Prenatal Diagnosis of Esophageal Atresia - Performance and Consequences.

BACKGROUND: Prenatal diagnosis of congenital malformations is considered favorable. Esophageal atresia (EA) is prenatally detected in 10-40% of patients. The aims of our study were to assess factors influencing the prenatal detection rate and to study the outcome in EA patients with and without prenatal diagnosis. METHOD: We included 136 patients in two time periods, group 1 (1996-2002, n = 68) and group 2 (2014-2020, n = 68). We registered clinical variables; prenatal signs, perinatal and postnatal outcome from the electronic patient record. RESULTS: Twenty-five patients (18%) had a prenatal diagnosis of EA, significantly more during 2014-2020 (28%), than during 1996-2002 (9%). Patients with EA type A or B and with associated anomalies had increased likelihood of prenatal diagnosis, odds ratio (OR) 9.00 (1.99-40.69) and 3.53 (1.24-10.06), respectively. Among the 25 patients with prenatal diagnosis all had polyhydramnios and 16 had small/absent stomach. Prenatally diagnosed patients arrived significantly earlier at the surgical unit (median 2 h (2 h-1 days) vs 21 h (2 h-1275 days)), had more delayed primary anastomosis (OR 8.80 (2.68-28.92)) and anastomotic stricture (OR 3.11 (1.20-8.04)), longer length of stay (median 62 days (11-212 days) vs 20 days (2-270 days)) and longer time on ventilator (median 5 days (1-25 days) vs 1.5 days (0.5-33 days)) compared to patients without prenatal diagnosis. In multivariate analysis prenatal diagnosis predicts length of stay. CONCLUSION: Prenatally diagnosed EA patients have more; type A and B malformations, associated anomalies and neonatal morbidity. Consequences of the assumed benefits of prenatal diagnosis; opportunity of early arrival to surgical care and prenatal counselling, must be further studied.

Diagnosing atopic dermatitis in infancy using established diagnostic criteria: a cohort study.

BACKGROUND: Diagnosing atopic dermatitis (AD) in infants is challenging. OBJECTIVES: To determine the incidence and persistence of eczema and AD in infants using the UK Working Party (UKWP) and Hanifin and Rajka (H&R) criteria. METHODS: A cohort of 1834 infants was examined clinically at 3, 6 and 12 months of age. AD was diagnosed by UKWP (3, 6 and 12 months) and H&R (12 months) criteria. Logistic regression models were used to assess the relationship between AD and eczema. RESULTS: Eczema was observed in 628 (34·2%) infants (n = 240, n = 359 and n = 329 at 3, 6 and 12 months, respectively), with AD diagnosed in 212 (33·7%) infants with any eczema and in 64/78 (82%) infants with eczema at all three visits. The odds of AD were lower with first presentation of eczema at 6 [odds ratio (OR) 0·33, 95% confidence interval (CI) 0·22-0·48] or 12 months (OR 0·49, 95% CI 0·32-0·74) than at 3 months, and higher in infants with eczema at three (OR 23·1, 95% CI 12·3-43·6) or two (OR 6·5, 95% CI 4·3-9·9) visits vs. one visit only. At 12 months, 156/329 (47·4%) fulfilled the UKWP and/or H&R criteria; 27 (8%) fulfilled the UKWP criteria only and 65 (20%) only the H&R criteria. Of the 129 infants who fulfilled the H&R criteria, 44 (34·1%) did not meet the itch criterion. CONCLUSIONS: Used in combination and at multiple timepoints, the UKWP and H&R criteria for AD may be useful in clinical research but may have limited value in most other clinical settings.

Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy.

BACKGROUND: Loss-of-function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. OBJECTIVES: To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy. METHODS: FLG mutations were analysed in 1836 infants in the Scandinavian population-based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age. RESULTS: FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3 g m-2  h-1 ) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95-4·28; P < 0·001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69-10·68) vs. 8·24 (95% CI 7·97-8·15), P < 0·01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25-2·80; P = 0·002 and OR 2·44, 95% CI 1·51-3·95; P < 0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04-2·22; P = 0·028 and OR 1·74, 95% CI 1·17-2·57; P = 0·005). FLG mutations were associated with eczema and AD in infancy. CONCLUSIONS: FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months.

