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Abstract 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.

Abstract Aims Intimate partner violence (IPV) is a public health challenge negatively affecting victims’ health. Telomere length (TL), a marker for biological ageing, might be reflective of the mechanisms through which IPV leads to adverse health outcomes. The objective of the current study was to explore the association between IPV and leucocyte TL. Methods We conducted an analysis using a subset of the UK Biobank (N = 144 049). Physical, sexual and emotional IPV were reported by the participants. DNA was extracted from peripheral blood leukocytes. TL was assayed by quantitative polymerase chain reaction. We used multivariable linear regressions to test the associations between IPV and TL adjusted for age, sex, ethnicity, deprivation, education, as well as symptoms of depression and post-traumatic stress disorder in a sensitivity analysis. Results After adjusting for sociodemographic factors, any IPV was associated with 0.02-s.d. shorter TL (β = −0.02, 95% CI −0.04 to −0.01). Of the three types of IPV, physical violence had a marginally stronger association (β = −0.05, 95% CI −0.07 to −0.02) than the other two types. The associations of numbers of IPV and TL showed a dose–response pattern whereby those who experienced all three types of IPV types had the shortest TL (β = −0.07, 95% CI −0.12 to −0.03), followed by those who experienced two types (β = −0.04, 95% CI −0.07 to −0.01). Following additional adjustment for symptoms of depression and PTSD, the associations were slightly attenuated but the general trend by number of IPVs remained. Conclusions Victims of IPV, particularly those exposed to multiple types of IPVs, had shorter TL indicative of accelerated biological ageing. Given that all three types of IPV are linked to TL, clinical practitioners need to comprehensively identify all types of IPV and those who received multiple types. Further studies should explore the association of violence with changes in TL over time, as well as to which extent biological ageing is a mechanistic factor.

Abstract Mosaic variegated aneuploidy (MVA) is a rare genetic disorder caused by mutations in BUB1B, CEP57, or TRIP13. We describe the prenatal diagnosis, molecular characterization, and clinical management of a long‐lived patient with BUB1B‐related MVA.

Fetal structural congenital abnormalities (SCAs) complicate 2–3% of all pregnancies. Whole-exome sequencing (WES) has been increasingly adopted prenatally when karyotyping and chromosomal microarray do not yield a diagnosis. This is a retrospective cohort study of 104 fetuses with SCAs identified on antenatal ultrasound in Hong Kong, where whole exome sequencing is performed. Molecular diagnosis was obtained in 25 of the 104 fetuses (24%). The highest diagnostic rate was found in fetuses with multiple SCAs (29.2%), particularly those with involvement of the cardiac and musculoskeletal systems. Variants of uncertain significance were detected in 8 out of the 104 fetuses (7.7%). Our study shows the utility of WES in the prenatal setting, and the extended use of the technology would be recommended in addition to conventional genetic workup.

With the advancements in prenatal diagnostics, genome sequencing is now incorporated into clinical use to maximize the diagnostic yield following uninformative conventional tests (karyotype and chromosomal microarray analysis). Hong Kong started publicly funded prenatal genomic sequencing as a sequential test in the investigation of fetal structural anomalies in April 2021. The objective of the study was to evaluate the clinical performance and usefulness of this new service over one year. We established a web-based multidisciplinary team to facilitate case selection among the expert members. We retrospectively analyzed the fetal phenotypes, test results, turnaround time and clinical impact in the first 15 whole exome sequencing and 14 whole genome sequencing. Overall, the molecular diagnostic rate was 37.9% (11/29). De novo autosomal dominant disorders accounted for 72.7% (8/11), inherited autosomal recessive disorders for 18.2% (2/11), and inherited X-linked disorders for 9.1% (1/11). The median turnaround time for ongoing pregnancy was 19.5 days (range, 13–31 days). Our study showed an overall clinical impact of 55.2% (16/29), which influenced reproductive decision-making in four cases, guided perinatal management in two cases and helped future family planning in ten cases. In conclusion, our findings support the important role of genome sequencing services in the prenatal diagnosis of fetal structural anomalies in a population setting. It is important to adopt a multidisciplinary team approach to support the comprehensive genetic service.

