Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia.

BACKGROUND: This trial aimed to assess the efficacy, acceptability, and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia in Asia. METHODS: Between August 1, 2019, and February 28, 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from 10 regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular 6-week intervals, one cluster was randomized to transit from nonintervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm preeclampsia using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm preeclampsia ≥1 in 100, received low-dose aspirin from <16 weeks until 36 weeks. RESULTS: Overall, 88.04% (42 897 of 48 725) of women agreed to undergo first-trimester screening for preterm preeclampsia. Among those identified as high-risk in the intervention phase, 82.39% (2919 of 3543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm preeclampsia between the intervention and non-intervention phases (adjusted odds ratio [aOR], 1.59 [95% CI, 0.91-2.77]). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm preeclampsia (aOR, 0.59 [95% CI, 0.37-0.92]). In addition, it correlated with 54%, 55%, and 64% reduction in the incidence of preeclampsia with delivery at <34 weeks (aOR, 0.46 [95% CI, 0.23-0.93]), spontaneous preterm birth <34 weeks (aOR, 0.45 [95% CI, 0.22-0.92]), and perinatal death (aOR, 0.34 [95% CI, 0.12-0.91]), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events. CONCLUSIONS: The implementation of the screen-and-prevent strategy for preterm preeclampsia is not associated with a significant reduction in the incidence of preterm preeclampsia. However, low-dose aspirin effectively reduces the incidence of preterm preeclampsia by 41% among high-risk women. The screen-and-prevent strategy for preterm preeclampsia is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm preeclampsia on a global scale. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03941886.

Incidence of neonatal sepsis after universal antenatal culture-based screening of group B streptococcus and intrapartum antibiotics: A multicentre retrospective cohort study.

OBJECTIVE: To compare the incidences of early and late-onset neonatal sepsis, including group B streptococcus (GBS) and Escherichia coli (E. coli) before and after implementation of universal screening and intrapartum antibiotics prophylaxis (IAP). DESIGN: Retrospective cohort study. SETTING: Eight public hospitals and 31 Maternal and Child Health Centres (in Hong Kong. POPULATION: 460 552 women attending routine antenatal service from 2009 to 2020. METHODS: Universal culture-based GBS screening has been offered to eligible women since 2012. Total births, GBS screening tests, maternal GBS colonisation and neonatal sepsis with positive blood or cerebrospinal fluid were retrieved from clinical and laboratory database. MAIN OUTCOME MEASURES: Maternal GBS colonisation rate, early- and late-onset neonatal sepsis (including GBS and E. coli). RESULTS: Of 318 740 women with universal culture-based screening, 63 767 women (20.0%) screened positive. After implementation of GBS screening and IAP, the incidence of early-onset neonatal sepsis decreased (3.25 versus 2.26 per 1000 live births, p < 0.05), including those caused by GBS (1.03 versus 0.26 per 1000 live births, p < 0.05). Segmented regression showed that change in early-onse GBS sepsis incidence after screening was the only significant variable in the outcome trend. There was no significant evidence of increase in incidence of late-onset neonatal sepsis including those caused by GBS. CONCLUSIONS: Universal culture-based GBS screening and IAP were associated with reduction in early-onset neonatal sepsis including GBS disease. Although an increase in incidence of late-onset neonatal sepsis including those caused by GBS cannot be totally ruled out, we did not identify significant evidence that this occurred.

Natural history of infants with vitamin D deficiency in Hong Kong.