Uterine artery Doppler flow velocity waveform analysis following uterine fibroid embolisation.

The objective was to evaluate the relation of uterine artery Doppler flow pulsatility index (PI) with total uterine volume reduction following bilateral embolisation of uterine fibroids by injection of polyvinyl alcohol particles. Doppler flow velocity was examined before and within 8 days after embolisation (n = 13). Uterine size was assessed by magnetic resonance imaging (MRI) before, and at 3 and 6 months after, the procedure. Mean PI values (mean of right and left side) obtained before embolisation were negatively related to uterine size (r = -0.68, p = 0.010) but not to uterine volume reduction after the procedure. Mean PI values after the procedure were related to the percentage decrease in uterine volume both at 3 (r = 0.74, p = 0.004) and 6 months (p = 0.73, p = 0.005). Doppler ultrasound measures of the uterine arteries may be used to evaluate reduction of uterine size following fibroid embolisation.

IFPA Meeting 2011 workshop report II: Angiogenic signaling and regulation of fetal endothelial function; placental and fetal circulation and growth; spiral artery remodeling.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2011 there were twelve themed workshops, three of which are summarized in this report. These workshops related to vascular systems and circulation in the mother, placenta and fetus, and were divided in to 1) angiogenic signaling and regulation of fetal endothelial function; 2) placental and fetal circulation and growth; 3) spiral artery remodeling.

Psychological distress after recent detection of fetal malformation: short-term effect on second-trimester uteroplacental and fetoplacental circulation.

We examined the short-term effect of severe maternal psychological distress on the placental circulation in second trimester in a prospective observational study. In 86 pregnant women with a newly detected fetal malformation, and 98 women with normal ultrasound findings, distress was assessed using the Impact of Event Scale and the General Health Questionnaire-28. Uterine and umbilical artery pulsatility indices, notching and heart rates were measured by Doppler ultrasound. Psychological distress was high in the anomaly group, but circulatory outcome measures did not differ between groups. Multiple regression analyses did not show an increase in circulatory resistance measures even at high distress levels.

Acute maternal social dysfunction, health perception and psychological distress after ultrasonographic detection of a fetal structural anomaly.

OBJECTIVES: To predict acute psychological distress in pregnant women following detection of a fetal structural anomaly by ultrasonography, and to relate these findings to a comparison group. DESIGN: A prospective, observational study. SETTING: Tertiary referral centre for fetal medicine. POPULATION: One hundred and eighty pregnant women with a fetal structural anomaly detected by ultrasound (study group) and 111 with normal ultrasound findings (comparison group) were included within a week following sonographic examination after gestational age 12 weeks (inclusion period: May 2006 to February 2009). METHODS: Social dysfunction and health perception were assessed by the corresponding subscales of the General Health Questionnaire (GHQ-28). Psychological distress was assessed using the Impact of Events Scale (IES-22), Edinburgh Postnatal Depression Scale (EPDS) and the anxiety and depression subscales of the GHQ-28. Fetal anomalies were classified according to severity and diagnostic or prognostic ambiguity at the time of assessment. MAIN OUTCOME MEASURES: Social dysfunction, health perception and psychological distress (intrusion, avoidance, arousal, anxiety, depression). RESULTS: The least severe anomalies with no diagnostic or prognostic ambiguity induced the lowest levels of IES intrusive distress (P = 0.025). Women included after 22 weeks of gestation (24%) reported significantly higher GHQ distress than women included earlier in pregnancy (P = 0.003). The study group had significantly higher levels of psychosocial distress than the comparison group on all psychometric endpoints. CONCLUSIONS: Psychological distress was predicted by gestational age at the time of assessment, severity of the fetal anomaly, and ambiguity concerning diagnosis or prognosis.

Limb-sparing surgery preserves more function than amputation: a Scandinavian sarcoma group study of 118 patients.

