A Historical Survey of Key Epidemiological Studies of Ionizing Radiation Exposure.

In this article we review the history of key epidemiological studies of populations exposed to ionizing radiation. We highlight historical and recent findings regarding radiation-associated risks for incidence and mortality of cancer and non-cancer outcomes with emphasis on study design and methods of exposure assessment and dose estimation along with brief consideration of sources of bias for a few of the more important studies. We examine the findings from the epidemiological studies of the Japanese atomic bomb survivors, persons exposed to radiation for diagnostic or therapeutic purposes, those exposed to environmental sources including Chornobyl and other reactor accidents, and occupationally exposed cohorts. We also summarize results of pooled studies. These summaries are necessarily brief, but we provide references to more detailed information. We discuss possible future directions of study, to include assessment of susceptible populations, and possible new populations, data sources, study designs and methods of analysis.

The benefit of active management in true knot of the umbilical cord: a retrospective study.

PURPOSE: To compare perinatal outcomes between active and routine management in true knot of the umbilical cord (TKUC). METHODS: A retrospective study of singletons born beyond 22 6/7 weeks with TKUC. Active management included weekly fetal heart rate monitoring(FHRM) ≥ 30 weeks and labor induction at 36-37 weeks. Outcomes in active and routine management were compared, including composite asphyxia-related adverse outcome, fetal death, labor induction, Cesarean section (CS) or Instrumental delivery due to non-reassuring fetal heart rate (NRFHR), Apgar5 score < 7, cord Ph < 7, neonatal intensive care unit (NICU) admission and more. RESULTS: The Active (n = 59) and Routine (n = 1091) Management groups demonstrated similar rates of composite asphyxia-related adverse outcome (16.9% vs 16.8%, p = 0.97). Active Management resulted in higher rates of labor induction < 37 weeks (22% vs 1.7%, p < 0.001), CS (37.3% vs 19.2%, p = 0.003) and NICU admissions (13.6% vs 3%, p < 0.001). Fetal death occurred exclusively in the Routine Management group (1.8% vs 0%, p = 0.6). CONCLUSION: Compared with routine management, weekly FHRM and labor induction between 36 and 37 weeks in TKUC do not appear to reduce neonatal asphyxia. In its current form, active management is associated with higher rates of CS, induced prematurity and NICU admissions. Labor induction before 37 weeks should be avoided.

Prevalence of Thyroid Nodules in Residents of Ukraine Exposed as Children or Adolescents to Iodine-131 from the Chornobyl Accident.

Background: Although childhood exposure to radioactive iodine-131 (I-131) is an established risk factor for thyroid cancer, evidence for an association with thyroid nodules is less clear. The objective of this study is to evaluate the association between childhood I-131 exposure and prevalence of ultrasound-detected thyroid nodules overall and by nodule histology/cytology (neoplastic/suspicious/non-neoplastic), size (<10 mm/≥10 mm), and number (single/multiple). Methods: This is a cross-sectional study of radiation dose (mean = 0.53 gray, range: 0.0003-31 gray) and screen-detected thyroid nodules conducted in 1998-2000 (median population age 21.5 years) in a cohort of 13,243 residents of Ukraine who were under 18 years at the time of the Chornobyl accident on April 26, 1986. Excess odds ratios per gray (excess odds ratio [EOR]/Gy) and confidence intervals (CIs) were estimated using logistic regression. Results: Among 13,078 eligible individuals, we identified 358 (2.7%) with at least one thyroid nodule. Significantly increased dose-response associations were found for all nodules and nodule groups with doses <5 Gy except individuals with non-neoplastic nodules. Among individuals with doses <5 Gy, the EOR/Gy for neoplastic nodules (5.35; CI: 2.19-15.5) was significantly higher than for non-neoplastic nodules (0.24; CI: 0.07-0.74), but the EOR/Gy did not vary by nodule size or number. Conclusions: Childhood exposure to I-131 is associated with an increased risk of thyroid nodules detected 12-14 years following exposure, and the risk for neoplastic nodules is higher than for non-neoplastic nodules. Analyses of incident thyroid nodules may help clarify dose-response patterns by nodule characteristics and provide insights into thyroid nodule etiology.

