which permits assessment of IL-6 vag concentration noninvasively in clinical daily routine monitoring.

Objectives To determine the association between the number of pulls during vacuum-assisted deliver and neonatal and maternal complications. Methods This was a single-center observational study using a cohort of pregnancies who underwent vacuum-assisted delivery from 2013 to 2020. We excluded pregnancies transitioning to cesarean section after a failed attempt at vacuum-assisted delivery. The number of pulls to deliver the neonate was categorized into 1, 2, 3, and ≥4 pulls. We used logistic regression models to investigate the association between the number of pulls and neonatal intensive care unit (NICU) admission and maternal composite outcome (severe perineal laceration, cervical laceration, transfusion, and postpartum hemorrhage ≥500 mL). Results We extracted 480 vacuum-assisted deliveries among 7,321 vaginal deliveries. The proportion of pregnancies receiving 1, 2, 3, or ≥4 pulls were 51.9, 28.3, 10.8, and 9.0%, respectively. The crude prevalence of NICU admission with 1, 2, 3, and ≥4 pulls were 10.8, 16.2, 15.4, and 27.9%, respectively. The prevalence of NICU admission, amount of postpartum hemorrhage, and postpartum hemorrhage ≥500 mL were significantly different between the four groups. Multivariable logistic regression analysis found the prevalence of NICU admission in the ≥4 pulls group was significantly higher compared with the 1 pull group (adjusted odds ratio, 3.3; 95% confidence interval, 1.4–7.8). In contrast, maternal complications were not significantly associated with the number of pulls. Conclusions Vacuum-assisted delivery with four or more pulls was significantly associated with an increased risk of NICU admission. However, the number of pulls was not associated with maternal complications.

Objectives The subject of our analysis is the influence of umbilical cord collision around the fetal neck on the fetal heart function and cerebral circulation. Methods Our study was carried out on a group of 115 fetuses from single pregnancies with physiological course, during the 15th to 40th week of pregnancy. In our analysis, we examined the following parameters: Tei index for right ventricle, Tei index for left ventricle with Tei index components: isovolumetric contraction time, isovolumetric relaxation time, ejection time and cardiothoracic area ratio, middle cerebral artery peak systolic velocity (PS MCA), middle cerebral artery pulsatility index (PI MCA). Gestational age in our study was: 28+2±34. The study group of patients with fetal umbilical cord around neck group (fUCAN) included 38 fetuses (20 males, 18 females). The control group of patients with no fetal umbilical cord around neck group (NfUCAN) included 77 fetuses (43 males, 34 females). Results In our study, we found no significant differences in the values obtained: Tei LV in fUCAN: 0.5±0.1 vs. in NfUCAN: 0.5±0.1; p=0.42), Tei RV in fUCAN: 0.5±0.2 vs. in NfUCAN: 0.4±0.1; (p=0.2). Tricuspid valve regurgitation-TR was observed with the following frequency: fUCAN: 7/38, 18% vs. NfUCAN: 13/77, 17%; p=0.8. MCA PS in study fUCAN group was significantly higher than in NfUCAN (40.2±11.5 vs. 32.5±9.5; p=0.003), although other hemodynamic and clinical variables did not differ between the study and control groups. Conclusions The fetal nuchal umbilical cord collision did not affect the fetal heart function expressed as Tei index, at the time of fetal heart examination (at mean gestational age 29+4 weeks). The fUCAN group presented elevated PS MCA, which was not related to other hemodynamic and clinical variables between the study and control groups.

Objectives The development of the artificial intelligence (AI) classifier to recognize fetal facial expressions that are considered as being related to the brain development of fetuses as a retrospective, non-interventional pilot study. Methods Images of fetal faces with sonography obtained from outpatient pregnant women with a singleton fetus were enrolled in routine conventional practice from 19 to 38 weeks of gestation from January 1, 2020, to September 30, 2020, with completely de-identified data. The images were classified into seven categories, such as eye blinking, mouthing, face without any expression, scowling, smiling, tongue expulsion, and yawning. The category in which the number of fetuses was less than 10 was eliminated before preparation. Next, we created a deep learning AI classifier with the data. Statistical values such as accuracy for the test dataset and the AI confidence score profiles for each category per image for all data were obtained. Results The number of fetuses/images in the rated categories were 14/147, 23/302, 33/320, 8/55, and 10/72 for eye blinking, mouthing, face without any expression, scowling, and yawning, respectively. The accuracy of the AI fetal facial expression for the entire test data set was 0.985. The accuracy/sensitivity/specificity values were 0.996/0.993/1.000, 0.992/0.986/1.000, 0.985/1.000/0.979, 0.996/0.888/1.000, and 1.000/1.000/1.000 for the eye blinking, mouthing, face without any expression, scowling categories, and yawning, respectively. Conclusions The AI classifier has the potential to objectively classify fetal facial expressions. AI can advance fetal brain development research using ultrasound.

Objectives The aim of this study was to investigate the correlation between fetal thymus size measured during first-trimester screening and chromosomal anomalies. Methods This study is a retrospective evaluation, in which the anterior-posterior diameter of the thymus in a midsagittal plane was measured in first-trimester ultrasound between 11 +0 and 13 +6 weeks of gestation in 168 fetuses with chromosomal anomalies (study group) and 593 healthy fetuses (control group). The included cases were subdivided into six groups: (1) trisomy 21, (2) trisomy 18, (3) trisomy 13, (4) Turner syndrome, (5) triploidy and (6) normal controls. Thymus size measurements were adjusted to the week of gestation, which was determined by ultrasound using crown-rump-length (CRL), by calculating a ratio between CRL and thymus size (CRL-thymus-ratio). Each study group was compared with the control group separately. Results Thymus size in fetuses affected by trisomy 18 or trisomy 13 was noticeably smaller compared to the control group (1.4 mm [1.3, 1.5] and 1.3 mm [1.2, 1.4] vs. 1.8 mm [1.6, 2.1]; all p<0.001; respectively). The thymus size of fetuses with trisomy 21 and Turner syndrome did not differ from healthy fetuses. Between the CRL-thymus-ratios of the separate study groups no statistically noticeable differences could be found. Conclusions Fetal thymus size appeared to be smaller in pregnancies affected by trisomy 18 and trisomy 13. The predictive value of fetal thymus size in first-trimester screening should be evaluated prospectively.