Microcephaly and microphthalmia are both rare congenital abnormalities, while concurrently, these two are even rarer. The underlying etiology would be complex interplaying between heterogeneous genetic background and the environmental pathogens, particularly during critical periods of early tissue development. Here, we reported a prenatal case with microcephaly, microphthalmia, and bilateral cataracts detected by ultrasonography and confirmed by autopsy. Various routine infection-related tests and invasive genetic testing were negative. Whole genome sequencing of fetus and parents revealed OCLN gene defects may be associated with these multiple congenital abnormalities.

Abstract 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.

The evidence as to whether caffeine consumption is beneficial or harmful to human health has been mixed. This study aimed to examine the effect of 25-hydroxyvitamin D (25(OH)D) concentration on the association between caffeine consumption and mineral metabolism in pregnant women. This is a cross-sectional study involving pregnant women at their 25th to 35th gestational week recruited at antenatal clinics in the period of July 2019 to December 2020. Peripheral blood samples were collected to determine their total 25(OH)D, albumin, alkaline phosphatase (ALP), calcium, phosphate, and ferritin level in serum. Questionnaires on demographics and dietary intake were also administered. Among 181 pregnant women recruited (Average age = 32.9 years), 50 (27.6%) of them were found to be vitamin D insufficient (25(OH)D concentration < 75 nmol/L), and 131 (72.4%) were vitamin D sufficient (25(OH)D concentration ≥ 75 nmol/L). Adjusted regression models identified an association between higher caffeine intake and lower ALP level only among vitamin D-sufficient pregnant women (β = −0.24, p = 0.006), but not in those with insufficient vitamin D (β = −0.02, p = 0.912). The findings provide new insights into 25(OH)D concentration as a potential modifier of the health effects of caffeine consumption during pregnancy.

Introduction: Conservative management by leaving the placenta in situ for placenta accreta spectrum (PAS) disorders can preserve the uterus with reduced surgical complications. This study aims to review the outcomes of planned conservative management for PAS disorders between January 2013 and December 2021. Methods: The medical records of patients with clinically and/or histopathologically confirmed PAS disorders who underwent conservative management by leaving the placenta in situ between 1 January 2013 and 31 December 2021 at Kwong Wah Hospital, Hong Kong, were retrospectively reviewed. Uterine artery embolisation and various haemostatic methods were used to control bleeding. Results: A total of 17 patients with PAS disorders were conservatively treated by leaving the placenta in situ. Of these, 15 patients had major placenta praevia; 16 patients had a history of Caesarean delivery; and 10 patients presented with sonographic features of PAS disorders. Intraoperatively, eight patients had partial placenta left in situ, whereas five patients had the entire placenta left in situ. All patients had good maternal outcomes and recovery, except for four patients who had major complications during the immediate postpartum period. Two patients eventually required a hysterectomy. Conclusion: Planned conservative management for PAS disorders can achieve good clinical outcomes in a regional hospital with a multidisciplinary team. [ABSTRACT FROM AUTHOR]

Objectives: This was an observational study on cervical length and head perineum distance and the prediction of time of delivery. One-hundred and twenty-five nulliparous women with uncomplicated, term, singleton pregnancy were recruited when they presented to the labor ward with show or infrequent painful uterine contractions (less than three contractions in ten minutes on a 30 min cardiotocogram). Apart from digital vaginal examination to assess cervical length and dilatation, sonographic cervical length and head perineum distance were measured by two-dimensional ultrasound. We compared women who delivered within 72 h of presentation of labor symptoms, with women who did not. After excluding ten women whose labor was induced and delivered within 72 h of presentation, one hundred and fifteen women were included for final data analysis. Main findings: Forty-nine women (42.6%) delivered while sixty-six women (57.4%) remained undelivered at 72 h of presentation of symptoms of labor. There was no statistically significant difference between the two groups on age, presence of show, contractions, fetal head station and presentation and mode of delivery. For the group who had delivered within 72 h of presentation of labor symptoms, the mean sonographic cervical length was 1.87 cm ± 0.62 cm, while the head perineum distance was 6.01 cm ± 1.15 cm. For the other group, the mean sonographic cervical length was 2.10 cm ± 0.83 cm; head perineum distance was 6.03 cm ± 1.18 cm. There was no statistically significant difference between the groups for both sonographic cervical length (p = .90); and head perineum distance (p = .08). We also compared the cervical length measured by digital vaginal examination versus sonography. The median sonographic measurements were 1.47 cm, 2.11 cm and 2.79 cm at “1 cm,” “2 cm” and “3 cm” digital vaginal measurement, respectively. However, there was extensive overlap between digitally and sonographically measured cervical length. Prediction accuracy of cervical length and head perineum distance was poor. The area under curve (AUC) of receiver operating characteristic (ROC) curve were 0.433 for sonographic cervical length and 0.501 for HPD. Conclusion: Transperineal sonographical assessment of cervical length and head perineum distance before labor was not useful in predicting the time of delivery. However, it can be explored as an alternative assessment method when digital vaginal examination is not preferred. [ABSTRACT FROM AUTHOR]

