The diagnosis of depression or anxiety treated by SSRIs has become relatively common in women of childbearing age. However, the impact of gestational SSRI treatment on newborn thyroid function is lacking. We explored the impact of gestational SSRI treatment on newborn thyroid function as measured by the National Newborn Screening (NBS) Program and identified contributory factors. An observational large-scale study of mother-infant dyads of liveborn infants delivered between 2011 and 2022. The Israeli NBS Program thyroid dataset [total thyroxine (TT4) obtained between 36-72 h after delivery] was linked with the electronic medical records of mothers and their infants born at Lis Maternity and Women's Hospital, to generate a unified database. The MDClone big data platform was utilized to extract maternal, perinatal, and neonatal characteristics from the medical records of mother-infant dyads. Only term liveborn infants born to mothers without documented thyroid disease and/or chronic medication administration, except for SSRIs, were included in order to minimize potential confounding effects on the infant's thyroid function. Group stratification relied on the documentation of gestational SSRIs treatment. The variables of interest were maternal, pregnancy, delivery, and perinatal characteristics of the mother-infant dyads. Multivariable forward linear regression model was applied to evaluate explanatory variables for newborn total thyroxine (TT4) levels. Out of 105,928 infant-mother dyads, 2321(2.2%) mothers had been treated with SSRIs during pregnancy. The SSRI-treated mothers were older (34.8 ± 4.7 vs 32.6 ± 4.8 years, p < 0.001) and had a higher pre-pregnancy body mass index (23.4 ± 4.5 vs 22.7 ± 4.1, p < 0.001), but similar mean weight gain (13 kg) during pregnancy. Cesarean delivery was more common among SSRI-treated mothers than in the general population (p < 0.001). Infants of SSRI-treated mothers had lower WHO-classified birthweight z-scores (-0.25 ± 0.93 vs -0.04 ± 0.92, p < 0.001) and a higher rate of small-for-gestational-age infants (13.4% vs 8.2%, p < 0.001). A multivariable forward linear regression model revealed that SSRI treatment during pregnancy was not a significant contributor to TT4 levels (p = 0.497). SSRI treatment during pregnancy had no direct effect upon the newborn's adaptation of the hypothalamic-pituitary-thyroidal axis, but several other maternal and delivery characteristics were revealed to possibly impact newborn thyroid function.
Abstract The Nancy Histological Index (NHI) is used to score histologic disease activity in patients with ulcerative colitis (UC). Our goal was to assess the utility of NHI at diagnosis in predicting clinical outcomes in pediatric patients with UC, in comparison to clinical and endoscopic scores. We retrospectively reviewed data at diagnosis of 106 children with UC (59 [55.7%] females; median age 14.4 [11.2–15.9] years, median Pediatric Ulcerative Colitis Activity Index [PUCAI] 35 [25–55]). During a follow‐up of 116 (55–171) weeks, 33 patients (31.1%) required azathioprine therapy, and 32 (30.2%) were escalated to anti‐tumor necrosis factor alpha (anti‐TNFa). The PUCAI and Mayo endoscopic scores at diagnosis were significantly associated with escalation to anti‐TNFa ( p = 0.036 and p = 0.02, respectively), but not with initiation of azathioprine or subsequent acute severe colitis (ASC) events. However, the NHI was not associated with subsequent immunomodulators or anti‐TNFa therapy ( p = 0.42 and p = 0.78, respectively), nor with future ASC events ( p = 0.70). In conclusion, the NHI failed to predict clinical outcomes in newly diagnosed pediatric patients with UC.