Radiation exposure and leukaemia risk among cohorts of persons exposed to low and moderate doses of external ionising radiation in childhood.

BACKGROUND: Many high-dose groups demonstrate increased leukaemia risks, with risk greatest following childhood exposure; risks at low/moderate doses are less clear. METHODS: We conducted a pooled analysis of the major radiation-associated leukaemias (acute myeloid leukaemia (AML) with/without the inclusion of myelodysplastic syndrome (MDS), chronic myeloid leukaemia (CML), acute lymphoblastic leukaemia (ALL)) in ten childhood-exposed groups, including Japanese atomic bomb survivors, four therapeutically irradiated and five diagnostically exposed cohorts, a mixture of incidence and mortality data. Relative/absolute risk Poisson regression models were fitted. RESULTS: Of 365 cases/deaths of leukaemias excluding chronic lymphocytic leukaemia, there were 272 AML/CML/ALL among 310,905 persons (7,641,362 person-years), with mean active bone marrow (ABM) dose of 0.11 Gy (range 0-5.95). We estimated significant (P < 0.005) linear excess relative risks/Gy (ERR/Gy) for: AML (n = 140) = 1.48 (95% CI 0.59-2.85), CML (n = 61) = 1.77 (95% CI 0.38-4.50), and ALL (n = 71) = 6.65 (95% CI 2.79-14.83). There is upward curvature in the dose response for ALL and AML over the full dose range, although at lower doses (<0.5 Gy) curvature for ALL is downwards. DISCUSSION: We found increased ERR/Gy for all major types of radiation-associated leukaemia after childhood exposure to ABM doses that were predominantly (for 99%) <1 Gy, and consistent with our prior analysis focusing on <100 mGy.

The Effect of Prostate-Specific Antigen (PSA) Test on Radiation Risk Estimate for Prostate Cancer Incidence among Atomic-Bomb Survivors.

Following our previous report on the radiation dose-response for prostate cancer incidence rates in the Life Span Study (LSS) cohort of atomic bomb survivors, we reevaluated the radiation-related risk adjusting for differences in baseline cancer incidence rates among three subsets of the LSS cohort defined by the timing of their first participation in biennial health examinations offered to the Adult Health Study (AHS) sub-cohort members and prostate-specific-antigen (PSA) testing status for AHS participants: 1. non-AHS participants, 2. AHS participants before receiving PSA test, and 3. AHS participants after receiving PSA test. We found a 2.9-fold increase in the baseline incidence rates among AHS participants after receiving PSA test. After adjusting for the PSA-testing-status effects on the baseline rates the estimated excess relative risk (ERR) per Gy was 0.54 (95% CI: 0.15, 1.05), which was almost identical to the previously reported unadjusted ERR estimate (0.57, 95% CI: 0.21, 1.00). The current results confirmed that, while the PSA testing among AHS participants increased the baseline incidence rates, it did not impact the radiation risk estimate, strengthening the previously reported dose-response relationship for prostate cancer incidence in the LSS. As the use of PSA tests continue in screening and medical settings, analyses of possible effects of PSA testing should be an important aspect of future epidemiological studies of the association between radiation exposure and prostate cancer.

Effect of radiation exposure on survival after first solid cancer diagnosis in A-bomb survivors.