BACKGROUND AND OBJECTIVES: The usual recommended intake of vitamin D for healthy infants is 400 international unit (IU) daily. However, a high dose of vitamin D at 2000-3000 IU daily is needed for those with vitamin D deficiency (VDD). This study aimed to assess the natural history of a group of healthy infants with VDD and the associated factors for persistent VDD. METHODS AND STUDY DESIGN: Healthy infants detected to have VDD (25OHD <25 nmol/L) in a population study were followed, and their demographics and clinical data were collected. RESULTS: One hundred and thirty-one subjects (boys = 66%) were included. Their first serum 25OHD was taken at a median age of 87.5 days. None were treated with high-dose vitamin D supplements, but some have been given vitamin D at 400 IU daily. They were assessed again at the median age of 252.5 days when 15 remained to have VDD and 26 were in the insufficient range (25 - 49.9nmol/L). All persistent VDD children were on exclusive breastfeeding. Exclusive breastfeeding and no vitamin D supplementation were significant risk factors for persistent vitamin D insufficiency (<50nmol/L). CONCLUSIONS: Persistent VDD is common among infants exclusively breastfeeding and those who did not receive vitamin D supplementation.

Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study.

BACKGROUND: The influence of maternal levothyroxine treatment during pregnancy remains unclear. This study aimed to evaluate the associations of maternal levothyroxine treatment during pregnancy with the birth and neurodevelopmental outcomes in offspring. METHODS: This population-based cohort study was conducted among pregnant women using the Hong Kong Clinical Data Analysis and Reporting System. Mother-child pairs in Hong Kong from 2001 to 2015 were included and children were followed up till 2020. We defined the exposure group as mothers who were exposed to levothyroxine during pregnancy. Preterm birth and small for gestational age (SGA) were included as birth outcomes. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) were included as neurodevelopmental outcomes. Odds ratios (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) were evaluated to assess the association of gestational levothyroxine use with offspring birth and neurodevelopmental outcomes respectively, using propensity score fine-stratification weighting and a Cox proportional hazards regression model. RESULTS: Among 422,156 mother-child pairs, 2125 children were born from mothers exposed to levothyroxine during pregnancy. A significantly increased risk of preterm birth was observed in children with maternal levothyroxine exposure during pregnancy, when compared to mothers who had no history of thyroid-related diagnoses or prescriptions (weighted OR [wOR]: 1.22, 95% CI: 1.07, 1.39). Similarly, an increased risk of preterm birth was found among children of gestational levothyroxine users, when compared to children of mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16, 95% CI: 1.09, 4.25). Sensitivity analysis, by excluding mothers exposed to psychotropic or antiepileptic medications before or during pregnancy, also indicated a similar increased risk of preterm birth regarding the gestational use of levothyroxine (wOR: 1.26, 95% CI: 1.10, 1.45). No significant association was observed for the risk of SGA, ADHD, and ASD. CONCLUSIONS: There is no evidence that gestational use of levothyroxine is associated with SGA, ADHD, or ASD in offspring. Gestational levothyroxine treatment is associated with a higher risk of preterm birth. Such risk might be confounded by the underlying maternal thyroid disease itself, however, we cannot completely exclude the possible effect of gestational L-T4 treatment on offspring preterm birth. Our findings provided support to the current guidelines on the cautious use of levothyroxine treatment during pregnancy.

Four cases of cervical varices without placenta praevia: Presentation, diagnosis, managements, and literature review.

Cervical varices are a rare condition characterized by recurrent antepartum hemorrhage and less than 20 cases were reported in the literature. It is usually associated with placenta previa. We herein describe four cases of cervical varices without placenta previa. Meticulous speculum examination, ultrasonography with Doppler and colposcopy are essential for establishing the diagnosis and assessing the extent of the cervical varix. We propose to classify it as the apparent external os type or ultrasonography-based endocervical type. Most cases presented in the literature were delivered by cesarean section. Nevertheless, one of our cases was a successful vaginal delivery. Our case illustrates that vaginal delivery is possible in isolated cervical varices. More case reports are needed to have a better understanding of this rare entity.

The Use of Somatex Shunt for Fetal Pleural Effusion: A Cohort of 8 Procedures.