Background: Graves’ disease has been associated with adverse pregnancy, labor and delivery, and neonatal outcomes. Thyroid function levels, assessed during newborn screening (NBS), can serve as indicators of the adaptation in the hypothalamic-pituitary-thyroid axis. We utilized data from the national thyroid NBS program to investigate the characteristics of the mother-infant dyad of term infants born to mothers with past or active Graves’ disease. Methods: The dataset of the Israeli NBS for thyroid function was linked with the electronic records of a tertiary medical center to generate a unified database of mothers and their term infants born between 2011 and 2021. The MDClone big data platform extracted maternal, pregnancy, disease course, labor and delivery, and neonatal characteristics of the mother-infant dyads. Results: Out of 103,899 registered mother-infant dyads, 292 (0.3%) mothers had past or active Graves’ disease. A forward multivariate linear regression demonstrated that Graves’ disease did not significantly affect NBS total thyroxine (TT4) levels (p=0.252). NBS TT4 levels in infants born to mothers with active Graves’ disease were higher than those observed in the general Israeli population (p<0.001). Mothers with Graves’ disease more frequently used assisted reproductive technology (12.7% vs 9.0%, respectively, p=0.012; odds ratio [OR] 1.46 [95% confidence interval [CI] 1.03–2.07], p=0.031), and had more gestational hypertension (3.9% vs 1.1%, p<0.001; OR 3.53 [95%CI 1.92-6.47], p<0.001), proteinuria (2.5% vs 0.9%, p<0.001; OR 3.03 [95% CI1.43-6.45], p=0.004), cesarean sections (26.4% vs 19.7%, p=0.029; OR 1.46 [95%CI 1.13-1.90], p=0.004), prelabor rupture of membranes (15.4% vs 4.1%, p<0.001; OR 4.3 [95%CI 3.13-5.91], p<0.001), and placental abnormalities (5.1% vs 2.0%, p<0.001; OR 2.64 [95%CI 1.57-4.44]; p<0.001). Their infants had lower adjusted birthweight z-scores (-0.18±0.94 vs -0.03±0.90, p=0.007) and were more likely to be small for gestational age (12.0% vs 8.1%, p=0.005; OR 1.54 [95%CI 1.08-2.19], p=0.018). Conclusions: Neonatal thyroid function levels were affected by maternal Graves’ disease only when the disease was active during gestation. Moreover, maternal Graves' disease was also associated with an increased risk of adverse outcomes for the mother-infant dyad.
Abstract Disclosure: A. Brener: None. O. Raviv: None. E. Cohen-Sela: None. M. Yackobovitch-Gavan: None. S. Almashanu: None. R. Marom: None. L. Hiersch: None. Y. Lebenthal: None. Background: Clinical depression treated by selective serotonin reuptake inhibitors (SSRIs) has become relatively common in women of childbearing age. The effect of gestational exposure to SSRIs on the newborn’s hypothalamic-pituitary-thyroid postnatal adaptation has not yet been determined. We aimed to investigate the characteristics of the mother–infant dyad of term infants of mothers treated with SSRIs for depression during pregnancy. Methods: This observational study included mother-infant dyads of infants delivered at term in a single tertiary medical center between 2011 and 2021. Data on maternal, pregnancy, delivery, and perinatal characteristics of the mother-infant dyads were retrieved from the hospital’s electronic database. The clinical data were linked with the newborn thyroid screening results of total thyroxin (TT4) obtained at 48-72 hours since delivery. Excluded from analysis were mothers with other chronic medical conditions and newborns with genetic syndromes. Primary outcome measures were newborn TT4 levels and fetal growth as expressed by neonatal birthweight z-scores (WHO charts). Results: SSRI anti-depression treatment during gestation was reported in 2577 (2.4%) out of 106,173 infant-mother dyads. Mothers treated with SSRIs were older (35.0±4.8 vs 32.6±4.8 years, p<0.001), had a higher pre-pregnancy body mass index (23.4±4.5 vs 22.7±4.1, p<0.001) and a similar mean weight gain of 13 kg during pregnancy. Elective and emergent cesarean deliveries were more common among SSRI-treated mothers (14.8% vs 11.1% and 16.5% vs 8.6%, respectively, p<0.001). Infants of those mothers were born earlier (gestational age [GA] 38.7±1.9 vs 39.5±11.5 weeks, p<0.001), had lower birthweight z-scores (-0.48±1.24 vs -0.04±0.92, p<0.001) and lower TT4 levels (14.7±3.9 vs 15.0±3.7, p=0.001). A multivariate linear regression model revealed that sex, GA and birthweight z-score were highly significant contributors to TT4 levels (p<0.001 for all), while SSRI treatment during pregnancy was not (p=0.497). Conclusions: Our findings suggest that anti-depressant use of SSRIs during pregnancy does not have a direct effect on the postnatal adaptation of the hypothalamic-pituitary-thyroidal axis. However, differences in fetal growth and in characteristics of delivery may determine newborn thyroid function. Presentation: Friday, June 16, 2023
