The first three years: The association of early postpartum depressive symptoms with infant and toddler development.

BACKGROUND: The influence of postpartum depression (PPD) on child development has been a source of professional interest and practical relevance. OBJECTIVE: This study investigated the association of early PPD symptoms with developmental domains. DESIGN AND METHOD: This historical cohort study included 574,282 children attending Mother Child Healthcare Centers in Israel from January 1, 2014 to July 31, 2020, who underwent at least one developmental screening examination by public health nurses up to age 36 months, and whose mothers completed the Edinburgh Postnatal Depression Scale (EPDS) postnatally. Developmental milestone tasks included four domains: fine and gross motor, language/communication, and social/behavioral. RESULTS: The rate of failure to complete age-appropriate tasks was higher among children whose mothers had scored ≥ 10 on the EPDS on the majority of tasks in every domain. DISCUSSION: This large population-based study has demonstrated the association between early maternal postnatal depressive symptoms and failure to meet developmental milestones across domains, until three years. Recommendations for practice focus on the mother, the child, and health policy.

Neonatal morbidities and postnatal growth failure in very low birth weight, very preterm infants.

AIM: To assess postnatal growth in infants with and without major neonatal morbidities. METHODS: This study is based on analysis of data collected by the Israel Neonatal Network on VLBW infants (≤1500 g) born in Israel from 2009 to 2018. Postnatal growth was assessed in two 5 years epochs: 2009-2013 (n = 4583) and 2014-2018 (n = 4558). Outcome was considered as severe, mild and no postnatal growth failure (PNGF). Morbidities included respiratory distress syndrome, bronchopulmonary dysplasia, necrotising enterocolitis, patent ductus arteriosus and grades 3-4 intraventricular haemorrhage. Multinomial logistic regression analyses with the generalised estimating equation approach were applied. RESULTS: The study population composed 9141 infants. Of them, 2089 had at least one major morbidity and 7052 infants had none. In infants with no morbidities, 2.1% had severe PNGF, 23.7% mild PNGF and 74.2% had no PNGF, as compared to 13.6%, 43.9% and 42.5%, respectively, in infants with any major neonatal morbidity (p < 0.0001). CONCLUSION: Despite enormous advances in neonatal care, postnatal growth remains a challenge in VLBW infants, particularly in infants with major neonatal morbidities. Along with efforts to decrease morbidity, a more personalised plan and follow-up may be required in infants with major morbidities, given their high risk for diminished growth and potentially, adverse neurodevelopmental outcomes.

Preterm Singleton Birth Rate during the COVID-19 Lockdown: A Population-Based Study.

OBJECTIVE: The aim of the study is to evaluate the effect of the coronavirus disease 2019 (COVID-19) pandemic national lockdown period on the rate of singleton preterm births in Israel. STUDY DESIGN: This is a population-based cohort study of 3,41,291 singleton infants born in the months of January to July 2017 to 2020. Multivariable logistic regression analyses were used to estimate the influence of period and year on the rates of preterm births during the lockdown period (11th March - 5th May 2020) compared with rates before (January 1st 2020 - March 10th 2020), and after the lockdown (May 6th 2020-June 30th 2020) and to the corresponding periods in 2017to 2019. RESULTS: During the lockdown period the preterm birth rate (primary outcome) decreased by 9.7% from 5.05 to 4.56% in the pre-lockdown period (p = 0.006), an adjusted decrease of -0.52% (95% confidence interval -0.89%; -0.15%), odds ratio 0.898 (95% confidence interval 0.832; 0.970). CONCLUSION: The rate of singleton preterm births declined by 9.7% during the COVID-19 pandemic national lockdown period in Israel. KEY POINTS: · A 10% decline in all preterm deliveries was observed during the COVID-19 pandemic national lock-down period.. · The lock-down might influence environmental changes which contribute to the decrease in preterm deliveries.. · Changes in lifestyle, and societal behavior might contribute to the decrease in preterm deliveries..