BACKGROUND: Comparison of the estimated effect of atomic bomb radiation exposure on solid cancer incidence and solid cancer mortality in the RERF Life Span Study (LSS) reveals a difference in the magnitude and shape of the excess relative risk dose response. A possible contributing factor to this difference is pre-diagnosis radiation effect on post-diagnosis survival. Pre-diagnosis radiation exposure theoretically could influence post-diagnosis survival by affecting the genetic makeup and possibly aggressiveness of cancer, or by compromising tolerance for aggressive treatment for cancer. METHODS: We analyze the radiation effect on post-diagnosis survival in 20,463 LSS subjects diagnosed with first-primary solid cancer between 1958 and 2009 with particular attention to whether death was caused by the first-primary cancer, other cancer, or non-cancer diseases. RESULTS: From multivariable Cox regression analysis of cause-specific survival, the excess hazard at 1 Gy (EH1Gy) for death from the first primary cancer was not significantly different from zero - p = 0.23, EH1Gy = 0.038 (95 % CI: -0.023, 0.104). Death from other cancer and death from non-cancer diseases both were significantly associated with radiation dose: other cancer EH1Gy = 0.38 (95 % CI: 0.24, 0.53); non-cancer EH1Gy = 0.24 (95 % CI: 0.13, 0.36), both p < 0.001. CONCLUSION: There is no detectable large effect of pre-diagnosis radiation exposure on post-diagnosis death from the first primary cancer in A-bomb survivors. IMPACT: A direct effect of pre-diagnosis radiation exposure on cancer prognosis is ruled out as an explanation for the difference in incidence and mortality dose response in A-bomb survivors.

Role of Gynecological Ultrasound in Evaluation of Pelvic Urologic Pathologies.

BACKGROUND: Advances in examination techniques have improved routine assessment of non-gynecological structures in the pelvis. OBJECTIVES: To describe the sonographic features of incidental urological abnormalities found during gynecological transvaginal ultrasound. METHODS: A retrospective descriptive analysis of patients who underwent gynecological ultrasound and were diagnosed with urologic findings was performed. The sonographic features of the findings including size, echogenicity, and vascularity were examined. RESULTS: Gynecological ultrasound diagnosed urological findings in nine women. Two had primary neoplasms of the urinary bladder, one had metastases to the urinary bladder, one had polyps in the distal ureters, four presented with calculus in the distal ureters (one of them was 19 weeks pregnant), and one showed diverticulum of the urethra. At presentation five women (56%) had urinary complaints. Two patients (22%) with abdominal pain with distal ureteral calculi had normal transabdominal ultrasound targeted to the urinary system prior to the gynecological sonography. CONCLUSIONS: Transvaginal ultrasound is useful in the diagnosis of urological abnormalities, mainly in the urinary bladder and the distal ureters. We suggest adding transvaginal assessment for female patients with urinary complains in whom transabdominal ultrasound of urinary system was unremarkable.

Risk factors for bladder injury during placenta accreta spectrum surgery.

OBJECTIVES: To identify risk factors associated with bladder injury during placenta accreta spectrum (PAS) surgeries. METHODS: This retrospective cohort study was conducted at the Chaim Sheba Medical Center. The study population included pregnant women diagnosed with PAS undergoing uterine-preserving surgery or hysterectomy. Women with and without operative bladder injury were compared by univariate analysis followed by multivariate analysis. A sub-analysis of women without preoperative sonographic suspicion of bladder invasion was performed. RESULTS: A total of 312 women were included in the study. Bladder injury incidence was 9.3% (n = 29). Uterine preservation was performed in 267/312 (85.6%) women. The number of previous cesarean deliveries and a preoperative sonogram suspicious for placenta percreta were found to be independent risk factors for intraoperative bladder injury (odds ratio [OR] 1.30, P = 0.019, and OR 5.23, P = 0.002, respectively). The number of previous cesarean deliveries and preoperative sonographic suspicion of placenta percreta were also associated with bladder injury in the sub-analysis (OR 1.30, P = 0.044 for previous cesarean deliveries, and OR 3.36, P = 0.036, for preoperative suspicion of bladder injury). CONCLUSION: The number of previous cesarean deliveries and preoperative suspicion of placenta percreta are preoperative factors that can assist in preoperative planning and intraoperative management of PAS cases.