INTRODUCTION: Fetal pleural effusion may require in utero shunting which is associated with procedure-related complications. OBJECTIVE: To evaluate the efficacy and complications of the newly designed Somatex shunt in treating fetal pleural effusion. METHODS: Consecutive cases with primary fetal pleural effusion who were treated with the Somatex shunt between 2018 and 2019 were evaluated. Perinatal outcomes and complications were retrospectively analyzed. RESULTS: There were 6 cases of unilateral and 1 case of bilateral pleural effusion, and hence a total of 8 pleuroamniotic shunting procedures were performed. The median gestational age at diagnosis and shunting was 20.7 and 22.6 weeks, respectively. All 8 procedures were successful, achieving complete in utero drainage. All but one were live births (85.7%) with a median gestational age of 38 weeks. The single case of in utero death occurred 4.7 weeks after successful shunting, and no cause could be identified after autopsy. The rates of preterm birth and premature rupture of membranes were 33.3% (2/6) and 16.7% (1/6), respectively. Four of the 8 procedures (50%) had minor shunt-related complications such as dislodgement and entrapment, occurring at a median of 7.7 weeks after shunting. None of the shunts became blocked. CONCLUSIONS: The Somatex shunt is effective in relieving fetal pleural effusions with good survival rate. Overall, it was a safe instrument, though minor shunt complications occurred.

Prospective evaluation of screening performance of first-trimester prediction models for preterm preeclampsia in an Asian population.

BACKGROUND: The administration of aspirin <16 weeks gestation to women who are at high risk for preeclampsia has been shown to reduce the rate of preterm preeclampsia by 65%. The traditional approach to identify such women who are at risk is based on risk factors from maternal characteristics, obstetrics, and medical history as recommended by the American College of Obstetricians and Gynecologists and the National Institute for Health and Care Excellence. An alternative approach to screening for preeclampsia has been developed by the Fetal Medicine Foundation. This approach allows the estimation of patient-specific risks of preeclampsia that requires delivery before a specified gestational age with the use of Bayes theorem-based model. OBJECTIVE: The purpose of this study was to examine the diagnostic accuracy of the Fetal Medicine Foundation Bayes theorem-based model, the American College of Obstetricians and Gynecologists, and the National Institute for Health and Care Excellence recommendations for the prediction of preterm preeclampsia at 11-13+6 weeks gestation in a large Asian population STUDY DESIGN: This was a prospective, nonintervention, multicenter study in 10,935 singleton pregnancies at 11-13+6 weeks gestation in 11 recruiting centers across 7 regions in Asia between December 2016 and June 2018. Maternal characteristics and medical, obstetric, and drug history were recorded. Mean arterial pressure and uterine artery pulsatility indices were measured according to standardized protocols. Maternal serum placental growth factor concentrations were measured by automated analyzers. The measured values of mean arterial pressure, uterine artery pulsatility index, and placental growth factor were converted into multiples of the median. The Fetal Medicine Foundation Bayes theorem-based model was used for the calculation of patient-specific risk of preeclampsia at <37 weeks gestation (preterm preeclampsia) and at any gestation (all preeclampsia) in each participant. The performance of screening for preterm preeclampsia and all preeclampsia by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index, and placental growth factor (triple test) was evaluated with the adjustment of aspirin use. We examined the predictive performance of the model by the use of receiver operating characteristic curve and calibration by measurements of calibration slope and calibration in the large. The detection rate of screening by the Fetal Medicine Foundation Bayes theorem-based model was compared with the model that was derived from the application of American College of Obstetricians and Gynecologists and National Institute for Health and Care Excellence recommendations. RESULTS: There were 224 women (2.05%) who experienced preeclampsia, which included 73 cases (0.67%) of preterm preeclampsia. In pregnancies with preterm preeclampsia, the mean multiples of the median values of mean arterial pressure and uterine artery pulsatility index were significantly higher (mean arterial pressure, 1.099 vs 1.008 [P<.001]; uterine artery pulsatility index, 1.188 vs 1.063[P=.006]), and the mean placental growth factor multiples of the median was significantly lower (0.760 vs 1.100 [P<.001]) than in women without preeclampsia. The Fetal Medicine Foundation triple test achieved detection rates of 48.2%, 64.0%, 71.8%, and 75.8% at 5%, 10%, 15%, and 20% fixed false-positive rates, respectively, for the prediction of preterm preeclampsia. These were comparable with those of previously published data from the Fetal Medicine Foundation study. Screening that used the American College of Obstetricians and Gynecologists recommendations achieved detection rate of 54.6% at 20.4% false-positive rate. The detection rate with the use of National Institute for Health and Care Excellence guideline was 26.3% at 5.5% false-positive rate. CONCLUSION: Based on a large number of women, this study has demonstrated that the Fetal Medicine Foundation Bayes theorem-based model is effective in the prediction of preterm preeclampsia in an Asian population and that this method of screening is superior to the approach recommended by American College of Obstetricians and Gynecologists and the National Institute for Health and Care Excellence. We have also shown that the Fetal Medicine Foundation prediction model can be implemented as part of routine prenatal care through the use of the existing infrastructure of routine prenatal care.