Subfertility, use of fertility treatments and BRCA mutation status and the risk of ovarian cancer.

PURPOSE: The objective of the study is to evaluate the possible association between history of subfertility, fertility treatments, BRCA mutations and the risk of ovarian cancer. METHODS: This Israeli National Case-Control study included 1269 consecutive ovarian cancer cases and 2111 individually matched healthy controls. All participants were interviewed and molecular analysis of BRCA mutations were performed to 896 cases. The main outcome measure was reported history of subfertility and exposure to fertility treatments. RESULTS: The rate of reported subfertility was 15.1% and 14.3% in ovarian cancer cases and controls, respectively. However, subfertility was more prevalent in cases with borderline ovarian cancer (but not for invasive ovarian cancer cases) than controls. Multivariate conditional logistic regression revealed that the risk of borderline ovarian cancer was elevated in both women treated for subfertility and those that were not treated for subfertility, (OR = 1.74; 95% CI 0.9-3.36 and OR = 1.79; 95% CI 0.98-3.26, respectively). In non-carriers of BRCA1/2 mutations, fertility treatments were associated with a decreased risk of invasive ovarian cancer while a significant increased risk of borderline ovarian cancer was observed (OR = 2.92, 95%CI 1.67-5.10). CONCLUSIONS: Reported subfertility and exposure to fertility treatments were associated with borderline but not with invasive ovarian tumors. This association was more prominent in women who are non-carriers of a BRCA mutation.

Missed initial appointments at Israeli child development centres: Rate, reasons, and associated characteristics.

INTRODUCTION: Missed appointments (MAs) at child development centres (ChDCs) cause multiple problems: they preclude timely diagnosis and treatment of both the invited child and children whose appointment was delayed due to overbooking, as well as disrupting efficient organisational management. The aim of this study was to assess the rate and describe the reasons for missed appointments at Israeli ChDCs, and to evaluate the association of socio-demographic, clinical, and administrative variables with MA rates. METHODS: This nested case-control study included all children scheduled for initial appointments (N = 1143) at three centres during 1 year. Parents of children who missed their appointment and a sample of those who attended were interviewed by telephone. RESULTS: The rate of missed appointments was 26.6%, and the most frequent reasons were unexpected events (26.0%) and lack of insurance coverage (23.4%). Variables associated with lower MA rates were: having had ≥3 types of rehabilitative interventions (odds ratios (OR) = 0.26; 95% confidence interval [CI] 0.16-0.44), detailed referral letter (OR = 0.48; 95%CI 0.30-0.75), telephone reminder (OR = 0.37; 95%CI 0.24-0.57) and health maintenance organisations or private insurance coverage (OR = 0.12; 95%CI 0.06-0.17 and OR = 0.56; 95% CI 0.38-0.89, respectively). CONCLUSION: Encouraging physician's referral letters and personal-contact reminders can reduce missed appointments. Understanding the family's and the child's personal characteristics, and the organisational/administrative aspects of missed appointments may guide efforts to ensure timely care for every child.

Antenatal corticosteroid therapy is associated with a lower risk of cystic periventricular leukomalacia.

AIM: To evaluate the association of antenatal corticosteroids (ACS) therapy on the risk for cystic periventricular leukomalacia (c-PVL) in very low birth weight (VLBW), very preterm infants, whilst accounting for the occurrence of major neonatal morbidities; sepsis, necrotising enterocolitis, intraventricular haemorrhage and bronchopulmonary dysplasia. METHODS: Population-based observational cohort study applying data collected by the Israel national VLBW infant database from 1995-2016. RESULTS: Cystic PVL was diagnosed in 692 (6.8%) of the 10,170 study infants. Among 7522 infants exposed to ACS, the rate of c-PVL was 5.4%, compared to 10.7% among those not exposed (p < 0.0001). ACS was associated with significantly lower odds for c-PVL (Odds Ratio [OR] 0.69, 95% confidence interval [CI] 0.57-0.84). In subgroup analyses, excluding infants with one or more morbidities the rates of c-PVL ranged from 2.7% to 5.4% among infants exposed to ACS compared to 5.6% to 10.7% in those not exposed (all p < 0.0001). ACS was associated with significantly lower OR's for c-PVL in all subgroups, ranging from 0.52 (95% CI 0.40-0.66) to 0.62 (95% CI 0.50-0.77). CONCLUSION: Infants exposed to ACS had a significantly lower risk of c-PVL. Subgroup analyses excluding infants with major neonatal comorbidities showed a consistent reduction of 40%-50% in the risk for c-PVL following ACS therapy.