We evaluated the long-term functional outcome in 118 patients treated for osteosarcoma or Ewing's sarcoma in the extremities a minimum of five years after treatment. We also examined if impaired function influenced their quality of life and ability to work. The function was evaluated according to the Musculoskeletal Tumor Society (MSTS) score and the Toronto Extremity Salvage Score (TESS). Quality of life was assessed by using the Short Form-36 (SF-36). The mean age at follow-up was 31 years (15 to 57) and the mean follow-up was for 13 years (6 to 22). A total of 67 patients (57%) initially had limb-sparing surgery, but four had a secondary amputation. The median MSTS score was 70% (17% to 100%) and the median TESS was 89% (43% to 100%). The amputees had a significantly lower MSTS score than those with limb-sparing surgery (p < 0.001), but there was no difference for the TESS. Tumour localisation above knee level resulted in significantly lower MSTS scores and TESS (p = 0.003 and p = 0.02, respectively). There were no significant differences in quality of life between amputees and those with limb-sparing surgery except in physical functioning. Of the patients 11% (13) did not work or study. In multivariate analysis, amputation, tumour location above the knee and having muscular pain were associated with low physical function. We conclude that most of the bone tumour survivors managed well after adjustment to their physical limitations. A total of 105 are able to work and have an overall good quality of life.

Correlation between prenatal ultrasound and autopsy findings: A study of second-trimester abortions.

OBJECTIVE: To evaluate discrepancies between sonographic and autopsy findings following termination of pregnancy (TOP) in the second trimester. METHODS: This retrospective report is based on 288 consecutive second-trimester abortions carried out because of fetal malformations diagnosed by ultrasound examination at a tertiary referral center. The correlation between the results from the ultrasound and autopsy examinations was evaluated. RESULTS: Autopsy was performed in 274 cases. In 160 of the 274 pregnancies (58.4%) there was full agreement between the two examination methods. Findings detected by autopsy (in addition to those leading to termination) were not observed by ultrasonography in 86 (31.4%) of the pregnancies; of the 64 malformations that occurred, 30 (46.9%) were judged as 'detectable'. In 27 (9.9%) pregnancies, observations made by ultrasound (in addition to those leading to termination) were not confirmed at autopsy. In one pregnancy, postmortem radiology examination-but not autopsy-confirmed the ultrasound observations. No pregnancies were terminated because of false positive ultrasound observations. The correlation between ultrasound and autopsy findings was evaluated by three investigators; the inter-rater agreement was high (kappa = 0.85). CONCLUSION: Discrepancies between ultrasound and autopsy findings were observed in about 40% of the pregnancies. These discrepancies confirm the need for autopsy following TOP.

Prenatal diagnosis of congenital malformations and parental psychological distress--a prospective longitudinal cohort study.

OBJECTIVE: To test whether postnatal psychological distress in parents of babies with congenital malformations is reduced by prenatal diagnosis. METHODS: A prospective observational longitudinal cohort study was conducted at two Norwegian hospitals. We included 293 parents of babies with congenital malformations (prenatal detection rate: 36.5%) referred for neonatal surgery and 249 parents of healthy babies (comparison group). Parental psychological responses were assessed on three postnatal occasions by psychometric instruments (GHQ-28, STAI-X1, and IES). RESULTS: Significantly increased psychological distress (GHQ-28) was reported by parents who received prenatal diagnosis as compared to postnatal diagnosis; acutely 28.9 versus 24.4, P = 0.006 (comparison group: 19.6); at 6 weeks 26.8 versus 21.5, P < 0.001 (comparison group: 17.7); and at 6 months 22.6 versus 18.7, P = 0.015 (comparison group: 16.6). Mothers consistently reported higher levels of distress than fathers. Multiple linear regression analysis showed that prenatal diagnosis and being a mother significantly predicted severity of acute psychological distress. At 6 weeks and 6 months, mortality and associated anomalies were significant independent predictors of psychological distress. CONCLUSION: Controlling for other covariates, we found that prenatal diagnosis of congenital malformations was a significant independent predictor of acute parental psychological distress after birth.

Portal and umbilical venous blood supply to the liver in the human fetus near term.