Pathway-specific modulatory effects of neuromuscular electrical stimulation during pedaling in chronic stroke survivors.

BACKGROUND: Neuromuscular electrical stimulation (NMES) is extensively used in stroke motor rehabilitation. How it promotes motor recovery remains only partially understood. NMES could change muscular properties, produce altered sensory inputs, and modulate fluctuations of cortical activities; but the potential contribution from cortico-muscular couplings during NMES synchronized with dynamic movement has rarely been discussed. METHOD: We investigated cortico-muscular interactions during passive, active, and NMES rhythmic pedaling in healthy subjects and chronic stroke survivors. EEG (128 channels), EMG (4 unilateral lower limb muscles) and movement parameters were measured during 3 sessions of constant-speed pedaling. Sensory-level NMES (20 mA) was applied to the muscles, and cyclic stimulation patterns were synchronized with the EMG during pedaling cycles. Adaptive mixture independent component analysis was utilized to determine the movement-related electro-cortical sources and the source dipole clusters. A directed cortico-muscular coupling analysis was conducted between representative source clusters and the EMGs using generalized partial directed coherence (GPDC). The bidirectional GPDC was compared across muscles and pedaling sessions for post-stroke and healthy subjects. RESULTS: Directed cortico-muscular coupling of NMES cycling was more similar to that of active pedaling than to that of passive pedaling for the tested muscles. For healthy subjects, sensory-level NMES could modulate GPDC of both ascending and descending pathways. Whereas for stroke survivors, NMES could modulate GPDC of only the ascending pathways. CONCLUSIONS: By clarifying how NMES influences neuromuscular control during pedaling in healthy and post-stroke subjects, our results indicate the potential limitation of sensory-level NMES in promoting sensorimotor recovery in chronic stroke survivors.

Women's uptake of non-invasive DNA testing following a high-risk screening test for trisomy 21 within a publicly funded healthcare system: findings from a retrospective review.

OBJECTIVE: The objective of the study was to evaluate the uptake of non-invasive cell-free fetal DNA screening test (NIDT) after a high-risk screening result for trisomy 21 METHODS: Association between maternal and pregnancy characteristics on women's test choice was assessed after adjusting for confounding factors in Hong Kong Chinese women who had a high-risk (term risk ≥1:250) first-trimester or second-trimester screening test at three public hospitals. Main outcome measures were rate of declining further testing and obstetric and maternal factors impacting on patient's selection of testing options. RESULTS: Compared with the pre-NIDT period, the availability of NIDT resulted in a 45% (P < 0.001) reduction in the rate of refusal for further testing and a decrease from 92.2% to 66.7% in the use of invasive diagnostic test after a positive screening test. Nulliparous women with a spontaneous [adjusted odds ratio (aOR) = 2.18, 95% confidence interval (CI) 1.63-2.92] or assisted reproduction pregnancy (aOR = 3.95, 95% CI 1.6-9.32) were more likely to choose NIDT. Women with an adjusted risk of '>1:10' (aOR = 7.36, 95% CI 4.22-12.8) and '1:10 to 1:50' (aOR = 1.53, 95% CI 1.01-2.32) were more likely to opt for chorionic villi sampling or amniocentesis. CONCLUSIONS: NIDT reduced the refusal rate. Uptake of NIDT was highest in pregnancies of nulliparous women.