Antepartum Hemorrhage and Outcome of Very Low Birth Weight, Very Preterm Infants: A Population-Based Study.

OBJECTIVE: We aimed to determine the independent effect of maternal antepartum hemorrhage (APH) on mortality and major neonatal morbidities among very low birth weight (VLBW), very preterm infants. STUDY DESIGN: A population-based cohort study of VLBW singleton infants born at 24 to 31 weeks of gestation between 1995 and 2016 was performed. Infants born with the following pregnancy associated complications were excluded: maternal hypertensive disorders, prolonged rupture of membranes, amnionitis, maternal diabetes, and small for gestational age. APH included hemorrhage due to either placenta previa or placental abruption. Univariate and multivariable logistic regression analyses were performed to assess the effect of maternal APH on mortality and major neonatal morbidities. RESULTS: The initial cohort included 33,627 VLBW infants. Following exclusions, the final study population comprised 6,235 infants of whom 2,006 (32.2%) were born following APH and 4,229 (67.8%) without APH. In the APH versus no APH group, there were higher rates of extreme prematurity (24-27 weeks of gestation; 51.6% vs. 45.3%, p < 0.0001), mortality (20.2 vs. 18.5%, p = 0.011), bronchopulmonary dysplasia (BPD, 16.1 vs. 13.0%, p = 0.004) and death or adverse neurologic outcome (37.4 vs. 34.5%, p = 0.03). In the multivariable analyses, APH was associated with significantly increased odds ratio (OR) for BPD in the extremely preterm infants (OR: 1.31, 95% confidence interval: 1.05-1.65). The OR's for mortality, adverse neurological outcomes, and death or adverse neurological outcome were not significantly increased in the APH group. CONCLUSION: Among singleton, very preterm VLBW infants, maternal APH was associated with increased odds for BPD only in extremely premature infants, but was not associated with excess mortality or adverse neonatal neurological outcomes. KEY POINTS: · Outcome of very low birth weight infants born after antepartum hemorrhage (APH) was assessed.. · APH was not associated with higher infant mortality.. · APH was not associated with adverse neurological outcome.. · APH was associated with increased bronchopulmonary dysplasia in extremely preterm infants..

Cancer in IVF patients treated at age 40 years and older: long term follow-up.

RESEARCH QUESTION: Current knowledge of cancer risk among women who undergo IVF is based mainly on studies of women treated in their thirties, frequently with short follow-up periods. Therefore, information about cancer risk among infertile menopausal women is limited. We aimed to evaluate the risk of cancer among IVF patients treated at age 40 years and older, followed up for an extended period. DESIGN: Historical cohort study of all IVF patients treated at the age of 40 years or older at two university-affiliated IVF units in Jerusalem, Israel, between 1994 and 2002. Data were cross-linked with the Israel National Cancer Registry to 2016. Standardized incidence ratios (SIR) and 95% confidence intervals were computed by comparing the observed number of cancer cases with the expected cancer rate in the general Israeli population adjusted for age and year of birth. In addition, Kaplan-Meier analysis was conducted to account for the length of follow-up. RESULTS: A total of 501 patients were included in the analysis, with mean follow-up of 16.7 ± 3.7 years (range 2-22 years). Mean age at first IVF cycle was 42.3 years (±2.1). Mean number of IVF cycles was 3.2 ± 2.6 (range 1-15). Thirty-six women (7.2%) developed invasive cancer, compared with 47.2 expected cases; SIR 0.76 (95% CI 0.53 to 1.06); 22 women were diagnosed with invasive breast cancer, compared with 19.84 expected; SIR 1.11 (95% CI 0.69 to 1.68). CONCLUSIONS: Older women undergoing IVF treatment were not significantly associated with an excess risk of cancer at long-term follow up. Further studies, however, are needed to confirm these findings.

