Delayed Surgery for Perforated Appendicitis is Feasible in Children Without Compromising the Outcome in Selected Cases.

BACKGROUND AND AIM: The relationship between time to surgery and risk of postoperative complications and re-intervention has not been conclusively investigated in pediatric perforated appendicitis (PA). The aim of this study was to determine whether time to appendectomy (TTA) is a risk factor for postoperative complications and re-intervention in a cohort of children undergoing appendectomy for PA. METHODS: A total of 254 children (age: 8.7 ± 3.7 years) undergoing appendectomy for PA were retrospectively evaluated and stratified into Group I-III according to the Clavien-Dindo classification for postoperative complications (Group I n = 218, 86%; Group II n = 7, 3%; Group III n = 29, 11%). RESULTS: The TTA was comparable between all groups (group I: 8.8 ± 9.2 h; group II: 7.8 ± 5.3 h; group III: 9.5 ± 9.6 h; overall: 8.8 ± 9.1 h; p = 0.885). A C-reactive protein (CRP) value at admission of ≥128.6 mg/l indicated a higher risk for developing Grade II complications with no need for re-intervention (OR: 3.963; 95% CI: 1.810-8.678; p = 0.001) and Grade III complications with the need for re-intervention (OR: 3.346; 95% CI: 1.456-7.690; p = 0.004). This risk was independent of the TTA (OR: 1.007; 95% CI: 0.980-1.035; p = 0.613). CONCLUSIONS: Appendectomy can be delayed by an average time delay of about 9 h in children with PA without increasing the risk of postoperative complications and re-intervention, also in patients at high risk defined by the initial CRP level ≥ 128.6 mg/l. This data may support the correct risk-adjusted scheduling of surgical interventions in times of limited capacity.

[Imaging of renal tumors in children]. / Bildgebung renaler Tumoren im Kindesalter.

CLINICAL/METHODOLOGICAL ISSUE: Renal tumors in children are treated according to the guidelines of the Renal Tumor Study Group of the International Society of Pediatric Oncology (SIOP-RTSG). Nephroblastoma is the most frequent renal tumor in children. STANDARD RADIOLOGICAL METHODS: After sonography, magnetic resonance imaging (MRI) is the preferred imaging modality. The task of imaging includes differential diagnosis with the help of morphological and epidemiological criteria. Thorax computed tomography (CT) is introduced for initial staging. METHODOLOGICAL INNOVATIONS: Current studies of diffusion-weighted imaging (DWI)-MRI with analysis of the apparent diffusion coefficient (ADC) histogram indicate the potential to differentiate blastemal or anaplastic high-risk histology nephroblatoma subtypes. Imaging criteria for nephron-sparing surgery are defined and allow an individual therapy option in unilateral and especially in bilateral renal nephroblastoma. PERFORMANCE: In addition to nephroblastoma, the differential diagnosis includes congenital mesoblastic nephroma, malignant rhabdoid tumor of the kidney, clear cell sarcoma and renal cell carcinoma. The diagnosis of nephrogenic rests and nephroblastomatosis is challenging. ACHIEVEMENTS: Diagnostic standardization improves diagnosis and therapy of renal childhood tumors, and new prognostic markers may be introduced in the near future.

Measures of body fatness and height in early and mid-to-late adulthood and prostate cancer: risk and mortality in The Pooling Project of Prospective Studies of Diet and Cancer.

BACKGROUND: Advanced prostate cancer etiology is poorly understood. Few studies have examined associations of anthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk. PATIENTS AND METHODS: We carried out pooled analyses to examine associations between body fatness, height, and prostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762 advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excluding localized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Cox proportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals (CI); results were pooled using random effects models. RESULTS: No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced, advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown for BMI at baseline with advanced prostate cancer (HR = 1.30, 95% CI = 0.95-1.78) and prostate cancer mortality (HR = 1.52, 95% CI = 1.12-2.07) comparing BMI ≥35.0 kg/m2 with 21-22.9 kg/m2. When considering early adulthood and baseline BMI together, a 27% higher prostate cancer mortality risk (95% CI = 9% to 49%) was observed for men with BMI <25.0 kg/m2 in early adulthood and BMI ≥30.0 kg/m2 at baseline compared with BMI <25.0 kg/m2 in early adulthood and BMI <30.0 kg/m2 at baseline. Baseline waist circumference, comparing ≥110 cm with <90 cm, and waist-to-hip ratio, comparing ≥1.00 with <0.90, were associated with significant 14%-16% increases in high-grade prostate cancer risk and suggestive or significant 20%-39% increases in prostate cancer mortality risk. Height was associated with suggestive or significant 33%-56% risks of advanced or advanced restricted prostate cancer and prostate cancer mortality, comparing ≥1.90 m with <1.65 m. CONCLUSION: Our findings suggest that height and total and central adiposity in mid-to-later adulthood, but not early adulthood adiposity, are associated with risk of advanced forms of prostate cancer. Thus, maintenance of healthy weight may help prevent advanced prostate cancer.