Intimate partner violence during pregnancy: To screen or not to screen?

Intimate partner violence (IPV) during pregnancy emerges as a compelling and urgent concern within the domain of public health, casting a long shadow over a substantial cohort of women. Its pernicious consequences extend beyond the individual, enveloping the well-being of both the mother and the fetus, giving rise to an elevated risk of preterm birth, low birth weight, fetal harm, and maternal psychological distress, including depression, anxiety, post-traumatic stress disorder, and, tragically, maternal mortality. Despite the prevalence of IPV being comparable to other conditions like gestational diabetes and preeclampsia, a universal screening protocol for IPV remains absent globally. We reviewed the clinical guidelines and practices concerning IPV screening, painstakingly scrutinizing their contextual nuances across diverse nations. Our study unveils multifaceted challenges of implementing universal screening. These hurdles encompass impediments to victim awareness and disclosure, limitations in healthcare providers' knowledge and training, and the formidable structural barriers entrenched within healthcare systems. Concurrently, we delve into the potential biomarkers intricately entwined with IPV. These promising markers encompass inflammatory indicators, epigenetic and genetic influences, and a diverse array of chemical compounds and proteins. Lastly, we discussed various criteria for universal screening including (1) valid and reliable screening tool; (2) target population as pregnant women; (3) scientific evidence of screening programme; and (4) integration of education, testing, clinical services, and programme management to minimise the challenges, which are paramount. With the advancement of digital technology and various biomarkers identification, screening and detecting IPV in clinical settings can be conducted systemically. A systems-level interventions with academia-community-indutrial partnerships can help connect pregnant women to desire support services to avoid adverse maternal and child health outcomes.

Intimate Partner Violence Against Women Before, During, and After Pregnancy: A Meta-Analysis.

Intimate partner violence (IPV) against pregnant women negatively impacts women's and infants' health. Yet inconsistent results have been found regarding whether pregnancy increases or decreases the risk of IPV. To answer this question, we systematically searched for studies that provided data on IPV against women before pregnancy, during pregnancy, and after childbirth. Nineteen studies met our selection criteria. We meta-analyzed the nineteen studies for the pooled prevalence of IPV across the three periods and examined study characteristics that moderate the prevalence. Results showed the pooled prevalence estimates of IPV were 21.2% before pregnancy, 12.8% during pregnancy and 14.7% after childbirth. Although these findings suggest a reduction in IPV during pregnancy, our closer evaluation of the prevalence of IPV after childbirth revealed that the reduction does not appear to persist. The prevalence of IPV increased from 12.8% within the first year after childbirth to 24.0% beyond the first year. Taken together, we should not assume pregnancy protects women from IPV, as IPV tends to persist across a longer-term period. Future studies are needed to investigate if IPV transits into other less obvious types of violence during pregnancy. Moderator analyses showed the prevalence estimates significantly varied across countries by income levels and regions.

Trajectories and predictors of depressive symptoms among pregnant women: A 3-year longitudinal study.