Pooled Analysis of Meningioma Risk Following Treatment for Childhood Cancer.

Importance: Meningioma is the most common subsequent neoplasm following cranial irradiation among survivors of childhood cancer, but there are still uncertainties regarding the magnitude of the radiation dose-response association, potential modifiers of radiation risks, and the role of chemotherapy. Objective: To evaluate meningioma risk in survivors of childhood cancer following radiotherapy and chemotherapy and identify possible modifying factors of radiation-associated risk. Design, Setting, and Participants: This international case-control study pooled data from 4 nested case-control studies of survivors of childhood cancer diagnosed between 1942 and 2000, followed through 2016. Cases were defined as participants diagnosed with a subsequent meningioma. Controls were matched to cases based on sex, age at first cancer diagnosis, and duration of follow-up. Data were analyzed from July 2019 to June 2022. Exposures: Radiation dose (Gy) to the meningioma site and cumulative chemotherapy doses, including intrathecal and systemic methotrexate doses. Main Outcomes and Measures: The main outcome was subsequent meningioma, assessed using odds ratios (ORs) and excess odds ratios per gray (EOR/Gy). Results: The analysis included 273 survivors of childhood cancer who developed meningioma (cases) and 738 survivors who did not (controls), with a total of 1011 individuals (median [IQR] age at first cancer diagnosis 5.0 [3.0-9.2] years; 599 [59.2%] female). Median (IQR) time since first cancer was 21.5 (15.0-27.0) years. Increasing radiation dose was associated with increased risk of meningioma (EOR/Gy, 1.44; 95% CI, 0.62-3.61), and there was no evidence of departure from linearity (P = .90). Compared with survivors who were not exposed to radiation therapy, those who received doses of 24 Gy or more had more than 30-fold higher odds of meningioma (OR, 33.66; 95% CI, 14.10-80.31). The radiation dose-response association was significantly lower among patients treated at age 10 years or older compared with those treated before age 10 years (EOR/Gy, 0.57; 95% CI, 0.18-1.91 vs 2.20; 95% CI, 0.87-6.31; P for heterogeneity = .03). Risk associated with radiation remained significantly elevated 30 years after exposure (EOR/Gy, 3.76; 95% CI, 0.77-29.15). We found an increased risk of meningioma among children who had received methotrexate (OR, 3.43; 95% CI, 1.56-7.57), but no evidence of a dose-response association or interaction with radiation dose. Conclusions and Relevance: These findings suggest that the meninges are highly radiosensitive, especially for children treated before age 10 years. These results support the reduction in whole-brain irradiation over recent decades and the prioritization of approaches that limit radiation exposure in healthy tissue for children. The persistence of elevated risks of meningiomas for 30 years after cranial radiotherapy could help inform surveillance guidelines.

Delivery Outcome of Fetuses with Congenital Heart Disease-Is It Influenced by Prenatal Diagnosis?