Postnatal steroid therapy is associated with autism spectrum disorder in children and adolescents of very low birth weight infants.

BACKGROUND: This study evaluates the association between major neonatal morbidities and autism spectrum disorder (ASD) in children and adolescents born of very low birth weight (VLBW). METHODS: Historical cohort study using the Israel national VLBW infant database linked with the Maccabi Healthcare Services (MHS) medical records. The study cohort comprised 4963 VLBW subjects born from 1999 to 2012, >1 year of age. Multivariable logistic regression analyses were used to assess factors associated with ASD. RESULTS: The diagnosis of ASD was confirmed in 113 children (2.3%). Infants with major neonatal morbidities had higher rates of ASD; however, in the multivariable analyses these were not significantly associated with ASD: severe intraventricular hemorrhage (OR 1.21 [95% CI 0.60-2.45]), post-hemorrhagic hydrocephalus (OR 1.77 [0.73-4.29]), periventricular leukomalacia (OR 1.02 [0.42-2.51]), severe retinopathy of prematurity (OR 1.91 [0.995-3.67]), and bronchopulmonary dysplasia (OR 1.44 [0.84-2.45]). Postnatal steroid therapy when included separately was associated with an OR of 1.97 [1.18-3.29] for ASD. This association remained significant when postnatal steroid therapy was included with each of the neonatal morbidities (ORs ranging from 1.91 to 2.11). CONCLUSIONS: This study suggests a significant association between postnatal steroid therapy and ASD in VLBW infants. This possible association should be considered in future studies evaluating potential risk factors for ASD in preterm infants.

Disordered eating behaviors in adolescents with celiac disease.

PURPOSE: Celiac disease (CD) is a chronic immune-mediated systemic disease characterized by inflammation and villous atrophy of the small intestine. A strict, lifelong gluten-free diet (GFD) is the only treatment for CD. Disordered eating behaviors (DEBs) prevail in adolescence and young adulthood, and confer a risk of developing into full-blown eating disorders. The aims of the current study were to assess the incidence and risk factors for DEBs among individuals with CD, and to examine an association between adherence to GFD and DEBs. METHODS: A cohort of 136 individuals with CD responded to a web-mediated survey that assessed DEBs and adherence to a GFD. The survey included demographic data (gender, age, weight, disease duration) and two self-rating questionnaires: the Eating Attitudes Test-26 and the gluten-free diet questionnaire. RESULTS: DEBs were found in 19% of female and 7% of male responders. These individuals were characterized by being overweight (p = 0.02), of an older age (p = 0.04) and female sex (p = 0.06). Strict adherence to a GFD was reported by 32% of the responders and was not correlated with age, disease duration, age at diagnosis of CD and with being overweight. CONCLUSIONS: Caregivers should be aware of the increased occurrence of DEBs in adolescents with CD, especially those who are overweight, older and of a female gender. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Deliveries following fertility preservation by ovarian tissue cryopreservation without autotransplantation-what should be expected?