OBJECTIVE: Not all women experience the same changes in depression from pregnancy through the years following childbirth, but the patterns of prenatal and postnatal depression are underexplored. This study investigated the trajectories and associated predictors of depressive symptoms in women from pregnancy through the first 3 years postpartum. METHOD: We followed 340 pregnant women from an antenatal clinic in Hong Kong, first at 20-24 weeks of gestation, then at 4 weeks after childbirth, and again at 3 years after childbirth. Pregnant women reported their depressive symptoms whether they had intimate partner violence, health conditions, adverse childhood experiences, family support, and perceived partner involvement. Latent class growth analysis was applied to identify distinct trajectories of depression, and binary logistic regressions were performed to analyze predictors of trajectories. RESULTS: We found that 26.5% of women showed clinical depressive symptoms at 20-24 weeks of gestation, 9.7% at 4 weeks after childbirth, and 12.6% at 3 years after childbirth. Two classes were identified: a low-stable group (86.2%) and a relapsing/remitting group (13.8%). Women with a history of trauma (i.e., intimate partner violence and adverse childhood experiences) and mental health difficulties were more likely to be classified in the relapsing/remitting group than in the low-stable group. Family support and partner emotional involvement appeared to protect the women from suffering relapsing/remitting depression. CONCLUSIONS: The findings highlight the importance of screening for depression throughout pregnancy and extending several years postpartum. Distinguishing the different trajectories of depression and identifying its associated factors are critical to providing targeted interventions to the most vulnerable women (i.e., a relapsing/remitting group in the present study). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Validation of the first-trimester machine learning model for predicting pre-eclampsia in an Asian population.

OBJECTIVES: To evaluate the performance of an artificial intelligence (AI) and machine learning (ML) model for first-trimester screening for pre-eclampsia in a large Asian population. METHODS: This was a secondary analysis of a multicenter prospective cohort study in 10 935 participants with singleton pregnancies attending for routine pregnancy care at 11-13+6 weeks of gestation in seven regions in Asia between December 2016 and June 2018. We applied the AI+ML model for the first-trimester prediction of preterm pre-eclampsia (<37 weeks), term pre-eclampsia (≥37 weeks), and any pre-eclampsia, which was derived and tested in a cohort of pregnant participants in the UK (Model 1). This model comprises maternal factors with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor (PlGF). The model was further retrained with adjustments for analyzers used for biochemical testing (Model 2). Discrimination was assessed by area under the receiver operating characteristic curve (AUC). The Delong test was used to compare the AUC of Model 1, Model 2, and the Fetal Medicine Foundation (FMF) competing risk model. RESULTS: The predictive performance of Model 1 was significantly lower than that of the FMF competing risk model in the prediction of preterm pre-eclampsia (0.82, 95% confidence interval [CI] 0.77-0.87 vs. 0.86, 95% CI 0.811-0.91, P = 0.019), term pre-eclampsia (0.75, 95% CI 0.71-0.80 vs. 0.79, 95% CI 0.75-0.83, P = 0.006), and any pre-eclampsia (0.78, 95% CI 0.74-0.81 vs. 0.82, 95% CI 0.79-0.84, P < 0.001). Following the retraining of the data with adjustments for the PlGF analyzers, the performance of Model 2 for predicting preterm pre-eclampsia, term pre-eclampsia, and any pre-eclampsia was improved with the AUC values increased to 0.84 (95% CI 0.80-0.89), 0.77 (95% CI 0.73-0.81), and 0.80 (95% CI 0.76-0.83), respectively. There were no differences in AUCs between Model 2 and the FMF competing risk model in the prediction of preterm pre-eclampsia (P = 0.135) and term pre-eclampsia (P = 0.084). However, Model 2 was inferior to the FMF competing risk model in predicting any pre-eclampsia (P = 0.024). CONCLUSION: This study has demonstrated that following adjustment for the biochemical marker analyzers, the predictive performance of the AI+ML prediction model for pre-eclampsia in the first trimester was comparable to that of the FMF competing risk model in an Asian population.

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother-child pairs.

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother-child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.6 million mother-child pairs between 2001 and 2014 with follow-up until 2020. Children who were born to mothers with any type of diabetes during pregnancy had a higher risk of ADHD than unexposed children (pooled hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.08-1.24). Higher risks of ADHD were also observed for both GDM (pooled HR = 1.10, 95% CI = 1.04-1.17) and PGDM (pooled HR = 1.39, 95% CI = 1.25-1.55). However, siblings with discordant exposure to GDM in pregnancy had similar risks of ADHD (pooled HR = 1.05, 95% CI = 0.94-1.17), suggesting potential confounding by unmeasured, shared familial factors. Our findings indicate that there is a small-to-moderate association between MDM and ADHD, whereas the association between GDM and ADHD is unlikely to be causal. This finding contrast with previous studies, which reported substantially higher risk estimates, and underscores the need to reevaluate the precise roles of hyperglycemia and genetic factors in the relationship between MDM and ADHD.