Objective: The objective of this study is to assess the delivery outcomes of neonates with congenital heart defects (CHD), and to explore the effect of prenatal diagnosis on these outcomes. Methods: A retrospective study including singleton deliveries between 2011 and 2020. All singleton neonates delivered at >24 weeks of gestation were included in this study. Fetuses with known prenatal anomalies other than CHD were excluded from this study. Pregnancy and neonatal outcomes were analyzed. A comparison was made between pregnancies with CHD and controls; and between pregnancies with prenatal diagnosis of CHD and postnatal diagnosis of CHD. Results: A total of 1598 neonates with CHD (688, 43.1% diagnosed prenatally) comprised the study group, compared to 85,576 singleton controls. Pregnancies with CHD had significantly increased BMI before pregnancy, suffered more from diabetes and chronic hypertension, had more inductions of labor, and had more cesarean deliveries (CD) including both elective CD and urgent CD due to non-reassuring fetal monitor (NRFHR) (OR = 1.75; 95%CI 1.45−2.14). Prenatal diagnosis of CHD is associated with a significant increased rate of induction of labor compared to postnatal diagnosis of CHD (OR = 1.59; 95% CI 1.15−2.22), but did not affect the mode of delivery including the rate of CD and CD due to non-reassuring fetal heart rate (NRFHR). Gestational age at birth and birthweight were significantly lower in pregnancies with CHD compared to controls, with no difference between prenatal to postnatal diagnosis of the anomaly. Neonates with CHD had a higher incidence of hypoxic ischemic encephalopathy and seizures compared to controls without any impact by prenatal diagnosis. Conclusion: Prenatal diagnosis of CHD is associated with an increased rate of induction of labor, with no increased rate of CD and CD due to NRFHR. The 5-min Apgar score is lower in pregnancies with postnatal diagnosis of CHD.

Age effects on radiation response: summary of a recent symposium and future perspectives.

One of the principal uncertainties when estimating population risk of late effects from epidemiological data is that few radiation-exposed cohorts have been followed up to extinction. Therefore, the relative risk model has often been used to estimate radiation-associated risk and to extrapolate risk to the end of life. Epidemiological studies provide evidence that children are generally at higher risk of cancer induction than adults for a given radiation dose. However, the strength of evidence varies by cancer site and questions remain about site-specific age at exposure patterns. For solid cancers, there is a large body of evidence that excess relative risk (ERR) diminishes with increasing age at exposure. This pattern of risk is observed in the Life Span Study (LSS) as well as in other radiation-exposed populations for overall solid cancer incidence and mortality and for most site-specific solid cancers. However, there are some disparities by endpoint in the degree of variation of ERR with exposure age, with some sites (e.g., colon, lung) in the LSS incidence data showing no variation, or even increasing ERR with increasing age at exposure. The pattern of variation of excess absolute risk (EAR) with age at exposure is often similar, with EAR for solid cancers or solid cancer mortality decreasing with increasing age at exposure in the LSS. We shall review the human data from the Japanese LSS cohort, and a variety of other epidemiological data sets, including a review of types of medical diagnostic exposures, also some radiobiological animal data, all bearing on the issue of variations of radiation late-effects risk with age at exposure and with attained age. The paper includes a summary of several oral presentations given in a Symposium on "Age effects on radiation response" as part of the 67th Annual Meeting of the Radiation Research Society, held virtually on 3-6 October 2021.

Impact of uncertainties in exposure assessment on thyroid cancer risk among cleanup workers in Ukraine exposed due to the Chornobyl accident.

A large excess risk of thyroid cancer was observed among Belarusian/Russian/Baltic Chornobyl cleanup workers. A more recent study of Ukraine cleanup workers found more modest excess risks of thyroid cancer. Dose errors in this data are substantial, associated with model uncertainties and questionnaire response. Regression calibration is often used for dose-error adjustment, but may not adequately account for the full error distribution. We aimed to examine the impact of exposure-assessment uncertainties on thyroid cancer among Ukrainian cleanup workers using Monte Carlo maximum likelihood, and compare with results derived using regression calibration. Analyses assessed the sensitivity of results to various components of internal and external dose. Regression calibration yielded an excess odds ratio per Gy (EOR/Gy) of 0.437 (95% CI - 0.042, 1.577, p = 0.100), compared with the EOR/Gy using Monte Carlo maximum likelihood of 0.517 (95% CI - 0.039, 2.035, p = 0.093). Trend risk estimates for follicular morphology tumors exhibited much more extreme effects of full-likelihood adjustment, the EOR/Gy using regression calibration of 3.224 (95% CI - 0.082, 30.615, p = 0.068) becoming ~ 50% larger, 4.708 (95% CI - 0.075, 85.143, p = 0.066) when using Monte Carlo maximum likelihood. Results were sensitive to omission of external components of dose. In summary, use of Monte Carlo maximum likelihood adjustment for dose error led to increases in trend risks, particularly for follicular morphology thyroid cancers, where risks increased by ~ 50%, and were borderline significant. The unexpected finding for follicular tumors needs to be replicated in other exposed groups.