OBJECTIVE: To evaluate the delivery rate and to characterize patients following ovarian tissue cryopreservation (OTCP) who did not undergo auto-transplantation. METHODS AND MATERIALS: All consecutive cancer patients admitted to our IVF unit, from January 2004 to December 2015, who underwent OTCP for the purpose of fertility preservation without autotransplantation were analyzed. The cohort included 338 patients and was linked to the National Live Birth registry of the Israel Ministry of Health in order to determine whether the women delivered following the cancer diagnosis. MAIN OUTCOME MEASURES: Delivery rate following OTCP without autotransplantation. RESULTS: During 6.4 years of follow-up, 30% of the patients delivered, with no differences in gravity, age at first diagnosis of cancer, type of malignancy, or the prevalence of relapse of malignancy between those who delivered and those who did not. Moreover, in multivariate analysis, those undergoing OTCP before the age of 30 and those suffering from breast cancer had significantly higher odds to conceive and deliver following cancer treatment without the need of autotransplantation. CONCLUSIONS: Further studies are required to elucidate the appropriate subgroup of patients with breast cancer under the age of 30 years, who will need OTCP. This information might aid both fertility specialists' counseling and their oncological patients in pursuing the appropriate fertility preservation strategy.

Increased prevalence of disordered eating in the dual diagnosis of type 1 diabetes mellitus and celiac disease.

BACKGROUND: Disordered eating behaviors (DEBs) may lead to full blown eating disorders. Both type 1 diabetes mellitus (T1DM) and celiac disease (CD) have been linked to DEBs. OBJECTIVE: To compare the presence of DEBs between adolescents and young adults with a dual diagnosis of T1DM and CD, and individuals with only one of the diagnoses. METHODS: Individuals with a dual diagnosis of T1DM and CD ("T1DM + CD group" n = 39), with a diagnosis of T1DM only ("T1DM group" n = 97) and with a diagnosis of CD only ("CD group" n = 267) filled the Eating Attitude Test-26 (EAT-26) questionnaire. Those with T1DM completed in addition to the Diabetes Eating Problem Survey-Revised (DEPS-R). RESULTS: The study population comprised of 403 individuals, of whom 65% were females. There were no statistically significant differences among the groups in distribution of sex, age, hemoglobin A1c (HbA1c) levels, age of disease diagnosis and duration. The prevalence of DEBs in the T1DM + CD group was 3-fold higher (26.0%) than in the T1DM (8.2%) and CD (8.2%) groups (P = .003). This trend was observed for both females and males. Multivariate analysis demonstrated that the T1DM + CD group had an increased risk for DEBs (odds ratio, OR: 4.7, 95% confidence interval, CI: 1.9-11.2, P = .001) after adjustment for age, sex, and body mass index. Additionally, being female, older and overweight increased the risk for DEBs. HbA1c values were not associated with an increased DEBs rate. CONCLUSIONS: Individuals with the dual diagnoses of T1DM and CD have an increased likelihood to develop DEBs compared to those with only one of these diagnoses.

Risk factors and epidemiology of pediatric ventriculoperitoneal shunt infection.

BACKGROUND: The aim of this study was to identify independent risk factors for cerebrospinal fluid shunt infection. METHODS: The medical records of all patients aged 0-18 years who underwent shunt-related surgery for the treatment of hydrocephalus at the present institution between January 1996 and December 2015 were reviewed. For each case, two randomly selected controls with no shunt infection, matched for year of surgery, were chosen. Demographic clinical and microbiological data were abstracted. RESULTS: A total of 1,570 shunt-related procedures met the inclusion criteria, yielding 68 infections (in 63 patients). The control group consisted of 132 infection-free patients. The average annual infection rate was 4.2% cases per year. The median time between shunt procedures to infection was 19 days (range, 1-2,181). On multivariate analysis, risk factors associated with increased risk for developing an infection included a history of two or more previous revisions (OR, 4.8; 95%CI: 1.5-15.9); and age <5 years (OR, 4.5; 95%CI 1.5-13.4). A neoplastic etiology for hydrocephalus was found to be a protective factor for shunt infection (P = 0.001). CONCLUSIONS: A history of shunt revision was the most significant risk factor in the development of subsequent shunt infection. Age >5 years was a protective factor. Future efforts should focus on modalities to optimize revision procedures and reduce the risk of subsequent infection.

Elevated Baseline Cortisol Levels Are Predictive of Bad Outcomes in Critically Ill Children.