OBJECTIVES: To determine the contribution of the umbilical (UV) and portal (PV) veins to blood supply to the human fetal liver in a low-risk population near term, and to assess the distribution between the left and right lobes. METHODS: In 91 low-risk pregnancies with normally grown fetuses at 36 weeks of gestation we measured the distribution of blood in the UV and PV to the right and left hepatic lobes using ultrasound imaging and Doppler techniques. RESULTS: The median (10(th), 90(th) centile) total UV return was 205 (127, 294) mL/min, of which 25% (13, 47%) was shunted through the ductus venosus, 55% (35, 66%) was distributed to the left hepatic lobe, and 20% (11, 30%) was distributed to the right hepatic lobe. While the left lobe was supplied exclusively by the UV, the right lobe received 50% (20, 70%; 37 (16, 65) mL/min) of its venous blood supply from the PV. The total venous blood supply to the liver parenchyma was 185 (114, 277) mL/min; 21% (8, 34%) came from the PV supply to the right lobe and the remainder came from the UV supply to both lobes. CONCLUSIONS: The venous supply to the left lobe is from nutrient-rich UV blood; for the right lobe, half is from UV blood and half from nutrient-poor PV blood. This watershed between the portal and umbilical venous flows to the fetal liver suggests a corresponding functional dichotomy; this may be modified by hemodynamic influences, with long-term consequences.

Doppler blood flow velocity waveforms in the fetal renal arteries: variability at proximal and distal sites in the right and left arteries.

OBJECTIVE: To investigate variability in pulsatility/resistance indices and absolute velocities of blood flow in fetal renal arteries dependent on side and sampling site within each vessel. METHODS: Doppler blood flow measurements of pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV) and end-diastolic velocity (EDV) were performed in the renal arteries of 27 fetuses between 236 and 247 days of gestation. Velocity waveforms were sampled in both the right and left renal arteries at two different sites: proximally, close to the aorta, and distally, before any major visible bifurcation of the vessels. The intraobserver variation was measured in 15 additional fetuses. RESULTS: Mean values of PI and RI were similar in the right and left renal arteries and at the proximal and distal sampling sites of these arteries. Mean PSV and EDV were higher at the proximal compared to the distal site on both sides. For all parameters the 95% limits of agreement between measurements made in the right and left arteries and at proximal and distal sites were wide but tended to be narrower for the left renal artery and at the distal site. Intraclass correlation coefficients for intraobserver variability were 0.88, 0.89, 0.83 and 0.81 for PI, RI, PSV and EDV, respectively. CONCLUSIONS: It is important to standardize the precise site at which Doppler blood flow velocity waveform measurements are made in the renal arteries of the fetus. On the basis of our observations, we suggest that the left renal artery is the preferred vessel for sampling and that measurements should be made in the renal arterial trunk away from the aorta and before any visible branches.

Influence of preeclampsia or maternal intake of omega-3 fatty acids on the vasoactive effect of prostaglandin F-two-alpha in human umbilical arteries.

The vasoactive effect of prostaglandin F(2alpha) (PGF(2alpha)) was studied in in vitro perfused human umbilical arteries following maternal dietary supplementation with omega-3 fatty acids or in pregnancies complicated by a moderate degree of preeclampsia. In most preparations PGF(2alpha) induced a biphasic pressure response with a transient dilatation followed by a constrictory response. The pressure increase was significant in both groups, but no significant differences in the constrictory response or in the proportions of preparations displaying dilatatory responses were observed when compared to appropriate control groups. In conclusion, neither preeclampsia nor dietary supplementation with cod-liver oil had any significant effect on the vasoactive response to PGF(2alpha) in umbilical cord arteries.

Doppler flow velocity waveforms and vasoactive effects of serotonin in human umbilical arteries.