Long-term outcome in displaced lateral humeral condyle fractures following internal screw fixation in children.

BACKGROUND: The aim of this study was to investigate the long-term clinical outcome following open reduction and internal screw fixation of displaced lateral condyle fractures (LCFs) of the distal humerus and compare the outcome of primary and secondary LCFs. METHODS: The clinical outcome in 31 children (mean age 5.8±2.4 years) operated for primary or secondary LCFs was retrospectively analyzed by standardized clinical examination and compared using the Mayo score, Morger score, and Patients Satisfaction score. RESULTS: The scores did not differ significantly between the primary and secondary displacement groups (Mayo score: 99.3±3.3 vs. 100±0, p=0.852; Morger score: 3.8±0.5 vs. 3.9±0.3, p=0.852; Patients Satisfaction score: 3.7±0.6 vs. 3.9±0.3, p=0.546). Deficits in range of motion and joint axis deviation were minor (< 10°) and no elbow instabilities were observed. CONCLUSIONS: Surgical treatment of a secondary displaced LCF with open reduction and internal screw fixation leads to a favorable long-term outcome. The long-term outcome is similar between primary and secondary displaced LCFs.

Hours in non-parental child care are related to language development in a longitudinal cohort study.

BACKGROUND: The effects of child care services on several domains of child development have been extensively investigated, but evidence regarding the effects of child care on language development remains inconclusive. METHODS: Within a large-scale population-based study, we examined the longitudinal associations between non-parental child care and language development from 1 to 6 years (n = 5375). RESULTS: Results showed that more hours in non-parental child care were associated with better language abilities. However, more hours in care in the first year of life were associated with less language proficiency at ages 1 to 1.5. At later ages, this effect disappeared and language proficiency increased. Furthermore, children who spent more hours in centre-based care had better language scores than children in home-based care. Ethnicity, socio-economic status, gender or parity did not change these results. CONCLUSIONS: This large, multi-ethnic study demonstrates beneficial effects of non-parental child care, particularly centre-based care, on language proficiency later in childhood.

[Lung diseases in children]. / Lungenerkrankungen im Kindesalter.

BACKGROUND: Lung diseases belong to the most common acute and chronic childhood diseases. With specific diagnostics and therapy the outcome of many congenital and acquired pulmonary diseases in children and adults can be substantially improved. OBJECTIVE: The aim of this review is the presentation and evaluation of important lung diseases in children taking recent developments into consideration. MATERIAL AND METHODS: This article presents a review of the literature on selected acute and chronic lung diseases in children and adolescents. RESULTS: Acute pneumonia remains one of the most frequent causes of mortality in children worldwide. Antibiotic treatment has reduced the morbidity and mortality in Western industrialized countries; however, the treatment of complications, such as pleural empyema and lung abscesses remains challenging. With a prevalence of 10 %, asthma has evolved into the most common chronic disease in children and adolescents in Germany. Using anti-inflammatory inhalation therapy, effective control of asthma symptoms can be achieved in most patients. Cystic fibrosis (CF) remains the most common fatal inherited disease among Caucasians. More than 90 % of the mortality and morbidity of CF are caused by an early onset and progressive chronic obstructive lung disease. Approval of the first causal mutation-specific pharmacotherapy for a subgroup of patients with CF represents a milestone in individualized therapy of lung diseases. The pathogenesis of other rare chronic lung diseases including interstitial lung diseases (ILD) is still mostly unknown. CONCLUSION: Continuous improvement in the diagnostics and therapy is crucial to further improve the management and outcome of acute and chronic lung diseases in children. Pediatric pulmonology, as an interdisciplinary subspecialty at the interface of pediatrics, pulmonology and infectious diseases, plays a key role in the translation of scientific progress into clinical practice.