OBJECTIVE: The definition of an adequate adrenal response in critically ill children continues to be controversial. We aimed to evaluate the cortisol levels at baseline and after adrenocorticotropin (ACTH) stimulation and determine their association to clinical outcome of critically ill children. METHODS: All children who underwent an ACTH test in the pediatric intensive care unit (PICU) in a tertiary medical center between 2006 and 2013 were included in the study. Data on age, sex, diagnosis, vasoactive-inotropic score, length of pediatric intensive care unit stay, and mortality were obtained. Laboratory variables included hematologic and chemistry data, arterial lactate, and total plasma cortisol levels at baseline and after ACTH stimulation. RESULTS: Ninety-nine patients (61 males; median [range] age, 2 [0-204] months) were enrolled. The mortality rate of children with a baseline cortisol level of 600 nmol/L or greater was 36% (12/33 patients) versus 18% (12/66 patients) for children with a baseline cortisol level of less than 600 nmol/L (odds ratio, 2.6 [95% confidence interval, 1-6.6]; P = 0.05). There was a positive correlation between baseline cortisol and lactate levels (r = 0.40, P < 0.0001), vasoactive-inotropic scores (r = 0.24, P = 0.02), and mortality (P = 0.05). There was no correlation between peak cortisol measured at the ACTH test or the delta increment of cortisol from baseline and mortality. CONCLUSIONS: A high baseline cortisol level in critically ill children was associated with more severe illness, higher lactate level, and a higher mortality rate. Routine baseline cortisol assessment is recommended to identify patients at high mortality risk.

Rehospitalization Through Childhood and Adolescence: Association with Neonatal Morbidities in Infants of Very Low Birth Weight.

OBJECTIVE: To evaluate the impact of major neonatal morbidities on the risks for rehospitalization in children and adolescents born of very low birth weight. STUDY DESIGN: An observational study was performed on data of the Israel Neonatal Network linked together with the Maccabi Healthcare Services medical records. After discharge from the neonatal intensive care unit, 6385 infants of very low birth weight born from 1995 to 2012 were registered with Maccabi Healthcare Services and formed the study cohort. Multivariable negative binomial regression models were calculated to estimate the adjusted relative risk (aRR) and 95% CI for hospitalization. RESULTS: Up to 18 years following discharge, 3956 infants were hospitalized at least once. The median age of follow-up was 10.7 years with total of follow-up of 67 454 patient years and 10 895 hospitalizations. The risks for rehospitalization were increased significantly for each of the neonatal morbidities: surgical necrotizing enterocolitis (NEC), aRR 2.71 (95% CI 2.08-3.53), intraventricular hemorrhage grades 3-4, 2.13 (1.85-2.46), periventricular leukomalacia (PVL), 1.83 (1.58-2.13), bronchopulmonary dysplasia, 1.94 (1.72-2.17), and retinopathy of prematurity stages 3-4, 1.59 (1.36-1.85). During the first 4 years, children with surgically treated NEC, intraventricular hemorrhage, PVL, or bronchopulmonary dysplasia had 1.5- to 2.5-fold greater risks for hospitalization compared with those without the specific morbidity. In the 11th-14th and 15th-18th years, respectively, surgically treated NEC was associated with a 3.05 (1.32-7.04) and 3.26 (0.99-10.7) aRR for hospitalization, and PVL was associated with a 2.67 (1.79-3.97) and 3.47 (2.03-5.92) aRR for hospitalization. CONCLUSIONS: Specific major neonatal morbidities as well as the number of morbidities were associated with excess risks of rehospitalization through childhood and adolescence.

Sexual lifestyle among young adults with type 1 diabetes.