A retrospective clinical analysis of 20 cases of congenital lung masses.

BACKGROUND: Congenital-pulmonary-airway-malformation (CPAM) and bronchopulmonary-sequestration (BPS) are rare conditions. The objective of this study was to describe the sonographic characteristics and prenatal course of fetal lung mass. METHODS: A retrospective study on 20 pregnancies with CPAM and BPS diagnosed during 2018-2018 was performed. Data evaluated included gestational age (GA) at diagnosis, size of lesion, CPAM-volume-ratio (CVR), associated sonographic findings and pregnancy outcome. RESULTS: Fourteen cases of CPAM and six cases of BPS were evaluated. The average GA at diagnosis was 22 weeks'-gestation (range 17-26). 66% were macrocystic-multicystic. Five cases of BPS (71.4%) had other structural anomalies. None of the fetuses with CPAM had additional anomalies. Four pregnancies (20%) underwent termination due to severe hydrops fetalis. Two cases of CPAM (15%) had spontaneous resolution by 30 week's-gestation; three cases (20%) continued to grow during pregnancy and all the rest reached their largest size at 25-28 week's-gestation. Most cases delivered at term (average 37.6 range 32.2-41.4). Two children had lobectomy at 11 and 12 months of life. CONCLUSIONS: Careful follow-up during pregnancy may result in term delivery of adequate-for-gestational-age newborns, with no need for admission to the NICU, with only 10% need for lobectomy during the first year of life.

Antenatal Detection of True Knot in the Umbilical Cord - How Accurate Can We Be?

BACKGROUND: Umbilical cord knot (UCK) is associated with increased risk of fetal death, but is usually diagnosed only after delivery. Our objective was to examine the accuracy of prenatal ultrasound in the diagnosis of UCK and the outcomes of these pregnancies. METHODS: A prospective study was performed on 56 patients in which UCK was suspected during a routine level-II anatomical scan (study group). Data included demographics, pregnancy outcome, and short-term neonatal follow-up. The control group included pregnant women with normal pregnancy without UCK in a 4:1 ratio matched for gestational age at delivery. RESULTS: True knot was observed postnatally in 54 out of 56 fetuses (detection rate of 96.4 %). Gestational age at diagnosis of UCK was 22.1 ±â€Š3.1 weeks. The female to male ratio was 1:1 in both groups. Maternal age and parity were significantly higher in pregnancies with UCK compared to controls. The mean gestational age at delivery was 37.1 weeks of gestation in the UCK group. There was no difference in the birthweight percentile. 47 patients (87 %) underwent induction of labor. There were no differences in the rate of cesarean section or Apgar scores. No neonate with UCK needed ventilation. None suffered from seizures and none needed brain imaging. There were no cases of fetal or neonatal death in the pregnancies with UCK. CONCLUSION: There is a high detection rate of UCK during targeted scan of the umbilical cord performed during the level-II anatomical scan. Careful pregnancy follow-up and early term delivery may result in excellent obstetrical outcomes.

Prenatal diagnosis of major aortopulmonary collateral arteries (MAPCA) in fetuses with pulmonary atresia with ventricular septal defect and agenesis of ductus arteriosus.