Pretreatment for bilateral nephroblastomatosis is an independent risk factor for progressive disease in patients with stage V nephroblastoma.

BACKGROUND: Treatment of stage V nephroblastoma is less established and more complex than in unilateral nephroblastoma. METHODS: Retrospective analysis of 121 consecutive patients with stage V nephroblastoma registered from January 1989 to May 2005. Registration, prospective data collection and treatment were carried out within the framework of 3 consecutive SIOP/GPOH-nephroblastoma-trials. RESULTS: 19 patients had metastasis and 29 syndromes at diagnosis. 13 patients had been pretreated for bilateral nephroblastomatosis. 1 patient was not treated and 17 patients had upfront surgery. Preoperative treatment duration ranged from 1-12 weeks (n=103). 1-3 preoperative treatment-cycles resulted in average tumor-volume-reduction of 45%. 1 patient underwent bilateral nephrectomy. 52% of the patients had 2 functioning kidneys after the end of treatment. 20 patients had died after mean follow-up of 8.6 years. 5y-Progression-Free (PFS) and Overall-Survival (OS) were excellent for patients having a localized disease without pretreatment for nephroblastomatosis (5yPFS/OS: 80±4%/93±3%). Metastasis at diagnosis (51±12%/56±12%; p=0.003) and pretreatment for nephroblastomatosis (37±14%/67±13%; p<0.001) were associated with significantly poorer outcome. Cox-regression analysis revealed an independent influence of pretreatment for nephroblastomatosis, metastasis and syndromes on PFS. The latter 2 as well as anaplasia and age (<2 years or >3 years) had an independent influence on OS. CONCLUSIONS: Pretreatment for nephroblastomatosis, metastasis and syndromes are independent risk factors. 1-3 preoperative treatment-cycles are sufficient to achieve save nephron-sparing-surgery in most patients.

Results of the WIRK prospective, non-interventional observational study of recombinant activated factor VII (rFVIIa) in patients with congenital haemophilia with inhibitors and other bleeding disorders.

Recombinant activated factor VII (rFVIIa) has been available for the treatment of acute bleeding and for prevention of bleeding during surgery and invasive procedures in patients with congenital haemophilia with inhibitors (CHwI) and acquired haemophilia since 1996. The study objective was to assess the efficacy and safety of rFVIIa in patients with CHwI, acquired haemophilia, congenital FVII deficiency and Glanzmann's thrombasthenia, in a real-life clinical setting. There were no specific inclusion or exclusion criteria; participation was offered to all German haemophilia centres known to use rFVIIa to treat patients with the above indications. Data on rFVIIa use and efficacy for the treatment of acute bleeding episodes and invasive procedures were recorded. Adverse drug reactions and recurrent bleeding episodes were also monitored. In total, 64 patients (50.0% women) received rFVIIa treatment. Patients experienced 281 evaluable bleeding episodes and underwent 44 invasive procedures. In 252 of 281 (89.7%) bleeding episodes, a stop (66.5%) or a significant reduction (23.1%) in bleeding was observed. No bleeding complications were reported for 42 of 44 (95.5%) invasive procedures covered with rFVIIa. A clear positive association was observed between early initiation of rFVIIa treatment for acute bleeding and efficacy. The total cumulative dose and number of injections were 468.3 ± 545.8 µg kg(-1) and 3.6 ± 4.6 respectively. No drug-related adverse events were reported. rFVIIa use in Germany provided effective haemostatic cover without associated adverse events in the management of acute bleeds and invasive procedures across a range of bleeding disorders.

Primary lung metastases in pediatric malignant non-Wilms renal tumors: data from SIOP 93-01/GPOH and SIOP 2001/GPOH.