The association between victimization and inflammation: A meta-analysis.

BACKGROUND: To meta-analyze the existing studies examining the association of childhood and adulthood victimization with inflammation and to explore the moderating variables that affect these relationships. METHODS: Relevant work published before 28th February 2021 was identified by searching five major databases. We analyzed the cross-sectional data extracted from cross-sectional and longitudinal studies using the random-effects model to estimate the correlation (r) as the pooled effect size and further conducted subgroup analyses and sensitivity analyses. RESULTS: A total of 37 articles finally met the inclusion criteria, including studies for C-reactive protein (CRP) (k = 23; NCRP = 11,780), interleukin-6 (IL-6) (k = 31; NIL-6 = 8943), and tumor necrosis factor-alpha (TNF-α) (k = 14; NTNF-α = 4125). Overall, victimization has a significantly positive association with inflammation, with a small effect size (r = 0.122). Specifically, effect sizes were the largest for TNF-a (r = 0.152), followed by IL-6 (r = 0.119), and CRP (r = 0.084). Additionally, the effect sizes for victimization against children were r = 0.145 (k = 6) for childhood victimization - childhood inflammation, and r = 0.139 (k = 27) for childhood victimization - adulthood inflammation, which appear to be larger than that of victimization against adults (r = 0.039; k = 2). LIMITATIONS: Only a small number of studies on adult victimization were included. In addition, we only analyzed the cross-sectional relationship and did not have sufficient data to compare different types of victimization and single vs. multiple victimizations. CONCLUSIONS: Victimization is associated with a heightened inflammatory response. As victimization against children may have a stronger effect than victimization against adults, prevention of victimization targeting the childhood period may be necessary. Studies with more robust methodologies (i.e., representative, longitudinal, and multi-country designs) are needed to confirm these findings and to unpack the underlying mechanisms.

Levothyroxine Treatment Among Pregnant Women and Risk of Seizure in Children: A Population-Based Cohort Study.

INTRODUCTION AND OBJECTIVE: The risk of seizure in offspring following prenatal exposure to levothyroxine is not well investigated. This study aimed to evaluate the association between levothyroxine treatment among pregnant women and the risk of seizure in their offspring. METHODS: This population-based cohort study included all pregnant women who delivered a live birth between January 2001 to January 2018, with a follow-up to December 2020, using data from the Hong Kong Clinical Data Analysis and Reporting System. Propensity score fine-stratification weighted hazard ratios (wHR) with 95% confidence intervals (CIs) were presented to assess the association between maternal levothyroxine use during pregnancy and seizures in children. RESULTS: Among 528,343 included mother-child pairs, 3044 children were prenatally exposed to levothyroxine at any time during the pregnancy period. A significantly increased risk of seizure was observed in children of the prenatally exposed group compared with the prenatally unexposed group (wHR 1.12, 95% CI 1.02-1.22). An increased risk of seizure was observed when comparing the prenatally exposed group with euthyroid mothers who had no history of thyroid-related diagnosis or prescriptions (wHR 1.12, 95% CI 1.02-1.23). However, no significant difference was observed between the prenatally exposed group and those previously exposed to levothyroxine but had stopped during pregnancy (wHR 0.97, 95% CI 0.66-1.44). No significant difference was observed in the sibling-matched analysis either (wHR 1.23, 95% CI 0.76-2.01). CONCLUSION: The observed increased risk of seizure in children born from mothers exposed to levothyroxine during pregnancy might be due to residual confounding by maternal thyroid disease. The findings support the current guidelines on the safe use of levothyroxine treatment during pregnancy.

