Search

ObjectiveTo assess the evidence of the association between exposure to intimate partner violence (IPV) and postpartum depression. IPV during pregnancy can have immediate and long-term physical and mental health consequences for the family. Therefore, it has been hypothesised that IPV may affect the risk of developing postpartum depression.MethodsA systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Global Health Library, Scopus and Google scholar were searched for published studies without restrictions on language, time or study design (up to May 2020). Studies were included if they assessed postpartum depression using the Edinburg Postnatal Depression Scale (cut-off≥10), among women who had been exposed to IPV (emotional, physical and/or sexual abuse). The quality of studies was judged according to the Newcastle-Ottawa scale.ResultsA total of 33 studies were included in the review (participants n=131 131). The majority of studies found an association between exposure to IPV and the development of signs of postpartum depression. Overall, studies measured both exposure and outcome in various ways and controlled for a vast number of different confounders. Thirty percent of the studies were set in low-income and lower-middle-income countries while the rest were set in upper-middle-income and high-income countries and the association did not differ across settings. Among the studies reporting adjusted OR (aOR) (n=26), the significant aOR ranged between 1.18 and 6.87 (95% CI 1.12 to 11.78). The majority of the studies were judged as ‘good quality’ (n=20/33).ConclusionWe found evidence of an association between exposure to IPV and the development of signs of postpartum depression. Meta-analysis or individual patient data meta-analysis is required to quantify the magnitude of the association between IPV and postpartum depression.PROSPERO registration numberCRD42020209435.

Objective To examine how (a) parity and (b) mode of birth were associated with later Quality of Life (QOL) in young adult women, with a mean follow-up of 11.0 years. Design Prospective cohort study Setting Australia r sample A total of 7770 women participating in the 1973–1978 cohort of the Longitudinal Study of Women’s Health. Methods Linear regression models were used to estimate (1) prospective associations between parity and mode of birth with eight subscale and two summary scores of the SF36, assessed after a mean follow-up of 11 years., and (2) differences between SF36 scores at follow up for women in different parity and mode of birth categories. Main outcome measure Quality of Life as measured by the SF36 Results Women experiencing no births (parity 0) and one birth (parity 1) had lower scores on all the physical health measures, and on some mental health measures, than women who had 2 births (parity 2) (all p Conclusions Parity and mode of birth may have long-term implications for women’s physical and mental health. Both childless and women with only one child had poorer physical and mental health than their peers with two children. Women with only caesarean section(s) also had poorer health than women who had vaginal birth/s.

ObjectiveThe objective of the present study was to assess the prevalence and type-specific distribution of cervical high-risk (HR) human papillomavirus (HPV) among women with normal and abnormal cytology, and to describe risk factors for HR HPV among HIV-positive and HIV-negative women in Tanzania.MethodologyA cross-sectional study was conducted in existing cervical cancer screening clinics in Kilimanjaro and Dar es Salaam. Cervical specimens were obtained from women aged 25–60 years. Samples were shipped to Denmark for cytological examination, and to Germany for HR HPV testing (using Hybrid Capture 2) and genotyping (using LiPaExtra). Risk factors associated with HPV were assessed by multivariable logistic regression analysis.ResultAltogether, 4080 women were recruited with 3416 women contributing data for the present paper, including 609 HIV-positive women and 2807 HIV-negative women. The overall HR HPV prevalence was 18.9%, whereas the HR HPV prevalence in women with high-grade squamous intraepithelial lesions (HSILs) was 92.7%. Among HPV-positive women with HSIL, HPV16 (32.5%) and HPV58 (19.3%) were the the most common types followed by HPV18 (16.7%) and HPV52 (16.7%). Factors associated with HR HPV included younger age, increasing number of partners and early age at first intercourse. Similar risk factors were found among HIV-positive and HIV-negative women. In addition, among HIV-positive women, those with CD4 counts 3 had an increased risk of HR HPV (OR 2.2; 95% CI 1.2 to 4.8) compared with individuals with CD4 count ≥500 cells/mm3.ConclusionGiven the HPV distribution among Tanzanian women, the current HPV vaccination in Tanzania using quadrivalent vaccine may be considered replaced by the nonavalent vaccine in the future. In addition, appropriate antiretroviral treatment management including monitoring of viremia may decrease the burden of HR HPV in HIV-positive women.

Purpose: We estimated the association between maternal antidepressant (AD) use in early pregnancy and risk of congenital heart defects. Methods: We applied a case-time-control design with the aim of controlling for confounding from time-invariant factors and compared the results of the design to results from a cohort design in a population of 792 685 singletons born alive in Denmark during 1995-2008. In the case-time-control design, we identified children diagnosed with a congenital heart defect in the first 5 years of life (cases) and compared maternal AD use in the risk period (the first 3 months of pregnancy) and the reference period (gestational months 5-7). A nondiseased control group was included to adjust for time trends of exposure. In the cohort design, we identified children whose mothers redeemed at least one AD prescription in the first 3 months of pregnancy (the exposed) and two other groups including the unexposed children with maternal AD prescriptions in the 12 months before pregnancy. We applied conditional logistic regression and logistic regression to compute odds ratios (ORs) and 95% confidence intervals (CIs). Results: The case-time-control OR for any congenital heart defect was 1.03 (95% CI, 0.61-1.73), which was similar to the OR (1.09, 95% CI, 0.88-1.35) from the cohort design when we compared the exposed children with the unexposed children with maternal AD use before pregnancy. Conclusions: The case-time-control design provided results similar to the cohort design when the cohort design had a better confounder control strategy. We discussed the strengths and drawbacks of case-time-control design.