Malignant non-Wilms renal tumors (NWRT) are a small but relevant subgroup of renal neoplasms in children. In this study we analyzed corresponding data from the trials SIOP 93-01/GPOH and SIOP 2001/GPOH of the Society of Pediatric Oncology and Hematology.Data of 22 patients with NWRT and primary lung metastases were retrospectively reviewed. Analyses included epidemiology, tumor characteristics, chemotherapy, local treatment, and outcome.The following diagnoses were registered: Malignant Rhabdoid tumor of the kidney (MRTK, n=15), Renal-cell carcinoma (RCC, n=3), Clear-cell sarcoma of the kidney (CCSK, n=3), and primitive neuro ectodermal tumor (PNET, n=1). Median age of patients at diagnosis was 14 months. Overall survival was 36.36% (8/22). Of the 15 children with MRTK 3 survived, 3/3 patients with RCC, 1/3 patients with CCSK, and 1/1 patient with PNET survived. Lung metastases disappeared in 6 patients after initial chemotherapy, 6/8 patients undergoing local treatment of lung metastases (surgery, irradiation, or both) achieved complete remission. Only patients with complete clearance of lung lesions, either through neoadjuvant chemotherapy or subsequent local treatment, survived. Mean Follow up was 31 months (1-137).Survival of patients with stage IV NWRT is dismal. Complete removal of lung metastases seems mandatory for survival. An aggressive diagnostic and therapeutic approach seems justified in affected children.

[Tumor predisposition syndromes and nephroblastoma : Early diagnosis with imaging]. / Tumorprädispositionssyndrome und Nephroblastom : Frühe Diagnose mit Bildgebung.

CLINICAL/METHODICAL ISSUE: The Beckwith-Wiedemann spectrum (BWSp) as well as the WT1-related syndromes, Denys-Drash syndrome (DDS) and WAGR spectrum (Wilms tumor, Aniridia, genitourinary anomalies and a range of developmental delays) are tumor predisposition syndromes (TPS) of Wilms tumor (WT). Patients with associated TPS are at higher risk of developing chronic kidney disease and bilateral and metachronous tumors as well as nephrogenic rests. STANDARD RADIOLOGICAL METHODS: Standard imaging diagnostics for WT include renal ultrasound and magnetic resonance imaging (MRI). In the current renal tumor studies Umbrella SIOP-RTSG 2016 and Randomet 2017, thoracic computed tomography (CT) is also recommended as standard. Positron emission tomography (PET)-CT and whole-body MRI, on the other hand, are not part of routine diagnostics. METHODOLOGICAL INNOVATIONS: In recent publications, renal ultrasound is recommended every 3 months until the age of 7 years in cases of clinical suspicion or molecularly proven TPS. PERFORMANCE: Patients with TPS and regular renal ultrasounds have smaller tumor volumes and lower tumor stages at WT diagnosis than patients without such a screening. This allows a reduction of therapy intensity and facilitates the performance of nephron sparing surgery, which is prognostically relevant especially in bilateral WT. ACHIEVEMENTS: Early diagnosis of WT in the context of TPS ensures the greatest possible preservation of healthy and functional renal tissue. Standardized screening by regular renal ultrasounds should therefore be firmly established in clinical practice. PRACTICAL RECOMMENDATIONS: The initial diagnosis of TPS is clinical and requires a skilled and attentive examiner in the presence of sometimes subtle clinical manifestations, especially in the case of BWSp. Clinical diagnosis should be followed by genetic testing, which should then be followed by sonographic screening.

Monitoring, management, and outcome of hypotension in Intensive Care Unit patients, an international survey of the European Society of Intensive Care Medicine.

INTRODUCTION: Hypotension in the ICU is common, yet management is challenging and variable. Insight in management by ICU physicians and nurses may improve patient care and guide future hypotension treatment trials and guidelines. METHODS: We conducted an international survey among ICU personnel to provide insight in monitoring, management, and perceived consequences of hypotension. RESULTS: Out of 1464 respondents, 1197 (81.7%) were included (928 physicians (77.5%) and 269 nurses (22.5%)). The majority indicated that hypotension is underdiagnosed (55.4%) and largely preventable (58.8%). Nurses are primarily in charge of monitoring changes in blood pressure, physicians are in charge of hypotension treatment. Balanced crystalloids, dobutamine, norepinephrine, and Trendelenburg position were the most frequently reported fluid, inotrope, vasopressor, and positional maneuver used to treat hypotension. Reported complications believed to be related to hypotension were AKI and myocardial injury. Most ICUs do not have a specific hypotension treatment guideline or protocol (70.6%), but the majority would like to have one in the future (58.1%). CONCLUSIONS: Both physicians and nurses report that hypotension in ICU patients is underdiagnosed, preventable, and believe that hypotension influences morbidity. Hypotension management is generally not protocolized, but the majority of respondents would like to have a specific hypotension management protocol.