Abstract Background Intensification of adalimumab (ADL) dosing to weekly 40 mg injections, in response to low drug levels, has been shown to provide beneficial outcomes in pediatric patients with Crohn’s disease (CD). Our study aimed to evaluate the safety and efficacy of weekly 80 mg ADL administration in children with CD. Methods In this retrospective cohort study conducted across five Israeli centers, we reviewed the medical records of pediatric CD patients who received a high dose of ADL 80 mg weekly injections between 2016 and 2023. Collected data included demographic characteristics, disease features, laboratory studies, and treatment outcomes. Results Thirty-two children with CD were included: mean age 15.8 (±1.7) years at intensification, 21 male (66%), 18 (56%) with L3 phenotype. The median time to ADL 80 mg intensification from ADL induction was 48.4 weeks (IQR 23.1-122.5). The mean weighted Pediatric Crohn's Disease Activity Index (wPCDAI) was 28.5 (±16.9) at the time of intensification and the median calprotectin and C-reactive protein levels were 937 μg/g (IQR 540-1410) and 1.3 mg/dL (IQR 0.6-5.2), respectively. Clinically active disease was the main reason for ADL intensification (30, 94%). Baseline ADL levels were available in 30 patients (94%) with a median of 3.8 μg/mL (IQR 2.4-7.2). Among these, 23 children (77%) failed to achieve a target of ≥ 7.5 μg/mL. The median follow-up duration from the intensification dose was 91.2 weeks (IQR 53.6-149.1). Corticosteroids were required in 5/32 (15.6%) children, with a median time of 32.3 weeks (IQR 10.7-51.3) from intensification. There was no statistically significant difference in steroid utilization rates between children who achieved a target baseline drug level of ≥ 7.5 μg/mL and those who did not (p=0.934). Thirteen individuals (41%) discontinued ADL treatment, within a median of 24.7 weeks (IQR 11.7-57.1) from intensification. CD-related exacerbation, hospitalization, and surgery rates were 9 (28%), 4 (13%), and 2 (6%), respectively. No statistically significant differences were found in exacerbation (p=0.406), hospitalization (p=0.322), or surgery rates (p=0.427) between children who achieved a baseline ADL trough concentration level of ≥ 7.5 μg/mL and those who did not. Overall, ADL intensification was safe, but 3 (9%) patients developed new-onset psoriasis. Conclusion Our findings support the safety and efficacy of administering ADL at a weekly dosage of 80 mg as maintenance therapy in pediatric patients with moderate to severe CD.
ABSTRACT Aim To explore the relationships between body composition, indices of hepatic fibrosis, and sonographic evidence of hepatic steatosis in children with overweight and obesity. Methods One hundred and seventy individuals (age 12.7 ± 3.4 years, 38.2% boys) with overweight/obesity (BMI z ‐score 2.02 ± 0.54) underwent bioelectrical impedance analysis (fat percentage, truncal‐to‐total fat ratio, muscle‐to‐fat ratio [MFR]). Hepatic assessments included ultrasonography to detect liver steatosis, alanine transaminase (ALT), aspartate aminotransferase (AST)/ALT ratio, and nonalcoholic fatty liver disease fibrosis score (NFS). A forward logistic regression model, adjusting for sex, age, and socio‐economic position, was conducted. Results The odds for sonographic hepatic steatosis increased by 3.8‐fold for each SD decrease in MFR z ‐score (OR = 0.263, 95% CI [0.067–1.031], p = 0.05). The strongest correlation among boys was between MFR z ‐score and AST/ALT ratio ( r = 0.530, p < 0.001), whereas the strongest correlation among girls was between fat percentage and NFS ( r = 0.503, p < 0.001). Individuals with sonographic hepatic steatosis had higher fat mass ( p = 0.003), lower MFR z ‐score ( p = 0.020), greater insulin resistance ( p = 0.018), and atherogenic dyslipidemic index ( p = 0.037) compared to those without. Conclusions We identified sex differences in the association between body composition and hepatic fibrosis indices. The relationship between adverse body composition and increased odds of hepatic steatosis underscores the importance of its assessment within this at‐risk population.