Context: Previous studies suggested a potential link of maternal thyroid dysfunction with adverse neurocognitive outcomes and impaired development of internal organs in offspring.Objective: To review the association between maternal thyroid dysfunction and the risk of adverse outcomes in offspring.Data Sources: PubMed, EMBASE, and Cochrane Library.Study Selections: Eligible studies reported the association between maternal thyroid hormone function and the risk of adverse outcomes in their children.Data Extraction: Reviewers extracted data on study characteristics and results independently.Data Synthesis: Estimates were pooled and reported as odds ratio (OR) with 95% confidence interval (CI). I2 tests were applied to assess the heterogeneity across studies.Results: We identified 29 eligible articles and found an association between maternal hyperthyroidism and attention deficit hyperactivity disorder (ADHD) (OR: 1.18, 95% CI: 1.04-1.34, I2 = 0%) and epilepsy (OR: 1.19, 95% CI: 1.08-1.31, I2 = 0%) in offspring; as well as an association of maternal hypothyroidism with increased risk of ADHD (OR: 1.14, 95% CI: 1.03-1.26, I2 = 25%), autism spectrum disorder (OR: 1.41, 95% CI: 1.05-1.90, I2 = 63%), and epilepsy (OR: 1.21, 95% CI: 1.06-1.39, I2 = 0%) in offspring.Conclusion: Routine measurement and timely treatment on thyroid function should be considered for pregnant women. [ABSTRACT FROM AUTHOR]

We present four cases of confirmed spontaneous septostomy in monochorionic diamniotic twin pregnancy and one false positive case in a regional hospital in Hong Kong between 2011 and 2017. Three of the cases of spontaneous septostomy were detected antenatally. [ABSTRACT FROM AUTHOR]

Background Human placenta is a convenient resource for biomedical research, and has not yet been used for neurointerventional surgery research. Objective Our objective was to explore the feasibility of using human placenta to test various endovascular interventions and for training. Design 18 placentas soon after delivery were prepared for six pilot studies. (1) Study on anatomical similarity to human cerebral vessel. (2) Simulation of stent assisted coiling and flow diversion on an aneurysm model. (3) Simulation of intra-arterial thrombolysis. (4) Simulation of embolization of arteriovenous malformation with glues. (5) Simulation of mechanical thrombolysis and comparison of different devices. (6) Vascular model for training of neurointerventionalists. Results When the chorionic plate vessels were compared with the cerebral cortical vessels, similarities were found in vascular branch patterns, histological cross sections, and angiographic appearances. Due to the semitransparency of its vessel wall, performance of flow diverter and stent assisted coiling of an aneurysm could be visualized under direct microscopic observation. Similarly, timing of clot lysis and glue polymerization could be estimated. Endothelial change after thrombectomy could be assessed by histological methods. From these pilot studies, the placenta model could be adopted to simulate various clinical situations. It is also ideal for interventional radiology training. Conclusions It is feasible to adopt the human placenta as an ex vivo vascular model in neurointerventional surgery research due to the fact that its vessels resemble the brain vasculature. [ABSTRACT FROM AUTHOR]