The vasoactive effect of serotonin was investigated by in vitro perfusion in human umbilical arteries in which antenatal Doppler ultrasound examination revealed abnormal velocity waveforms. The results were compared to those obtained in preparations from normotensive uncomplicated term pregnancies as well as from preterm deliveries in which antenatal Doppler ultrasound examination showed normal velocity waveforms related to gestational age. Serotonin induced a monophasic vasoconstriction or a biphasic pressure response with a transient pressure decrease succeeded by a constrictory response. In all groups serotonin induced a significant (p < 0.001) constrictory response, whereas no significant differences were observed between the groups. At a serotonin dose of 10(-7) mol/l, the frequency of preparations with a biphasic pressure response was significantly smaller in the preparations with abnormal diastolic flow as compared to the term control group (5/18 vs. 13/19, p = 0.02), but not significantly different from that of the preterm control group (3/9). The umbilical arterial responsiveness to serotonin does not seem to be dependent on antenatal Doppler velocity waveforms.

Congenital diaphragmatic hernia: a meta-analysis of mortality factors.

PURPOSE: The aim of this study was to review all available studies reported in the English-language literature from 1975 through 1998, and by meta-analysis assess the importance of prenatal diagnosis, associated malformations, side of hernia, timing of surgery, and study population on mortality rates in patients with congenital diaphragmatic hernia (CDH). METHODS: One-hundred-two studies were identified, and 51 studies (2,980 patients) fulfilled the prespecified inclusion criteria. Studies were grouped according to study population into: (I) fetuses diagnosed prenatally; (II) neonates admitted to a treatment center; and (III) population-based studies. RESULTS: Pooled total mortality rate was significantly higher in category I than in category III (75.6% v 58.2%, P < .001). Pooled hidden postnatal mortality rate (deaths before admittance to a treatment center) in population-based studies was 34.9%. Prenatally diagnosed patients in both category II and III had significantly higher mortality rates than those diagnosed postnatally. Mortality rates were significantly higher among CDH infants with associated major malformations compared with isolated CDH in all 3 categories. An increased mortality rate in right-sided CDH was found in category II and III. CONCLUSIONS: Prenatal diagnosis of CDH, presence of associated major malformations, and the study population have a major influence on mortality rate. The very high mortality rate in studies of fetuses with a prenatal diagnosis of CDH should be taken into account in prenatal counselling.

Prenatal diagnosis of tracheal obstruction: possible association with maternal pertussis infection.

A fetus with the sonographic appearance of echogenic and enlarged lungs and dilated trachea and bronchi, indicating laryngotracheal obstruction, is reported. Additionally, the fetus had ascites and subcutaneous edema and the amniotic fluid volume was reduced. Doppler flow investigation of the systemic venous circulation revealed signs of heart failure, and color Doppler visualized possible increased pulmonary flow. Following termination of pregnancy, autopsy confirmed the sonographic observations and revealed a hypoplastic thymus. During the present pregnancy the mother suffered from sustained cough, and serological tests revealed acute pertussis infection. Polymerase chain reaction investigation for Bordetella pertussis in the amniotic fluid was negative. The possibilities of pertussis toxins as noxious factors and of an atypical presentation of DiGeorge anomaly are discussed.

Haplotype association and mutation analysis of the transglutaminase 1 gene for prenatal exclusion of lamellar ichthyosis.

Lamellar ichthyosis (LI) is an autosomal recessive keratinization disorder of the skin. Genetic heterogeneity has been shown for the disease and there is evidence for the involvement of the transglutaminase 1 (TGM1) gene on chromosome 14q11. We have previously identified chromosome 14q11 haplotypes associated with ichthyosis in the Norwegian population. In this paper we describe antenatal exclusion of ichthyosis in two Norwegian families by chromosome 14q11 haplotype association and direct mutation analysis. In one pregnancy, the 11-week old fetus at risk for LI was found to share only one disease-associated haplotype. A subsequent mutation analysis of the TGM1 gene in fetal DNA revealed that the fetus carried a novel 3795A-->T transversion. The affected proband was compound heterozygous for the mutations 3795A-->T and 3239G-->C resulting in an Asp430Val and a Val379Leu, respectively. In another LI family, the 11-week old fetus was found to be heterozygous for the 14q11 haplotype associated with the disease. Subsequent mutation analysis revealed that the fetus was heterozygous for the 2526A-->G transition in the splice site of intron 5 whereas the proband was homozygous for the same mutation. Our results show that haplotyping can be a useful tool for prenatal diagnosis in diseases with genetic heterogeneity.