OBJECTIVE: The aim of this study was to describe the prenatal diagnosis of Major Aortopulmonary Collateral Arteries (MAPCAs), and to present a systematic ultrasound method for evaluating lung vascularity in fetuses with pulmonary atresia with ventricular septal defect (PAVSD) and agenesis of ductus arteriosus (DA). METHOD: This retrospective study evaluated fetuses diagnosed with PAVSD with agenesis of DA, for the presence of the MAPCAs anomaly. Fetal pulmonary vasculature was investigated by 2D and 4D Spatio Temporal Image Correlation (STIC) technology using High Definition Color Doppler. RESULTS: Over a 10 year period, six fetuses were diagnosed with MAPCAs. Prenatal diagnosis was made between 17 w 6 d and 28 w 4 d in five fetuses, with the sixth diagnosed at 37 w 6 d. All six had PAVSD with agenesis DA, four exhibited pulmonic atresia without any arterial outflow, while two fetuses presented with absent left pulmonary artery, and a miniscule right pulmonary artery. In five cases, the parents elected to terminate the pregnancy and the last, although born alive, did not survive an attempt at restorative surgery and died at the age of 5 months. Postnatal CT angiography imaging of this case revealed the subclavian origin of the MAPCAs. Chromosomal micro array analysis of the amniotic fluid revealed that five of the six fetuses were normal and one was lost to follow up. CONCLUSION: MAPCAs should be investigated in cases of PAVSD with agenesis DA. A meticulous ultrasound evaluation using 2D and 4D STIC can permit the prenatal diagnosis of this anomaly and provide the parents with the opportunity for prenatal consultation.

Intra-observer variability of Doppler measurements in umbilical artery (UA) and middle cerebral artery (MCA) in uncomplicated term pregnancies.

OBJECTIVE: To evaluate the intra-observer variability of the middle cerebral artery (MCA) and umbilical artery (UA) Doppler measurement taken under optimal conditions in term, uncomplicated pregnancies. METHODS: A prospective study on uncomplicated singleton term pregnancies was performed. Multiple Doppler measurements were taken in the MCA and the UA by one examiner. Intra-rater agreement was calculated. Doppler indices were correlated to fetal biometric parameters and to gestational age. RESULTS: One hundred patients were recruited. MCA indices were found to have the highest strength of intra-rater/observer agreement (K = 0.888) versus only a "good" agreement for UA pulsatility index (PI) (K = 0.755).The MCA-PI was significantly correlated with BPD (r = -0.198, p = .047), EFW (r = -0.241, p = .01) and birthweight (r = -0.208, p = .03). A statistically significant decrease was found in the MCA PI (r = -.422, p < .001) and in the CPR (r = -0.444, p < .001) with advancing pregnancy, between 37 and 42 weeks gestation. The UA PI did not change significantly (p = .099) during this period. CONCLUSIONS: MCA PI measured at term is reproducible with a high ICC. MCA PI significantly decreases with advancing gestation at term. No correlation was found between Doppler measurements and time to delivery.

The perils of true knot of the umbilical cord: antepartum, intrapartum and postpartum complications and clinical implications.

BACKGROUND: True knot of the umbilical cord (TKUC) is found in 0.3-2.1% of pregnancies and is associated with an increased risk of adverse perinatal outcomes. METHODS: A retrospective cohort study including all singleton pregnancies delivered from 2011 to 2019 was performed. Diagnosis of TKUC was made postnatally, immediately after delivery of the baby. Comparison was made between pregnancies with and without TKUC regarding maternal, fetal and neonatal adverse outcome. RESULTS: Overall, 867/85,541 (1%) pregnancies were diagnosed with TKUC. Maternal age, BMI, gravidity and parity were significantly higher in pregnancies with TKUC as well as higher rate of induction of labor, meconium-stained amniotic fluid, and delivery prior to 37 weeks. The rate of cesarean deliveries due to non-reassuring-fetal monitor was significantly higher in pregnancies with TKUC. Overall, there were 2.5% IUFD in pregnancies with TKUC vs. 1% in pregnancies without TKUC (p < 0.001). Importantly, the rate of IUFD prior to 37 weeks of gestation was not significantly higher in the group with TKUC, however, the rate of IUFD after 37 weeks of gestation was 10 folds higher in fetuses with TKUC, 0.9% vs. 0.08% (p < 0.001). Significantly, more neonates with TKUC needed phototherapy or suffered from hypoglycemia. There were no differences in the 5 min Apgar scores, admission to the NICU and number of days of hospitalization. CONCLUSION: Pregnancies complicated with TKUC are associated with a tenfold higher risk of IUFD beyond 37 weeks of gestation. To the results of this study suggest that it would be prudent to induce labor around 37 weeks of gestation in pregnancies with prenatal diagnosis of TKUC. It may be warranted to use continuous fetal monitoring during labor and delivery in those cases were antenatal diagnosis of TKUC is made.