INTRODUCTION: Human papillomavirus (HPV) is the causative agent of precancerous lesions and cervical cancer, cervical cancer being the leading cause of deaths in Tanzanian women. Early detection and treatment of precancerous lesions are important in the prevention of cervical cancer cases.MATERIAL AND METHODS: We conducted a cross-sectional study among 3390 Tanzanian women aged 25-60 years. Information on lifestyle habits was collected, and women underwent gynecological examination with collection of cervical cells for conventional cytological and HPV testing. Blood samples were tested for HIV. The association between cervical high-grade cytology (HGC) and potential risk factors was examined using multivariable logistic regression adjusting for age and high-risk HPV (HR-HPV).RESULTS: The prevalence of HGC was 3.6% and of low-grade cytology was 8.3%. In women who were both HR-HPV-positive and HIV-positive, the prevalence of HGC was 28.3%. It increased by age and was 47% among women aged 50-60 years. Women, who had their sexual debut at age 9-15 years and 16-18 years, respectively, had 2.5 and 2.4 times increased odds of HGC compared with women whose sexual debut was at age 21 years and older. HIV-positive women had increased odds of HGC in comparison with HIV-negative women after adjustment for age (odds ratio [OR] 2.95, 95% CI 1.92-4.54). HR-HPV-positive women had nearly 100-fold increased odds of HGC compared with HR-HPV-negative women (OR 96.6, 95% CI 48.0-194), and this estimate was higher among HIV-positive women (OR 152.2, 95% CI 36.1-642.0).CONCLUSIONS: Increasing age, early age at first intercourse, HR-HPV, and HIV infections were associated with a substantially increased risk of HGC.

PurposeCervical cancer is a major cause of death among women in Eastern Africa, and the distribution of human papillomavirus (HPV) according to HIV status is inadequately characterised in this region. In order to guide future cervical cancer preventive strategies that involve HPV testing, the Comprehensive Cervical Cancer Prevention in Tanzania (CONCEPT) study was established in 2015. The CONCEPT cohort aims to investigate the natural history of HPV and determine acquisition and persistence patterns of high-risk (HR) HPV among HIV-positive and HIV-negative women. Further, the influence of lifestyle and sexual/reproductive factors will be investigated. The main objective of this article is to describe how the CONCEPT cohort was established.ParticipantsWomen aged 25–60 years were enrolled from cervical cancer screening clinics in Dar-es-Salaam and Moshi, Tanzania. Data were collected at baseline, at 14 months (first follow-up) and at 28 months (second follow-up). Biological samples included two cervical swabs for careHPV DNA testing, cytology, Hybrid Capture 2, genotyping and blood samples for HIV. Visual inspection with acetic acid was performed, and sociodemographic, lifestyle and sexual/reproductive characteristics were collected through a standardised questionnaire.Findings to date4043 women were included in the cohort from August 2015 to May 2017. At baseline, 696 (17.1%) women were HR HPV positive, and among these, 31.6% were HIV positive; 139 women (3.4%) had high-grade squamous intraepithelial lesions. 3074 women (81%) attended the first follow-up. The majority attended after receiving a phone call reminder (35%) or from home via self-samples (41%). At first follow-up, 438 (14.4%) were HR HPV positive and 30.4% of these were HIV positive.Future plansA second follow-up is underway (17 December 2018–October 2020). We plan to integrate our data with a previous cross-sectional HPV study from Tanzania to increase the power of our findings. Researchers interested in collaborating are welcomed, either by extracting data or jointly requesting further investigation from the cohort.

BACKGROUND: Cortisol has been used to capture psychophysiological stress during childbirth and postpartum wellbeing. We explored the effect of a brief antenatal training course in self-hypnosis on salivary cortisol during childbirth and 6 weeks postpartum.METHODS: In a randomized, controlled trial conducted at Aarhus University Hospital Skejby Denmark during the period January 2010 until October 2010, a total of 349 healthy nulliparous women were included. They were randomly allocated to a hypnosis group (n = 136) receiving three one-hour lessons in self-hypnosis with additional audio-recordings, a relaxation group (n = 134) receiving three one-hour lessons in various relaxation methods with audio-recordings for additional training, and a usual care group (n = 79) receiving ordinary antenatal care only. Salivary cortisol samples were collected during childbirth (at the beginning of the pushing state, 30 minutes, and 2 hours after childbirth), and 6 weeks postpartum (at wake up, 30 minutes after wake up, and evening). Cortisol concentrations were compared using a linear mixed-effects model. Correlations between cortisol concentrations and length of birth, experienced pain and calmness during birth were examined by a Spearman rank correlation test.FINDINGS: During childbirth, week correlations were found between cortisol concentrations 30 minutes after childbirth and length of birth. In the beginning of the pushing state and 2 hours after childbirth, we found a tendency towards higher cortisol concentrations in the hypnosis group compared to the other two groups (hypnosis versus relaxation p = 0.02 and 0.03, hypnosis versus usual care p = 0.08 and 0.05). No differences were observed in cortisol concentrations between the groups 30 minutes after childbirth (hypnosis versus relaxation p = 0.08, hypnosis versus usual care 0.10) or 6 weeks postpartum (hypnosis versus relaxation: p = 0.85, 0.51, and 0.68, hypnosis versus usual care: p = 0.85, 0.93, and 0.96).CONCLUSION: Antenatal hypnosis training may increase the release of cortisol during childbirth with no long-term consequences. Further research is needed to help interpret these findings.

AimsThis study aimed to examine the feasibility of a web-based questionnaire when collecting information on alcohol consumption in pregnancy to identify women with risk drinking behaviour, and to describe factors associated with risk drinking behaviour, and the use of specialized care for prenatal risk drinking.MethodsIn 2413 women referred to antenatal care at Odense University Hospital, Denmark, April–October 2018, self-reported alcohol intake was retrieved from a web-based questionnaire. Replies were screened for risk drinking behaviour: current intake of ≥7 drinks/week, ≥3 binge drinking episodes (intake of ≥5 drinks on a single occasion) in pregnancy, binge drinking after recognition of pregnancy and/or a TWEAK-score ≥ 2 points. Women with risk drinking behaviour were called to clarify the need for specialized care. A summary of the interview was obtained from the medical records.ResultsOverall, 2168 (90%) completed the questionnaire. Of 2097 women providing information on alcohol intake, 77 (4%) had risk drinking behaviour. Risk drinking was associated with higher alcohol intake prior to pregnancy, spontaneous conception, younger age, nulliparity and higher level of physical activity in pregnancy. Amongst 47 women with risk drinking behaviour reached by phone, five (11%, 95% CI 4–23%) accepted examinations of the child by paediatrician and child psychologist, and ConclusionsA web-based questionnaire was feasible when collecting information on alcohol consumption in pregnancy to identify risk drinking behaviour. Women with risk drinking behaviour had a low acceptance of referral to specialized care.