Evaluation of psychosocial distress in patients treated in a community-based oncology group practice in Germany.

BACKGROUND: Systematic evaluation of psychosocial distress in oncology outpatients is an important issue. We assessed feasibility and benefit of standardized routine screening using the Distress Thermometer (DT) and Problem List (PL) in all patients of our community-based hematooncology group practice. PATIENTS AND METHODS: One thousand four hundred forty-six patients were screened between July 2008 and September 2008. Five hundred randomly selected patients were sent a feedback form. RESULTS: The average distress level was 4.7, with 37% indicating a distress level >5. Patients with nonmalignant diseases (81% autoimmune diseases or hereditary hemochromatosis) showed the highest distress level of 5.2. Most distressed were patients who just learned about relapse or metastases (6.4), patients receiving best supportive care (5.4) and patients receiving adjuvant antihormonal therapy (5.4). Ninety-seven percent of patients appreciated to speak to their doctor about their distress. Fifty-six percent felt better than usual after this consultation. CONCLUSION: DT and PL are feasible instruments to measure distress in hematooncology outpatients receiving routine care. DT and PL are able to improve doctor-patient communication and thus should be implemented in routine patient care. The study shows that distress is distributed differently between individuals, disease groups and treatment phases.

Update on relapses in unilateral nephroblastoma registered in 3 consecutive SIOP/GPOH studies - a report from the GPOH-nephroblastoma study group.

INTRODUCTION: Treatment and stratification of progressive/relapsed unilateral nephroblastoma (PD) has significantly evolved over the last 20 years. Early PD (≤ 6 months), initial high risk histology, local stage III, multiple site PD and stage IV have been implemented as high risk classification factors and novel drugs have been introduced. PATIENTS AND METHODS: We analysed all 251 patients having had a unilateral nephroblastoma (Stage I-IV) and progressive disease who had been treated according to SIOP9/GPO (n = 77), SIOP93-1/GPOH (n = 93) and SIOP2001/GPOH (n = 81) initially. RESULTS: 3y-overall survival (OS) increased from 43% to 61% and 59% respectively (both p<0.01). 3y-OS for localized stage I-III rose from 43% to 65% and 68% respectively while only little improvement can be seen for initial stage IV patients with 43%, 53% and 44% respectively. Multivariate analysis confirmed high risk histology, local stage III, shorter time to PD, combined relapse as independent risk factors. 26 patients had received high-dose chemotherapy showing 64% 3y-OS compared to 54% for all non-transplanted (p=0.11). CONCLUSION: Structuring the treatment of progressive nephroblastoma as well as introducing new drugs have improved the outcome significantly. However improvement is depending on the specific risk profile. Very high risk tumours are often resistant to conventional treatment, hence an international uniform treatment concept is needed to achieve conclusive results in this small group.

Association of intraoperative hypotension with postoperative morbidity and mortality: systematic review and meta-analysis.

BACKGROUND: Intraoperative hypotension, with varying definitions in literature, may be associated with postoperative complications. The aim of this meta-analysis was to assess the association of intraoperative hypotension with postoperative morbidity and mortality. METHODS: MEDLINE, Embase and Cochrane databases were searched for studies published between January 1990 and August 2018. The primary endpoints were postoperative overall morbidity and mortality. Secondary endpoints were postoperative cardiac outcomes, acute kidney injury, stroke, delirium, surgical outcomes and combined outcomes. Subgroup analyses, sensitivity analyses and a meta-regression were performed to test the robustness of the results and to explore heterogeneity. RESULTS: The search identified 2931 studies, of which 29 were included in the meta-analysis, consisting of 130 862 patients. Intraoperative hypotension was associated with an increased risk of morbidity (odds ratio (OR) 2.08, 95 per cent confidence interval 1.56 to 2.77) and mortality (OR 1.94, 1.32 to 2.84). In the secondary analyses, intraoperative hypotension was associated with cardiac complications (OR 2.44, 1.52 to 3.93) and acute kidney injury (OR 2.69, 1.31 to 5.55). Overall heterogeneity was high, with an I2 value of 88 per cent. When hypotension severity, outcome severity and study population variables were added to the meta-regression, heterogeneity was reduced to 50 per cent. CONCLUSION: Intraoperative hypotension during non-cardiac surgery is associated with postoperative cardiac and renal morbidity, and mortality. A universally accepted standard definition of hypotension would facilitate further research into this topic.

