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 (PE) in Asia. METHODS: Between 1st August 2019 and 28th February 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from ten regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular six-week intervals, one cluster was randomized to transit from non-intervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm PE using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm PE ≥ 1 in 100, received low-dose aspirin from <16 weeks until 36 weeks. RESULTS: Overall, 88.04% (42,897/48,725) of women agreed to undergo first-trimester screening for preterm PE. Among those identified as high-risk in the intervention phase, 82.39% (2,919/3,543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm PE between the intervention and non-intervention phases (adjusted odds ratio [aOR] 1.59; 95% confidence interval [CI] 0.91 to 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 PE (aOR 0.59; 95%CI 0.37 to 0.92). Additionally, it correlated with 54%, 55% and 64% reduction in the incidence of PE with delivery at <34 weeks (aOR 0.46; 95%CI 0.23 to 0.93), spontaneous preterm birth <34 weeks (aOR 0.45; 95%CI 0.22 to 0.92) and perinatal death (aOR 0.34; 95%CI 0.12 to 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 PE is not associated with a significant reduction in the incidence of preterm PE. However, low-dose aspirin effectively reduces the incidence of preterm PE by 41% among high-risk women. The screen-and-prevent strategy for preterm PE 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 PE on a global scale.

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.

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.

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.

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.

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.

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.

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.

Application of Prenatal Whole Exome Sequencing for Structural Congenital Anomalies-Experience from a Local Prenatal Diagnostic Laboratory.

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.

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.

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.

Effectiveness of pelvic floor muscle training alone or combined with either a novel biofeedback device or conventional biofeedback for improving stress urinary incontinence: A randomized controlled pilot trial.

PURPOSE: To (i) compare the acceptance of a newly developed, novel biofeedback device (PelviSense) with that of conventional biofeedback (CB) using an intravaginal probe for the treatment of stress urinary incontinence (SUI) in women, (ii) examine the feasibility and safety of using the PelviSense device as a pelvic floor muscle (PFM) training (PFMT) adjunct, and (iii) compare the PFMT adherence and effectiveness of CB, the PelviSense device, with PFMT alone for women with SUI. METHODS: An assessor-blinded, three-arm, randomized controlled pilot trial was conducted among 51 women with SUI. Women were randomly allocated to one of three study groups (PelviSense-assisted PFMT, CB-assisted PFMT, or PFMT alone [control]). Outcome measures included the International Consultation on Incontinence Questionnaire-Short Form, the 1-h pad test, and the Modified Oxford Scale. RESULTS: Participants in the PelviSense-assisted PFMT group expressed good device acceptance. PFMT adherence was greater in the PelviSense-assisted PFMT group than in the unassisted or CB-assisted PFMT groups. Between-groups analysis revealed significant effects on improved SUI symptoms, urine loss severity, and PFM strength for the PelviSense-assisted PFMT group compared with the CB-assisted and PFMT alone groups. CONCLUSIONS: The pilot trial results demonstrated moderate to high PFMT adherence in the PelviSense-assisted PFMT group and supported the safety of using the PelviSense device. The preliminary results of the pilot trial showed that PelviSense-assisted PFMT was more effective for reducing SUI symptoms among women than unassisted or CB-assisted PFMT. TRIAL REGISTRATION: This trial was registered in http://ClinicalTrials.gov (reference number: NCT04638348) before the recruitment of the first participant.

Implementation of Public Funded Genome Sequencing in Evaluation of Fetal Structural Anomalies.

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.

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.

A combination of electroacupuncture and auricular acupuncture for postoperative pain after abdominal surgery for gynaecological diseases: A randomized controlled trial.

BACKGROUND: Postoperative pain following laparotomy for gynaecological diseases is a common problem that requires effective management to ensure patient satisfaction and recovery. Despite the wide use of acupuncture for pain management, knowledge of its efficacy in managing postoperative pain is limited. Previous literature used either acupuncture or auricular acupuncture alone. However, the combined use of acupuncture and auricular acupuncture have not been studied yet. PURPOSE: This study examined the efficacy and feasibility of combined electroacupuncture and auricular acupuncture compared to a sham control in reducing pain during 5 days after a laparotomy for gynaecological diseases. This combined therapy was hypothesized to provide greater pain reduction than previous studies with less frequent treatment. STUDY DESIGN: Randomized sham-controlled, patient- and- assessor-blinded trial. METHODS: This trial recruited 72 patients scheduled for laparotomy in Hong Kong. Either acupuncture (n = 36) or non-invasive sham acupuncture (n = 36) was performed on the patients preoperatively (1 session) and postoperatively (once a day, up to 6 sessions). The primary outcome was pain at rest, measured using a numerical rating scale from postoperative days 0-5. Secondary outcomes such as analgesics consumption were also assessed. A data and safety monitoring board (DSMB) was established. RESULTS: All 72 randomized patients were included in the analysis. The acupuncture group had a smaller pain score at rest at 22 hrs (mean = 2.6) than the sham control group (mean = 4.0) (Post hoc intention to treat analysis, Linear regression, mean difference = -1.4, 95% confidence interval = [-0.2] -2.7, p = 0.029). No statistically significant between-group difference was found in other outcomes. No serious adverse event was observed. CONCLUSION: Perioperative acupuncture treatments are safe and feasible, but the efficacy of acupuncture is inconclusive.

Vitamin D concentrations during pregnancy and in cord blood: a systematic review and meta-analysis.

CONTEXT: Effect size estimates for the association between vitamin D concentrations in maternal blood during pregnancy and in cord blood vary widely across studies, but no meta-analysis has been conducted to ascertain this association. OBJECTIVE: The aim of this systematic review was to estimate the pooled effect size for the association between circulating 25-hydroxyvitamin D (25[OH]D) concentrations, a marker of vitamin D status, in maternal blood during pregnancy and in cord blood. DATA SOURCES: The PubMed, Embase, and Web of Science databases were searched from their inception to February 2021. DATA EXTRACTION: Following the application of prespecified inclusion and exclusion criteria, 94 articles were eligible for full-text review, which was conducted by 2 authors independently. A third author was consulted when necessary and consensus reached. In total, 26 articles, which comprised 30 studies and 6212 mother-infant dyads, were included. Methodological quality was assessed using a modified version of the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data. Correlation coefficient (r) values for the association between maternal serum 25(OH)D concentrations during pregnancy and in cord blood were extracted. DATA ANALYSIS: The r values were pooled using random-effects meta-analyses. Sensitivity and subgroup analyses were performed to investigate sources of heterogeneity. The pooled r for all studies was 0.72 (95%CI, 0.64-0.79), indicating high heterogeneity (I2 = 95%, P < 0.01). After influential and outlier studies were removed, the pooled r for 9 studies was 0.70 (95%CI, 0.66-0.74), which resulted in a substantial reduction in heterogeneity (I2 = 41%, P=0.10). CONCLUSION: The findings support a positive and large correlation between maternal vitamin D concentrations during pregnancy and vitamin D concentrations in cord blood. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42021273348.

Total 25(OH)D Concentration Moderates the Association between Caffeine Consumption and the Alkaline Phosphatase Level in Pregnant Women.

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 (ß = −0.24, p = 0.006), but not in those with insufficient vitamin D (ß = −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.

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.

Sonographic measurement of cervical length and head perineum distance before labor to predict time of delivery.

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.