BACKGROUND: Limited research has addressed whether maternal alcohol intake in early pregnancy increases the risk of spontaneous preterm birth. In the current study, we examined how alcohol binge drinking and weekly alcohol intake in early pregnancy were associated with spontaneous preterm birth in a contemporary cohort of Danish women.METHODS: We included 15,776 pregnancies of 14,894 women referred to antenatal care at Copenhagen University Hospital, Denmark, between 2012 and 2016. Self-reported alcohol intake in early pregnancy was obtained from a Web-based questionnaire completed prior to the women's first visit at the department. Information on spontaneous preterm birth was extracted from the Danish Medical Birth Register. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of spontaneous preterm birth according to self-reported alcohol binge drinking and weekly intake of alcohol in early pregnancy were derived from Cox regression.RESULTS: Women reporting 1, 2, and ≥ 3 binge drinking episodes had an aHR for spontaneous preterm birth of 0.88 (95% CI 0.68 to 1.14), 1.34 (95% CI 0.98 to 1.82), and 0.93 (95% CI 0.62 to 1.41), respectively, compared to women with no binge drinking episodes. Women who reported an intake of ≥ 1 drink per week on average had an aHR for spontaneous preterm birth of 1.09 (95% CI 0.63 to 1.89) compared to abstainers. When restricting to nulliparous women or cohabiting women with ≥ 3 years of higher education, this estimate was 1.28 (95% CI 0.69 to 2.40) and 1.20 (95% CI 0.67 to 2.15), respectively.CONCLUSION: We found no evidence that maternal alcohol intake in early pregnancy was associated with a higher risk of spontaneous preterm birth, neither for alcohol binge drinking nor for a low average weekly intake of alcohol.

Objective To evaluate the reduction of surgical site infections by prophylactic incisional negative pressure wound therapy compared with standard postoperative dressings in obese women giving birth by caesarean section. Design Multicentre randomised controlled trial. Setting Five hospitals in Denmark. Population Obese women (prepregnancy body mass index (BMI) ≥30 kg/m2) undergoing elective or emergency caesarean section. Method The participants were randomly assigned to incisional negative pressure wound therapy or a standard dressing after caesarean section and analysed by intention‐to‐treat. Blinding was not possible due to the nature of the intervention. Main outcome measures The primary outcome was surgical site infection requiring antibiotic treatment within the first 30 days after surgery. Secondary outcomes included wound exudate, dehiscence and health‐related quality of life. Results Incisional negative pressure wound therapy was applied to 432 women and 444 women had a standard dressing. Demographics were similar between groups. Surgical site infection occurred in 20 (4.6%) women treated with incisional negative pressure wound therapy and in 41 (9.2%) women treated with a standard dressing (relative risk 0.50, 95% CI 0.30–0.84; number needed to treat 22; P = 0.007). The effect remained statistically significant when adjusted for BMI and other potential risk factors. Incisional negative pressure wound therapy significantly reduced wound exudate whereas no difference was found for dehiscence and quality of life between the two groups. Conclusion Prophylactic use of incisional negative pressure wound therapy reduced the risk of surgical site infection in obese women giving birth by caesarean section. Tweetable abstract RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI., Tweetable abstract RCT: prophylactic incisional NPWT versus standard dressings postcaesarean in 876 women significantly reduces the risk of SSI.

BACKGROUND: There is a complex interaction between female and male sex hormones and the risk of epilepsy. Whether prenatal exposure to higher levels of sex hormones affects the development of epilepsy in childhood or later in life is not well known. The sex hormone environment of fetuses may be affected by the sex of the co-twin. We estimated the risk of epilepsy for twins with an opposite-sex (OS) co-twin compared with twins with a same-sex (SS) co-twin.METHODS: From the Danish Twin Registry, we identified OS female twins (n = 11,078), SS female twins (n = 19,186), OS male twins (n = 11,080), and SS male twins (n = 20,207) born between 1977 and 2009. The SS twins include monozygotic twins, dizygotic twins, and twins with unknown zygosity. These children were followed up from day 29 after birth until diagnosis of epilepsy, death, emigration, or end of follow-up (31 December 2011) whichever came first. Information on diagnosis of epilepsy was obtained from the Danish National Patient Registry. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for epilepsy in the OS twins using a Cox proportional hazards regression model compared with the SS twins. To account for the correlation of twins from the same mother when estimating standard errors, we used the cluster option in Stata.RESULTS: We identified 152 OS female twins, 282 SS female twins, 162 OS male twins, and 335 SS male twins diagnosed with epilepsy corresponding to an incidence rate of 9.9 and 9.7 per 10,000 person years for the OS and SS female twins, and 10.6 and 10.9 per 10,000 person years for the OS and SS male twins, respectively. We found a similar risk of epilepsy among the OS and SS female twins [HR = 1.01; 95% CI 0.83-1.24] as well as among the OS and SS male twins [HR = 0.94; 95% CI 0.78-1.14] CONCLUSIONS: In this population-based study of Danish twins, we did not find difference in the risk of epilepsy between twins with an OS co-twin and twins with a SS co-twin. This applied to both female and male twins. The study therefore does not support the hypothesis that subtle hormone difference in fetal life due to co-twin may play a role in the development of epilepsy later in life.