This study examines correlates of in-law conflict with intimate partner violence (IPV) against pregnant women in a cohort of Chinese pregnant women who visited antenatal clinics in Hong Kong. This was a territory-wide, cross-sectional study of 3,245 pregnant women recruited from seven hospitals in Hong Kong. Participants were invited to complete the Chinese Abuse Assessment Screen and a demographic questionnaire. About 9% of the pregnant women reported having been abused by their partners in the preceding year. In-law conflict was the characteristic most significantly associated with preceding-year abuse against pregnant women, after controlling for covariates. Findings underscore the need to obtain information on in-law conflict as a risk factor for IPV. In-law conflict should be included in the assessment of risk for IPV. For the prevention of IPV, family-based intervention is needed to work with victims as well as in-laws. [ABSTRACT FROM AUTHOR]

Intimate partner violence is a public health problem with human and economic costs. Although there is a substantial body of literature regarding women's experiences in abusive intimate relationships, information about this kind of violence in the Chinese context is scarce. A review of the research on intimate partner violence in Chinese obstetric/gynecology patients has found 22 published papers representing 15 research studies conducted in Mainland China or Hong Kong. The majority of the studies focus on the prevalence of, and risk factors for, intimate partner violence in this group of women. Among the studies, variations in design, sample, definition of intimate partner violence and range of questions asked were noted. As no standardized instruments were used for the detection of intimate partner violence, a range of prevalence rates (e.g., 3.6-16.8% during pregnancy) and types of violence were reported, and it was difficult to draw meaningful comparisons across the studies. Despite the limitations, much can still be learned from the existing findings, especially in terms of the identification of risk factors in the Chinese context (e.g., in-law conflict and extramarital affairs). Such information could provide a useful basis for further investigation into the cultural context of violent experiences of Chinese women. [ABSTRACT FROM AUTHOR]

The purpose of the study was to shed light on the potentially differing dynamics of violence against separated and divorced women by their ex-husbands and violence against married women by their current husbands. Using a nationally representative sample of 7,369 heterosexual women from Cycle 13 of Statistics Canada's General Social Survey, available risk markers were examined in the context of a nested ecological framework. Separated women reported nine times the prevalence of violence and divorced women reported about four times the prevalence of violence compared with married women. The strongest predictors of violence against married women, namely, patriarchal domination, sexual jealousy, and possessiveness, were not significant predictors of violence against separated and divorced women. This suggested that post-separation violence is a complex phenomenon the dynamics of which can be affected by much more than domination and ownership. [ABSTRACT FROM AUTHOR]

The aim of this study is to explore the relationship between high cord blood thyroid-stimulating hormone (TSH) level and in-utero stress to the fetus in gestational diabetes mellitus (GDM). Cord blood TSH results were analyzed in 1,578 euthyroid infants from singleton pregnancies with GDM: 103 with elevated TSH (>16 mIU/l) and 1,475 with normal TSH. Maternal characteristics, pregnancy outcome and perinatal complications were compared between the two groups. Multiple logistic regression was used to study the association between high cord blood TSH level and various perinatal complications which reflect in-utero stress in GDM after adjusting for the confounding effects of parity, instrumental delivery, cesarean section and baby gender. High cord blood TSH level was found to be associated with the 1-min Apgar score <7 (OR 3.31, 95% CI 1.78–6.16), birth trauma (OR 3.44, 95% CI 1.11–10.69), neonatal jaundice requiring treatment (OR 2.08, 95% CI 1.30–3.32), neonatal sepsis (OR 2.34, 95% CI 1.24–4.42), respiratory complications (OR 3.45, 95% CI 1.37–8.70), neurological complications (OR 8.01, 95% CI 1.91–33.60) and overall perinatal morbidity (OR 2.41, 95% CI 1.58–3.67). Cord blood TSH level seems to be a better and independent indicator of the in-utero stress to the fetus in GDM when compared to the commonly used sugar profile result and HbA1c level. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (β = 0.05, p = 0.035), but dietary patterns interacted with vitamin D supplementation frequency to determine serum 25(OH)D concentrations (β = −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.