Association between Childhood Exposure to Family Violence and Telomere Length: A Meta-Analysis.

The aims of this meta-analysis were to examine the association between childhood exposure to family violence and telomere length and the moderating variables that influence this association. Relevant works published on or before 1st September 2022 were identified through a search in five major databases in English and 19 articles (N = 18,977) finally met the inclusion criteria. A meta-analysis was conducted to compute the pooled effect size (correlation; r), and moderator analyses were performed using a random effects meta-analytic model. The studies yielded a significant inverse association between childhood exposure to family violence and telomere length, with a small effect size (r = -0.038, 95% CI [-0.070, -0.005], p = 0.025). Furthermore, the strength of this association was stronger in studies examining the co-occurrence of multiple types of violence than in those examining just one type (Q = 8.143, p = 0.004). These findings suggested that victims' telomere length may be negatively influenced by childhood exposure to family violence and that such impairment appears to be stronger for those who are exposed to multiple types of violence. Future studies are necessary to examine the moderating and mediating factors underlying the association between childhood exposure to family violence and telomere length.

Adequate Dietary Intake and Vitamin D Supplementation: A Study of Their Relative Importance in Determining Serum Vitamin D and Ferritin Concentrations during Pregnancy.

Vitamin D is essential for human health. However, it is not clear if vitamin D supplementation is necessary for all pregnant women. This study examines the relative importance of dietary patterns and vitamin D supplementation frequency in determining serum 25-hydroxyvitamin D (25(OH)D) and ferritin concentrations among pregnant women in Hong Kong, China. A total of 572 healthy women were recruited from antenatal clinics at 25-35 weeks pregnant. Participants completed an electronic version of the food frequency questionnaire and a web questionnaire on supplement use. Their blood samples were tested for serum 25(OH)D and ferritin. The associations of dietary patterns and vitamin D supplementation frequency with serum 25(OH)D and ferritin concentrations were analyzed using moderated hierarchical regression. Two dietary patterns were identified. The adequate dietary intake was characterized by the high probability of meeting recommended daily food group servings, whereas the inadequate dietary intake was characterized by inadequate consumption of vegetables, fruits, meat, fish, and eggs, or alternatives. The association between adequate dietary intake and serum ferritin concentrations was independent of vitamin D supplementation frequency (ß = 0.05, p = 0.035), but dietary patterns interacted with vitamin D supplementation frequency to determine serum 25(OH)D concentrations (ß = -13.22, p = 0.014). The current study presents evidence on the relative importance of dietary patterns and vitamin D supplementation in maintaining sufficient vitamin D and iron in pregnancy. Antenatal nutrition counselling services should be provided to pregnant women who show signs of inadequate dietary intake.

Changing Patterns of Intimate Partner Violence against Pregnant Women: A Three-Year Longitudinal Study.

Intimate partner violence (IPV) against pregnant women adversely impacts women's and infants' health. This study aims to provide longitudinal evidence regarding how pregnant women's exposure to IPV changes over time. Additionally, we examine the risk and protective factors associated with these changes. In total, 340 pregnant women were recruited from an antenatal clinic in Hong Kong. IPV experiences and health conditions were assessed at pregnancy and at both 4 weeks and 3 years after childbirth. The women also reported adverse childhood experiences (ACEs), their family support, and perceived partner involvement. We found IPV prevalence among the study sample decreased from 22.9% before pregnancy to 13.5% during pregnancy, 14.7% at 4 weeks after childbirth, and 11.8% at 3 years after childbirth. We further found three types of IPV: 11.8% of women had a violent relationship (VR) persistently over time from pregnancy to 3 years after childbirth, 20.6% experienced decreased IPV (DVR), and 67.6% reported a nonviolent relationship (NVR) throughout the study period. VRs were associated with more severe mental health problems and higher ACEs. Family support and partner involvement may be protective factors for decreased IPV. Our present findings highlight the importance of identifying different IPV types over time to provide targeted intervention to the most vulnerable groups.