OBJECTIVE: To examine the test performance of careHPV, Hybrid Capture2 (HC2) and visual inspection with acetic acid (VIA) for detection of cytologically diagnosed high-grade cervical lesions or cancer (HSIL+).DESIGN: Cross-sectional study.SETTING: Ocean Road Cancer Institute (ORCI) and Kilimanjaro Christian Medical Center (KCMC), Tanzania.POPULATION: Women attending routine cervical cancer screening.METHOD: We enrolled 4080 women (25-60 years) in the study. The women were interviewed on lifestyle habits, and tested for HIV. A cervical specimen for careHPV testing (performed at ORCI and KCMC), and a liquid-based cytology sample for HPV DNA detection using HC2 (performed at Tuebingen University Hospital, Germany) and for cytology assessment (performed at Vejle Hospital, Denmark) were obtained at a gynecological examination. Subsequently, VIA was performed. With cytology as gold standard, the sensitivity and specificity of careHPV, HC2, and VIA for detection of HSIL+ were calculated.RESULTS: Altogether, 23.6% had a positive careHPV test, 19.1% had positive HC2 test, and 6.3% had a positive VIA test. The sensitivity/specificity was 88.9%/78.9% for careHPV and 91.1%/83.7%, for HC2. VIA showed a low sensitivity of 31.1% but a high specificity (94.6%) for detection of HSIL+. The sensitivity of careHPV, HC2 and VIA was higher among younger women, and among HIV positive women. VIA triage of careHPV positive women improved specificity, but sensitivity dropped to 27%.CONCLUSION: Our results confirm the low sensitivity of VIA for detection of HSIL+ and further document that careHPV test is promising as a primary screening method for cervical-cancer prevention in low-resource regions. A suitable triage test has to be identified.

ObjectiveThe objective of this study was to examine whether exposure to Intimate Partner Violence (IPV) is associated with premature termination of Exclusive Breastfeeding (EB). Per WHO recommendations, this was defined as ceasing breastfeeding or supplementing with other foods or liquids before the child was 6 months old.MethodIt is a prospective cohort study set in Moshi, Tanzania consisting of 1128 pregnant women with live singleton births. Women were enrolled during pregnancy and followed up with interviews during pregnancy, after birth and 2-3 years postpartum, using structured questionnaires. Emotional, physical and sexual IPV exerted by the current partner was assessed at 34 weeks gestational age with WHO questionnaires. Months of EB was assessed 2-3 years postpartum. Premature termination of EB was defined as less than 6 months of EB. Analyses were made using a logistic regression model adjusted for maternal age, education, HIV-status, alcohol use during pregnancy and parity. Confounding variables were determined using a theoretical framework approach, i.e. a Directed Acyclic Graph model to minimize bias.ResultsWomen who were exposed to IPV had more than 50% higher odds of terminating EB before the child was 6 months old compared to women who were not exposed (aOR = 1.62, 95%CI: 1.27-2.06). Women exposed to all three types of IPV had twice the odds of early termination of EB (aOR = 1.95, 1.12; 3.37). Furthermore, the odds were tripled if exposure happened specifically during the index pregnancy (aOR = 2.93 95%CI: 1.3; 6.6). Stratified analyses showed the most severely affected groups were the mothers older than 30 and those who gave birth to girls.ConclusionsThe results indicated that exposure to IPV is associated with increased risk of premature termination of EB. The odds increase with multiple types of the IPV, especially when exposed during the index pregnancy.

BACKGROUND: Little is known about maternal alcohol intake in early pregnancy and the risk of attention-deficit/hyperactivity disorder (ADHD) in children beyond 5 years of age. We examined the association between alcohol binge drinking and weekly alcohol intake in early pregnancy and the risk of ADHD in children followed from birth to 19 years of age.METHODS: We included 48,072 children born between 1998 and 2012, whose mothers participated in the Aarhus Birth Cohort. Maternal alcohol intake was obtained from a self-administered questionnaire completed in early pregnancy. ADHD diagnoses were retrieved from the Danish Psychiatric Central Research Register and the Danish National Patient Register. Crude hazard ratio and adjusted hazard ratio (aHR) of ADHD according to alcohol binge drinking or weekly intake of alcohol were calculated using the Cox regression.RESULTS: Compared to children of women with no binge drinking episodes, we observed an aHR for ADHD of 0.91 (95% CI 0.76 to 1.08), 0.73 (95% CI 0.56 to 0.96), and 0.77 (95% CI 0.57 to 1.06) among children of women reporting 1, 2, and 3 or more binge drinking episodes, respectively. Among children of women drinking CONCLUSION: We found no evidence that binge drinking or low alcohol intake in early pregnancy was associated with the risk of ADHD in children.

Objective To assess early recovery of physical health after robotic minimally invasive surgery (RMIS) for early-stage endometrial cancer using the European Organisation of Research and Treatment of Cancer Computer Adaptive Test Core questionnaire (EORTC CAT Core). The EORTC CAT Core provides individualised measurements while maintaining comparability. A hypothesis of individual complete recovery to baseline within three post-surgical weeks was evaluated. Methods Ninety-four women who underwent RMIS for early-stage endometrial cancer were included consecutively. The EORTC CAT Core was distributed before surgery and prospectively every week during the first post-operative month. Repeated measures models were fitted for each of the four domains (physical functioning, role function, fatigue, and pain) and tested for impact of age, ASA score, minor/major surgery, and the individual baseline scores (poorest, intermediate, best). Results Women with the lowest physical functioning, lowest role function, highest fatigue level, and highest pain level at baseline all recovered within three weeks. Women with the highest physical functioning, highest role function, lowest level of fatigue, and lowest level of pain at baseline did not reach their individual baselines within the first post-operative month but had the most favourable domain-scores three weeks post-operatively. Conclusion The individual woman's physical health baseline score is predictive for her postoperative recovery following RMIS for early-stage endometrial cancer. Women with the best physical health had the best postoperative functions and lowest level of symptoms; however their recovery to baseline was prolonged. Computer adaptive testing may be a valuable tool for individualised pre-operative information and supportive care during surveillance.