BACKGROUND: Sexual lifestyles including sexual activity, problems, satisfaction, and the formation and maintenance of relationships are greatly affected by physical health. Data are limited regarding the sexual lifestyle of adolescents and young adults with type 1 diabetes mellitus (T1DM). Fear of hypoglycemic episodes during sexual intercourse and intimacy issues can impact individuals with T1DM. The aim of this study was to assess sexual lifestyles of individuals with T1DM. METHODS: Fifty-three patients with T1DM, 27 (51%) males, mean ± SD age 27.9 ± 8.3 years completed the Hypoglycemia Fear Survey-II and the Sex Practices and Concerns questionnaire. RESULTS: Thirty-seven (70%) reported they never or almost never had concerns in their sexual lifestyles that were related to their diabetes. None experienced severe hypoglycemia during sex, but 21 (40%) reported occasional mild hypoglycemic events. More than two-thirds do not take any measures to prevent hypoglycemia before sex (decreasing insulin dose, snacks, and measuring blood glucose levels). Fear of hypoglycemia during sex was reported by 18 (35%); those who reported increased fear experienced mild hypoglycemic events during sex (61.1% vs 26.5%, P = .01), were singles (94.4% vs 64.7%, P = .02), and had higher scores on the Worries subscale of the Hypoglycemia Fear Survey-II (42.8 ± 12.8 vs 34.9 ± 10.5, P = .04) compared with those who did not. CONCLUSIONS: Among young people with T1DM, most do not have concerns regarding sex that are related to their diabetes, and most do not take specific measures before or after sex. One-third, however, fear of hypoglycemia during sex, mostly singles and those who experienced hypoglycemia in the past. Caregivers should be aware and address these concerns. Copyright © 2016 John Wiley & Sons, Ltd.

The metabolic syndrome and its components in pediatric survivors of allogeneic hematopoietic stem cell transplantation.

Metabolic syndrome (MetS) is a known complication after hematopoietic stem cell transplantations (HSCT) that contributes to long-term morbidity. We assessed the prevalence of components of the MetS in pediatric survivors of allogeneic HSCT and identified associated risk factors. Thirty-eight patients, median age at HSCT, 8.5 years, were evaluated at a median of 3.9 years post-HSCT. Overweight or obesity was seen in 23.7% of the patients, 15.8% had hypertension, 15.8% had hypertriglyceridemia, and 13% had low high-density lipoprotein cholesterol levels according to age and gender. Four (10.5%) met the criteria of MetS; all were transplanted for malignant disease. Twelve patients (31.6%) had at least one component of the MetS. The 5-year probability of developing components of the MetS revealed that patients with BMI-Z score ≥0 at HSCT were significantly at higher risk than those with lower BMI-Z. Patients who developed components of the MetS had higher levels of insulin, homeostasis model assessment, uric acid, leptin, and lower adiponectin levels. Multivariable regression analysis revealed that BMI-Z-score >1.036 at time of evaluation was associated with 4.3-fold increased risk (P=.050) and adiponectin levels ≤6 µg/mL were associated with 6.7-fold increased risk of develop components of the MetS (P=.007). Overweight and obesity and adiponectin levels may be useful as markers in HSCT survivors.

Possible risk for cancer among children born following assisted reproductive technology in Israel.

BACKGROUND: Among children conceived by assisted reproductive technology (ART), increased risk of adverse birth outcomes has been observed, including multiple births, preterm births, and congenital malformations. Regarding cancer among ART-conceived children, findings are discrepant. METHODS: This is a historical cohort of 9,042 ART-conceived children and 211,763 spontaneously conceived (SC) children born from 1997 through 2004. The median duration of follow-up was 10.6 years (interquartile range 9.0-12.3) in the ART group and 9.3 years (interquartile range 8.0-10.6) in the SC group. The cohort database was linked with the Israel National Cancer Registry updated until December 31, 2011 using each child's personal identification number. RESULTS: Twenty-one cases of cancer were identified in the ART group (2.2 per 10,000 person-years), as compared to 361 cancer cases in the SC group (1.8 per 10,000 person-years). The relative risk (RR) for overall cancer in the ART group compared to the SC group adjusted for maternal characteristics was 1.18 (95% confidence interval [CI] 0.80-1.75). ART children had a significantly increased risk for specific cancers, although based on small number of cases, including two cases of retinoblastoma (RR 6.18, 95% CI 1.22-31.2), as well as four cases of renal tumors (RR 3.25, 95% CI 1.67-6.32). CONCLUSION: A statistically significant increased risk for two pediatric cancers was found. However, for overall types of cancer the risk estimate was elevated but not statistically significant. Further studies with larger sample size and longer follow-up time are warranted in order to either confirm or refute these findings.