Objectives We aimed to compare gender difference on sizes of some structures in the brain of normal male and female fetuses between 20 and 22 week gestations. Methods A total of 300 female and 300 male singleton pregnancies with low risk were included in the study. Biparietal diameter, head circumference, transcerebellar diameter, cisterna magna, nuchal fold thickness, anterior and posterior horn of lateral ventricles, length and width of cavum septum pellucidum were measured transabdominally. Mean±SD values were calculated and comparison of measurements were done between male and female fetuses. Kolmogorov–Smirnov and independent samples t -test were used for statistical analysis. A value of p<0.05 were accepted as statistically significant. Results We determined statistically significant difference in sizes of some structures of the brain of male and female fetuses. Mean±SD value of cavum septi pellucidi width was 3.38±0.61 and 3.85±0.96 in female and males, respectively (p<0.05). Male fetuses were also found to have larger anterior (1.92±0.30 vs. 1.58±0.26, p<0.0001) and posterior horn of lateral ventricles (6.00±0.87 vs. 5.53±1.17, p<0.05). Conclusions Difference in sizes of some structures of the brain starts in fetal life. This finding may be important in evaluating the intracranial structures more precisely. These results may also give a contribution to the understanding physiological and pathologic differences between males and females.

Objectives Asylum seekers have been highlighted as a particularly vulnerable group of expectant mothers due to complex medical and psychosocial needs, as well as the difficulties they may face in accessing care. Our aim was to examine if there were differences in the antenatal care and perinatal outcomes for asylum seeking women when compared to age- and ethnicity-matched controls delivering at the same hospital. Methods Two age- and ethnicity-matched non-asylum seeking controls were identified for each asylum-seeking woman. Electronic patient records were analysed to determine the amount of antenatal care received and neonatal outcomes. Results Thirty-four asylum-seeking women were identified who had term born infants. The median number of antenatal care episodes at the delivering hospital was significantly fewer amongst asylum-seeking women compared to controls (three vs. nine, p<0.0001). The median number of antenatal ultrasound examinations at the delivering hospital amongst asylum-seeking women was one (IQR 1–2), compared to three (IQR 3–4) in the controls (p<0.0001). The postnatal length of stay was significantly longer for infants of asylum-seeking women (median three vs. two days, p=0.002). Thirty-seven percent of asylum seeking women but none of the controls required assistance from social services. There was a significant correlation between antenatal and postnatal costs for asylum seeking women (r=0.373, p=0.042), but not for controls (r=0.171, p=0.181). Conclusions The increased postnatal length of stay in the infants of asylum seeking mothers may reflect their mother’s reduced antenatal care and hence insufficient discharge planning for mothers and infants with increased social needs.

Objectives The maturation of the sympathetic nervous system (SNS) occurs steadily throughout gestation while the myelinated vagus has accelerated maturation periods, between 25 and 32 weeks of gestation and a further increase around 37–38 weeks of gestation. The aim was to quantify the cardiac autonomic regulation maturation, as a function of gestational age (GA) in a cohort of low risk preterm infants born between 28 and 32 weeks of gestation by assessing heart rate variability (HRV) at week 32, and at week 35 postmenstrual age (PMA). Methods Forty preterm infants were recruited, 24 h recordings of breathing rate and RR intervals were obtained at week 32 and week 35 PMA. Results A significant difference was noted between preterm infants born before 32 weeks GA and preterm infants born at week 32; the latter present higher HRV values throughout the follow-up period. No significant change over time was noted for the parasympathetic HRV measures while a significant increase was found in the sympathetic system. Moreover, a significant interaction effect of time and system was found, the increase in values of the sympathetic system over time was significantly larger than the change noted in the vagal HRV measures. Conclusions Given the beneficial influence of vagal tone on health and developmental outcomes in preterm infants, the findings of the current study highlight the need for further studies on the impact of specifics gestational age on vagal development and later assessing interventions associate with its continue development and maturation at these specific periods.

Objectives Infants receiving care from neonatal intensive care unit (NICU) can develop chronic problems and be transferred to a paediatric intensive care unit (PICU) for on-going care. There is concern that such infants may take up a large amount of PICU resource, but this is not evidence based. We determined the impact of such transfers. Methods We reviewed 10 years of NICU admissions to two tertiary PICUs, which had approximately 12,000 admissions during that period. Results Sixty-seven infants, gestational age at birth 34.7 (IQR 27.1–38.8) weeks and postnatal age on transfer 81 (IQR 9–144) days were admitted from NICUs. The median (IQR) length of stay was 12 (4–41) days. The 19 infants born <28 weeks of gestation had a greater median length of stay (32, range IQR 10–93 days) than more mature born infants (7.5, IQR 4–26 days) (p=0.003). The median cost of PICU stay for NICU transfers was £23,800 (range 1,205–1,034,000) per baby. The total cost of care for infants transferred from NICUs was £6,457,955. Conclusions Infants transferred from NICUs were a small proportion of PICU admissions but, particularly those born <28 weeks of gestation, had prolonged stays which needs to be considered when determining bed capacity.