Objective: To evaluate the cost-effectiveness of incisional negative pressure wound therapy (iNPWT) in preventing surgical site infection in obese women after caesarean section. Design: A cost-effectiveness analysis conducted alongside a clinical trial. Setting: Five obstetric departments in Denmark. Population: Women with a pregestational body mass index (BMI) ≥30 kg/m 2 . Method: We used data from a randomised controlled trial of 876 obese women who underwent elective or emergency caesarean section and were subsequently treated with iNPWT (n = 432) or a standard dressing (n = 444). Costs were estimated using data from four Danish National Databases and analysed from a healthcare perspective with a time horizon of 3 months after birth. Main outcome measures: Cost-effectiveness based on incremental cost per surgical site infection avoided and per quality-adjusted life-year (QALY) gained. Results: The total healthcare costs per woman were €5793.60 for iNPWT and €5840.89 for standard dressings. Incisional NPWT was the dominant strategy because it was both less expensive and more effective; however, no statistically significant difference was found for costs or QALYs. At a willingness-to-pay threshold of €30,000, the probability of the intervention being cost-effective was 92.8%. A subgroup analysis stratifying by BMI shows that the cost saving of the intervention was mainly driven by the benefit to women with a pre-pregnancy BMI ≥35 kg/m 2 . Conclusion: Incisional NPWT appears to be cost saving compared with standard dressings but this finding is not statistically significant. The cost savings were primarily found in women with a pre-pregnancy BMI ≥35 kg/m 2 . Tweetable abstract: Prophylactic incisional NPWT reduces the risk of SSI after caesarean section and is probably dominant compared with standard dressings #healtheconomics.

Importance: Minimally invasive laparoscopic surgery (MILS) for endometrial cancer reduces surgical morbidity compared with a total abdominal hysterectomy. However, only a minority of women with early-stage endometrial cancer undergo MILS. Objective: To evaluate the association between the Danish nationwide introduction of minimally invasive robotic surgery (MIRS) and severe complications in patients with early-stage endometrial cancer. Design, Setting, and Participants: In this nationwide prospective cohort study of 5654 women with early-stage endometrial cancer who had undergone surgery during the period from January 1, 2005, to June 30, 2015, data from the Danish Gynecological Cancer Database were linked with national registers on socioeconomic status, deaths, hospital diagnoses, and hospital treatments. The women were divided into 2 groups; group 1 underwent surgery before the introduction of MIRS in their region, and group 2 underwent surgery after the introduction of MIRS. Women with an unknown disease stage, an unknown association with MIRS implementation, unknown histologic findings, sarcoma, or synchronous cancer were excluded, as were women who underwent vaginal or an unknown surgical type of hysterectomy. Statistical analysis was conducted from February 2, 2017, to May 4, 2018. Exposure: Minimally invasive robotic surgery, MILS, or total abdominal hysterectomy. Main Outcomes and Measures: Severe complications were dichotomized and encompassed death within 30 days after surgery and intraoperative and postoperative complications diagnosed within 90 days after surgery. Results: A total of 3091 women (mean [SD] age, 67 [10] years) were allocated to group 1, and a total of 2563 women (mean [SD] age, 68 [10] years) were allocated to group 2. In multivariate logistic regression analyses, the odds of severe complications were significantly higher in group 1 than in group 2 (odds ratio [OR], 1.39; 95% CI, 1.11-1.74). The proportion of women undergoing MILS was 14.1% (n = 436) in group 1 and 22.2% in group 2 (n = 569). The proportion of women undergoing MIRS in group 2 was 50.0% (n = 1282). In group 2, multivariate logistic regression analyses demonstrated that a total abdominal hysterectomy was associated with increased odds of severe complications compared with MILS (OR, 2.58; 95% CI, 1.80-3.70) and MIRS (OR, 3.87; 95% CI, 2.52-5.93). No difference was found for MILS compared with MIRS (OR, 1.50; 95% CI, 0.99-2.27). Conclusions and Relevance: The national introduction of MIRS changed the surgical approach for early-stage endometrial cancer from open surgery to minimally invasive surgery. This change in surgical approach was associated with a significantly reduced risk of severe complications.

Maternal obesity is associated with impaired fetal and neonatal survival, but underlying mechanisms are poorly understood. We examined how prepregnancy BMI and early gestational weight gain (GWG) were associated with cause-specific stillbirth and neonatal death. In 85,822 pregnancies in the Danish National Birth Cohort (1996–2002), we identified causes of death from medical records for 272 late stillbirths and 228 neonatal deaths. Prepregnancy BMI and early GWG derived from an early pregnancy interview and Cox regression were used to estimate associations with stillbirth or neonatal death as a combined outcome and nine specific cause-of-death categories. Compared to women with normal weight, risk of stillbirth or neonatal death was increased by 66% with overweight and 78% with obesity. Especially deaths due to placental dysfunction, umbilical cord complications, intrapartum events, and infections were increased in women with obesity. More stillbirths and neonatal deaths were observed in women with BMI &lt, 25 and low GWG. Additionally, unexplained intrauterine death was increased with low GWG, while more early stillbirths were seen with both low and high GWG. In conclusion, causes of death that relate to vascular and metabolic disturbances were increased in women with obesity. Low early GWG in women of normal weight deserves more clinical attention.