Incidental finding of meconium-stained amniotic fluid in elective cesarean deliveries: Features and perils.

OBJECTIVE: To characterize pregnancies in which meconium-stained amniotic fluid (MSAF) was incidentally discovered during elective caesarean delivery (CD), and to evaluate the association with adverse neonatal outcomes. METHODS: A retrospective study was performed on all patients who underwent elective CD with singleton pregnancies between March 2011 and June 2020. Data analyzed included maternal, pregnancy, and neonatal characteristics. A comparison was made between pregnancies with clear amniotic fluid, MSAF, and thick MSAF. RESULTS: During the study period, 10 445 patients with singleton pregnancies underwent elective CD. Of them, 368 (3.5%) had MSAF and 31 (0.3%) had thick MSAF. Patients with MSAF gained more weight during pregnancy and suffered more from diabetes compared with patients with clear fluid. Significantly more pregnancies with MSAF had either oligohydramnios or polyhydramnios. Pregnancies in the thick-MSAF group had more intrahepatic cholestasis of pregnancy. No differences were found between the groups in the composite adverse neonatal outcome, including 5-min Apgar score, need for mechanical ventilation, and admission to the neonatal intensive care unit. CONCLUSION: The incidental finding of MSAF during elective CD is not associated with increased risks of adverse neonatal outcomes.

Long-term follow-up of congenital anomalies of the kidney and urinary tract diagnosed in utero: a longitudinal study.

BACKGROUND: Congenital-anomalies of the kidney-and-urinary-tract (CAKUT) are diagnosed in 3-6 per 1000 live-births. The objective of the current study was to examine the short and long-term outcomes of children diagnosed prenatally with CAKUT. METHODS: A retrospective study was performed in 2018 on all pregnancies diagnosed with CAKUT between 2004 and 2008 at our hospital. Pregnancy outcomes and long-term morbidity were evaluated. Comparison was made between mild and severe forms of CAKUT and between unilateral and bilateral anomalies. RESULTS: Ninety-eight children were included in the study. Most of them were born with an adequate weight for gestational-age, and were born at term by vaginal-deliveries. Children with major renal anomalies suffered significantly more frequently from recurrent UTIs (33.3% vs. 8.4%), needed more preventive antibiotics (50% vs. 20.5%), and had more renal surgeries (75% vs. 28%) than those with milder forms of CAKUT. Significantly more children with polycystic/multicystic kidney disease had recurrent UTIs (50% compared to 25% of the children with renal agenesis, and 5.6% of the children with hydronephrosis/hydroureter). There were no significant differences in the need for neurodevelopmental follow-up between the different groups of severity. Unilateral CAKUT patients required longer periods of nephrologist follow-up and repeated sonographic exams compared to bilateral CAKUT patients. Children with bilateral CAKUT more often needed special educational support than peers with unilateral disease (29.4% vs. 11.1%, P = 0.03). CONCLUSIONS: Pregnancies whose children are diagnosed with CAKUT in utero usually deliver at term, with adequate-weight for gestational-age. The most common long-term comorbidities in children were recurrent UTIs and the use of preventive antibiotics was often needed. Expecting couples can be reassured of a generally good outcome of their children, at least during the first decade of life.