Definition and incidence of hypotension in intensive care unit patients, an international survey of the European Society of Intensive Care Medicine.

INTRODUCTION: Although hypotension in ICU patients is associated with adverse outcome, currently used definitions are unknown and no universally accepted definition exists. METHODS: We conducted an international, peer-reviewed survey among ICU physicians and nurses to provide insight in currently used definitions, estimations of incidence, and duration of hypotension. RESULTS: Out of 1394 respondents (1055 physicians (76%) and 339 nurses (24%)), 1207 (82%) completed the questionnaire. In all patient categories, hypotension definitions were predominantly based on an absolute MAP of 65 mmHg, except for the neuro(trauma) category (75 mmHg, p < 0.001), without differences between answers from physicians and nurses. Hypotension incidence was estimated at 55%, and time per day spent in hypotension at 15%, both with nurses reporting higher percentages than physicians (estimated mean difference 5%, p = 0.01; and 4%, p < 0.001). CONCLUSIONS: An absolute MAP threshold of 65 mmHg is most frequently used to define hypotension in ICU patients. In neuro(trauma) patients a higher threshold was reported. The majority of ICU patients are estimated to endure hypotension during their ICU admission for a considerable amount of time, with nurses reporting a higher estimated incidence and time spent in hypotension than physicians.

Expanding ecological assessment by integrating microorganisms into routine freshwater biomonitoring.

Bioindication has become an indispensable part of water quality monitoring in most countries of the world, with the presence and abundance of bioindicator taxa, mostly multicellular eukaryotes, used for biotic indices. In contrast, microbes (bacteria, archaea and protists) are seldom used as bioindicators in routine assessments, although they have been recognized for their importance in environmental processes. Recently, the use of molecular methods has revealed unexpected diversity within known functional groups and novel metabolic pathways that are particularly important in energy and nutrient cycling. In various habitats, microbial communities respond to eutrophication, metals, and natural or anthropogenic organic pollutants through changes in diversity and function. In this review, we evaluated the common trends in these changes, documenting that they have value as bioindicators and can be used not only for monitoring but also for improving our understanding of the major processes in lotic and lentic environments. Current knowledge provides a solid foundation for exploiting microbial taxa, community structures and diversity, as well as functional genes, in novel monitoring programs. These microbial community measures can also be combined into biotic indices, improving the resolution of individual bioindicators. Here, we assess particular molecular approaches complemented by advanced bioinformatic analysis, as these are the most promising with respect to detailed bioindication value. We conclude that microbial community dynamics are a missing link important for our understanding of rapid changes in the structure and function of aquatic ecosystems, and should be addressed in the future environmental monitoring of freshwater ecosystems.

Maternal psychological distress and fetal growth trajectories: the Generation R Study.

BACKGROUND: Previous research suggests, though not consistently, that maternal psychological distress during pregnancy leads to adverse birth outcomes. We investigated whether maternal psychological distress affects fetal growth during the period of mid-pregnancy until birth. METHOD: Pregnant women (n=6313) reported levels of psychological distress using the Brief Symptom Inventory (anxious and depressive symptoms) and the Family Assessment Device (family stress) at 20.6 weeks pregnancy and had fetal ultrasound measurements in mid- and late pregnancy. Estimated fetal weight was calculated using head circumference, abdominal circumference and femur length. RESULTS: In mid-pregnancy, maternal distress was not linked to fetal size. In late pregnancy, however, anxious symptoms were related to fetal size after controlling for potential confounders. Anxious symptoms were also associated with a 37.73 g [95% confidence interval (CI) -69.22 to -6.25, p=0.019] lower birth weight. When we related maternal distress to fetal growth curves using multilevel models, more consistent results emerged. Maternal symptoms of anxiety or depression were associated with impaired fetal weight gain and impaired fetal head and abdominal growth. For example, depressive symptoms reduced fetal weight gain by 2.86 g (95% CI -4.48 to -1.23, p<0.001) per week. CONCLUSIONS: The study suggests that, starting in mid-pregnancy, fetal growth can be affected by different aspects of maternal distress. In particular, children of prenatally anxious mothers seem to display impaired fetal growth patterns during pregnancy. Future work should address the biological mechanisms underlying the association of maternal distress with fetal development and focus on the effects of reducing psychological distress in pregnancy.