OBJECTIVE: To assess the influence of parental rheumatoid arthritis (RA) on risk of epilepsy.METHODS: We performed a nationwide cohort study including all singletons born in Denmark from 1977 to 2008 (n = 1,917,723) through individual linkage to nationwide Danish registries. The children were followed for an average of 16 years. Main outcome measures were adjusted hazard ratios (HRs) for epilepsy with onset in early childhood (29 days-4 years), late childhood (5-15 years), adolescence/adulthood (≥15 years), and at any age until the end of follow-up (December 31, 2010).RESULTS: Compared to unexposed children, children exposed to maternal RA had an increased risk of early and late childhood epilepsy (adjusted HRs 1.34 [95% confidence interval (CI) 1.13-1.60] and 1.26 [95% CI 1.13-1.41]), while children exposed to maternal RA had no increased risk of epilepsy in adolescence/adulthood (HR 1.15 [95% CI 0.92-1.45]). Paternal RA was not associated with an overall risk of epilepsy in the offspring (HR 0.96 [95% CI 0.81-1.15]) or at any age. Children exposed to maternal RA in utero had a more pronounced increased risk of early childhood epilepsy than children exposed to mothers who were diagnosed with RA after childbirth (HR 1.90 [95% CI 1.26-2.86] vs HR 1.26 [95% CI 1.03-1.52], respectively [p = 0.16]).CONCLUSIONS: Exposure to maternal RA was associated with an increased risk of childhood epilepsy, while exposure to paternal RA was not, which indicates that changes in the intrauterine environment may play a role. OBJECTIVE: To assess the influence of parental rheumatoid arthritis (RA) on risk of epilepsy.METHODS: We performed a nationwide cohort study including all singletons born in Denmark from 1977 to 2008 (n = 1,917,723) through individual linkage to nationwide Danish registries. The children were followed for an average of 16 years. Main outcome measures were adjusted hazard ratios (HRs) for epilepsy with onset in early childhood (29 days-4 years), late childhood (5-15 years), adolescence/adulthood (≥15 years), and at any age until the end of follow-up (December 31, 2010).RESULTS: Compared to unexposed children, children exposed to maternal RA had an increased risk of early and late childhood epilepsy (adjusted HRs 1.34 [95% confidence interval (CI) 1.13-1.60] and 1.26 [95% CI 1.13-1.41]), while children exposed to maternal RA had no increased risk of epilepsy in adolescence/adulthood (HR 1.15 [95% CI 0.92-1.45]). Paternal RA was not associated with an overall risk of epilepsy in the offspring (HR 0.96 [95% CI 0.81-1.15]) or at any age. Children exposed to maternal RA in utero had a more pronounced increased risk of early childhood epilepsy than children exposed to mothers who were diagnosed with RA after childbirth (HR 1.90 [95% CI 1.26-2.86] vs HR 1.26 [95% CI 1.03-1.52], respectively [p = 0.16]).CONCLUSIONS: Exposure to maternal RA was associated with an increased risk of childhood epilepsy, while exposure to paternal RA was not, which indicates that changes in the intrauterine environment may play a role.

An increased amount of DNA fragmentation in the spermatozoa (SDF) is linked to male infertility. The Sperm Chromatin Structure Assay (SCSA) is widely used for analysis of SDF. However, the current software (SCSASoft®) linked to this assay is licensed and often located within larger diagnostic centers. In this study, we present a protocol for using other types of software than SCSASoft® to determine the SDF index (DFI) with clinical relevance. This protocol is engineered after collecting and analyzing 254 samples from fertility patients and sperm donors over a 15-month period. DFI is analyzed using a strict protocol where the spermatozoa are treated with a strong acid (pH 1.2) followed by acridine orange. DFI is determined by a standard flow cytometric software, FACSDiva 6.1.3. Analysis of the outcome of the fertility treatment is included for 137 patients receiving either intrauterine inseminations (IUI) or timed coitus (TC). The results show that the chance of pregnancy declines as DFI increases. We also found that the male DFI affects the chance of pregnancy independent of the female age. We have shown that a standard flow cytometric software can be used when determining a clinical relevant DFI. These findings are a significant step toward implementing the analysis as a part of the routine, in-house diagnosing of the male fertility patient and subsequently optimizing the treatment course of the couple with reduced human and financial costs.

Background: The early life microbiome contributes to immune development. Antibiotics during pregnancy alter the microbiome and may influence disease risks in the offspring. We investigated the relationship between maternal antibiotic exposure before and during pregnancy, and risk of childhood hospitalization with infection.Methods: We used population-based Danish national databases for pregnancies between 1995 and 2009. Infants were followed from birth until their first infection-related hospitalization, death, 14th birthday, emigration or end-2009. Exposure was maternal antibiotics prescribed before and during pregnancy. Outcome was infection-related hospitalization.Results: 141 359 (18%) mothers had at least one antibiotic prescription during pregnancy, 230 886 (29.4% of those with complete data) in the 18 months before pregnancy. Of 776 657 live-born singletons, 443 546 infection-related hospitalizations occurred in 222 524 (28.6%) children. Pregnancy antibiotic exposure was associated with increased risk of childhood infection-related hospitalization [hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.17-1.19]. In mothers prescribed antibiotics only during pregnancy whose child did not receive pre-hospitalization antibiotics, this association was present only in those born vaginally. Higher risks of infection-related hospitalization occurred when pregnancy antibiotic prescriptions were closer to birth and in mothers receiving more pregnancy antibiotics. Children born to mothers exposed to antibiotics before (but not during) pregnancy also had increased risk of infection-related hospitalization (HR 1.10, 95% CI 1.07-1.12).Conclusions: Antibiotic exposure before or during pregnancy was associated with increased risk of childhood hospitalized infections. Alteration of the maternally derived microbiome and shared heritable and environmental determinants are possible contributory mechanisms.

BACKGROUND: Previous studies have shown an association between prepregnancy BMI and postpartum depression, but little is known about this association beyond one year postpartum and the influence of postpartum weight retention (PPWR).METHODS: We used data from 70355 mothers from the Danish National Birth Cohort to estimate the associations between maternal prepregnancy BMI and PPWR, respectively, and incident depression/anxiety disorders until six years postpartum. Outcome was depression or anxiety diagnosed clinically or filling a prescription for an antidepressant. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Follow-up started at the day of delivery. For the analysis regarding PPWR, follow-up started six months postpartum.RESULTS: Underweight, overweight and obesity were associated with depression and/or anxiety disorders when compared to normal-weight, though the associations were attenuated after adjustments (HR 1.24 [95% CI 1.06-1.45], 1.05 [95% CI 0.96-1.15] and 1.07 [95% CI 0.95-1.21] for underweight, overweight and obese, respectively). Compared to mothers who had returned to their prepregnancy BMI, risk of depression/anxiety disorders was increased for mothers, who from prepregnancy to 6 months postpartum experienced either weight loss >1 BMI unit (HR 1.19 [95% CI 1.06-1.25]), weight gain of 2-3 BMI units (HR 1.23 [95% CI 1.08-1.40]), or weight gain of ≥3 BMI units (HR 1.21 [95% CI 1.05-1.40]).LIMITATION: Causal direction and mechanisms behind the associations are largely unknown.CONCLUSIONS: Low prepregnancy body weight and postpartum weight gain or loss are associated with occurrence of depression and anxiety disorders.