Association between neonatal morbidities and head growth from birth until discharge in very-low-birthweight infants born preterm: a population-based study.

AIM: To evaluate the possible association between major neonatal morbidities and poor head growth from birth to discharge home in very-low-birthweight (VLBW) infants born preterm. METHOD: Population-based observational study comprising 12 992 infants (6340 male, 6652 female) of 24 to 32 weeks' gestation, and birthweight ≤1500g. Severe head growth failure (HGF) was defined as a decrease in head circumference z-score >2 z-scores, and moderate HGF as a decrease of 1 to 2 z-scores. Multinomial logistic regression analysis was applied to determine morbidities associated with HGF. RESULTS: Severe HGF occurred in 4.5% and moderate HGF in 20.9% of infants. Each unit increase in head circumference z-score at birth was associated with increased odds for severe and moderate HGF (odds ratios [OR] 5.29, 95% confidence intervals [CI] 4.67-6.00, and OR 2.38, 95% CI 2.23-2.54 respectively). Both severe and moderate HGF were associated with respiratory distress syndrome (OR 2.03, 95% CI 1.58-2.62, and OR 1.66, 95% CI 1.48-1.85 respectively); bronchopulmonary dysplasia (OR 3.38, 95% CI 2.33-4.91, and OR 1.87, 95% CI 1.52-2.30 respectively); necrotizing enterocolitis (OR 2.89, 95% CI 2.04-4.09, and OR 1.72, 95% CI 1.38-2.16 respectively), and sepsis (OR 2.06, 95% CI 1.69-2.50, and OR 1.38, 95% CI 1.24-1.53 respectively). INTERPRETATION: Major neonatal morbidities were associated with HGF in VLBW infants born preterm. Identification of whether this is a direct effect of these morbidities or mediated through nutritional or growth factors may enable interventions to improve postnatal head growth of infants born preterm.

Pregnancy and Birth Outcomes Among Primiparae at Very Advanced Maternal Age: At What Price?

OBJECTIVES: In light of the potential physical and emotional costs to both woman and child, this study was conducted to assess pregnancy complications and birth outcomes in primiparae at very advanced maternal age (VAMA, aged ≥45) compared to younger primiparae. METHODS: Retrospective cohort study comparing 222 VAMA primiparae and a reference group of 222 primiparae aged 30-35, delivering at Sheba Medical Center from 2008 through 2013. RESULTS: VAMA primiparae were more likely than younger primiparae to be single, to have chronic health conditions, and higher rates of gestational diabetes mellitus (GDM), gestational-hypertension (GHTN) and preeclampsia-eclampsia. VAMA primiparae conceived mostly by oocyte donation. They were more likely to be hospitalized during pregnancy, to deliver preterm and by cesarean birth. Infants of VAMA primiparae were at greater risk for low birthweight and Neonatal Intensive Care Unit admission. There were no differences in outcomes between VAMA primiparae with or without preexisting chronic conditions, or between those aged 45-49 and ≥50. In multivariable analysis VAMA was an independent risk factor for GDM, GHTN and preeclamsia-eclampsia, with adjusted odds ratio of 2.38 (95 % CI 1.32, 4.29), 5.80 (95 % CI 2.66, 12.64) and 2.45 (95 % CI 1.03, 5.85); respectively. The effect of age disappeared in multiple pregnancies. CONCLUSIONS: Primiparity at VAMA holds a significant risk for adverse pregnancy and birth outcomes. The absence of chronic medical conditions or the use of a young oocyte donor does not improve these outcomes. Multiple pregnancies hold additional risk and may diminish the effect of age. Primiparity at an earlier age should be encouraged.