BACKGROUND CONTEXT: Choosing the best surgical treatment for patients with spinal metastases remains a significant challenge for spine surgeons. There is currently no gold standard for surgical treatments. The Aarhus Spinal Metastases Algorithm (ASMA) was established to help surgeons choose the most appropriate surgical intervention for patients with spinal metastases.PURPOSE: The purpose of this study was to evaluate the clinical outcome of stratified surgical interventions based on the ASMA, which combines life expectancy and the anatomical classification of patients with spinal metastases to inform surgical decision making.STUDY DESIGN/SETTING: This is a retrospective study based on a prospective database.PATIENT SAMPLE: A consecutive series of 515 spinal metastatic patients who underwent surgically treatment from December 1992 to June 2012 in Aarhus University Hospital were included prospectively and analyzed in detail retrospectively.OUTCOME MEASURES: Survival time after surgery was determined for all patients. Neurological function was assessed using the Frankel score preoperatively and postoperatively (at the time of discharge). Complete outcome data were retrieved in 97.5% of this cohort.METHODS: Patients with spinal metastases were identified from an institutional database that prospectively collected data since 1992. Survival status data were obtained from a national registry. Neurological function was determined from the same institutional database or local Electronic Patient Journal system. Surgeons evaluated and classified patients into five surgical groups preoperatively by using the revised Tokuhashi score (TS) and the Tomita anatomical classification (TC).RESULTS: The overall median survival time of the cohort was 6.8 (95% confidence interval: 6.1-7.9) months. The median survival times in the five surgical groups determined by the ASMA were 2.1 (TS 0-4, TC 1-7), 5.1 (TS 5-8, TC 1-7), 12.1 (TS 9-11, TC 1-7 or TS 12-15, TC 7), 26.0 (TS 12-15, TC 4-6), and 36.0 (TS 12-15, TC 1-3) months. The 30-day mortality rate was 7.5%. Postoperative neurological function was maintained or improved in 469 patients (92.3%). Overall reoperation rate was 13.5%, commonly because of postoperative hematoma and new limb weakness.CONCLUSIONS: The ASMA recommends at least two surgical options for a particular patient by determining the preoperative life expectancy and anatomical classification of the spinal metastases. This algorithm could help spine surgeons to discriminate the risks of surgeries. The ASMA provides a tool to guild surgeons to evaluate the spinal metastases patients, select potential optimal surgery, and avoid life-threatening risks.

Childhood and adulthood exposure to passive smoking associated with increased risk of lung cancerhttp://ow.ly/7kXN30f6aZu

AIM: Although birth asphyxia is a major risk factor for neonatal and childhood morbidity and mortality, it has not been investigated much in relation to attention deficit hyperactivity disorder (ADHD). We examined whether birth asphyxia measured by the pH of the blood in the umbilical artery cord was associated with childhood ADHD.METHOD: A population-based cohort of 295 687 children born in Finland between 1991 and 2002 was followed until December 31, 2007. ADHD was identified by the International Classification of Diseases, 10th edition, as a diagnosis of hyperkinetic disorder. We examined the risk of ADHD with varying pH values using Cox regression, taking time trends into consideration.RESULTS: When compared to the reference group, a pH value below 7.10 was significantly associated with an increased risk of ADHD. The strongest risks were observed among children with a pH value CONCLUSION: Birth asphyxia, defined by low pH value, may predict an increased risk of ADHD in childhood. The association between the pH value and ADHD was homogenous when stratified by gestational age and the Apgar score.

Background: Previous prospective studies have shown inconsistent associations between serum 25-hydroxyvitamin D [25(OH)D] level and lung cancer incidence. The aim of the present study was to explore the associations of serum 25(OH)D levels with incidence of lung cancer overall and different histologic types. Methods: We performed a population-based prospective case-cohort study including 696 incident lung cancer cases and 5804 individuals in a subcohort who participated in the second survey of the Nord-Trøndelag Health Study in Norway. Cox proportional hazards regression models counting for the case-cohort design were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for lung cancer overall or histologic types in relation to serum 25(OH)D levels. Results: Compared with the 4th season-specific quartile of 25(OH)D (median 68.0 nmol/L), lower 25(OH)D levels were not associated with the incidence of overall, small or squamous cell lung cancer. However, the risk of adenocarcinoma was lower in the 2nd and 3rd quartiles (median 39.9 and 51.5 nmol/L) compared with the 4th quartile, with HRs of 0.63 (95% CI 0.41 to 0.98) and 0.58 (0.38 to 0.88), respectively. The associations of lower levels of 25(OH)D with a reduced risk of adenocarcinoma were only observed in the overweight/obese subjects [HRs for 2nd and 3rd quartiles: 0.40 (0.22 to 0.72) and 0.50 (0.27 to 0.92)] but not in the normal weight subjects [HRs: 0.95 (0.52 to 1.75) and 0.60 (0.32 to 1.10)]. Conclusions: Serum 25(OH)D levels were not associated with the risk of lung cancer in general. The observation that lower 25(OH)D levels were associated with a lower risk of adenocarcinoma should be interpreted with caution. This is a pre-print of an article published in [European Journal of Epidemiology]. The final authenticated version is available online at: https://doi.org/10.1007/s10654-017-0324-1

Background: Propylthiouracil (PTU) used in the treatment of maternal hyperthyroidism in early pregnancy may be associated with a higher prevalence of birth defects in the face and neck region and in the urinary system but the severity of these complications remains to be elucidated. Methods: Review of hospital-registered cases of birth defects in the face and neck region and in the urinary system after PTU exposure in early pregnancy. We obtained information on maternal redeemed prescription of PTU and child diagnosis of birth defect from nationwide registers for all children born in Denmark between 1996 and 2008 (n=817,093). The children were followed until December 31, 2010 (median age, 8.3 years) and the Cox proportional hazards model was used to estimate adjusted hazard ratio (HR) with 95% confidence interval (CI) for having a birth defect after PTU exposure versus nonexposed children (n=811,730). Results: Fourteen cases of birth defects were identified in the face and neck region and in the urinary system after PTU exposure in early pregnancy; 11 children were exposed to PTU only (n=564), whereas 3 children were born to mothers who switched from methimazole (MMI)/carbimazole (CMZ) to PTU in early pregnancy (n=159). Among children exposed to PTU only, the adjusted HR for having a birth defect in the face and neck region was 4.92 (95% CI 2.04–11.86) and in the urinary system 2.73 (1.22–6.07). Looking into details of the 14 cases, 7 children were diagnosed with a birth defect in the face and neck region (preauricular and branchial sinus/fistula/cyst) and 7 children had a birth defect in the urinary system (single cyst of kidney and hydronephrosis). Surgical treatment was registered in 6 of the cases with a birth defect in the face and neck region and 3 of the cases with a birth defect in the urinary system. Two of the children with a birth defect in the urinary system also had other birth defects (genital organs). Conclusions: We report details on possible PTU-associated birth defects. They tend to be less severe than the defects observed after MMI/CMZ exposure. Yet, the majority of affected children had to undergo surgery.

Study design We conducted a retrospective cohort study of 151 patients with breast cancer spinal metastases. Objective To investigate the influence of breast cancer subtypes on survival duration of patients with breast cancer spinal metastases, and to aid spine surgeons in selecting treatments on a more precise basis. Summary of background data There is lack of knowledge about specific prognosis of patients with spinal metastases in various breast cancer subtypes. Estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (Her-2) status are the key factors in determining breast cancer subtypes and predicting patients' response to adjuvant treatments. Methods Until August 2013, we retrieved 151 surgically treated patients with breast cancer spinal metastases and followed up all the patients for at least 2 years. Survival duration analysis and Cox proportional hazards regression model unadjusted and adjusted by age were used. Results Patients with ER-negative (-) breast cancer had 11 months shorter median survival duration (10.6 vs. 21.5 mo) and 48% higher mortality risk (P=0.03) than those with ER-positive (+) breast cancer. Patients with PgR (-) status had 59% higher mortality risk than those with PgR (+) status (P=0.02). Hormone receptor (HR) status is a combination of ER and PgR status. Patients with HR (-) status had an 11-month shorter median survival duration and 52% higher mortality risk (P=0.01) than patients with HR (+) status. Human epidermal growth factor receptor 2 subtypes had similar median survival duration and mortality risk. Patients with triple-negative breast cancer had a median survival duration of only 9.9 months. Conclusion Patients with spinal metastases with ER/HR (-) status and triple-negative breast cancer could be downgraded from score "5" to "3" in Tokuhashi scoring system and from "slow growth" to "moderate growth" in Tomita scoring system. Spine surgeons should be critical before performing high-risk extensive surgery in patients with ER/HR (-) status, and especially, in those with triple-negative status. Level of evidence 3.

Objective To examine the association between maternal hyper- and hypothyroidism and the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in the child. Design A population-based cohort study. Setting Singletons liveborn in Denmark between 1991 and 2004. Population A total of 857 014 singletons alive and living in Denmark at the age of 3 years. Methods Information on the diagnosis and/or treatment of maternal thyroid disease and the neurodevelopmental disorders ADHD and ASD in the child was obtained from Danish nationwide registers. The Cox proportional hazards model was used to estimate the hazard ratio (HR) with 95% confidence interval (95% CI) for risk of ADHD and ASD in children born to mothers with thyroid dysfunction, adjusting for potential confounding factors. Main outcome measures ADHD and ASD in the child. Results Altogether, 30 295 singletons (3.5%) were born to mothers with thyroid dysfunction. Maternal hyperthyroidism diagnosed and treated for the first time after the birth of the child increased the risk of ADHD in the child (adjusted HR 1.23; 95% CI 1.05–1.44), whereas hypothyroidism increased the risk of ASD (adjusted HR 1.34; 95% CI 1.14–1.59). No significant association was seen for maternal diagnosis and treatment prior to the birth of the child. Conclusions Children born to mothers diagnosed and treated for the first time for thyroid dysfunction after their birth may have been exposed to abnormal levels of maternal thyroid hormone already present during the pregnancy, and this untreated condition could increase the risk of specific neurodevelopmental disorders in the child.

BACKGROUND: Intimate partner violence (IPV) is a global problem that affects one-third of all women. The present study aims to develop and determine the validity of a screening instrument for the detection of IPV in pregnant women in Tanzania and Vietnam and to determine the minimum number of questions needed to identify IPV.METHOD: An IPV screening instrument based on eight questions was tested on 1,116 Tanzanian and 1,309 Vietnamese women who attended antenatal care before 24 gestational weeks. The women were re-interviewed during their 30th-34th gestational week where the World Health Organization (WHO) IPV questionnaire was used as the gold standard. In all, 255 combinations of eight different questions were first tested on the Tanzanian study population where sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. In the evaluation of the performance of the question combinations, different IPV types and the frequency of abusive acts were considered. The question combinations that performed best in Tanzania were subsequently evaluated in the Vietnamese study population.RESULTS: In Tanzania, a combination of three selected questions including one question on emotional IPV, one on physical IPV and one on sexual IPV was found to be most effective in identifying women who are exposed to at least one type of IPV during pregnancy (sensitivity = .80; specificity = .74). The performance of the identified combination was slightly less effective in Vietnam (sensitivity = .74; specificity = .68). Focusing on different IPV types, the best performance was found for exposure to physical IPV in both Tanzania (sensitivity = .93; specificity = .70) and Vietnam (sensitivity = .96; specificity = .55). In both countries, the sensitivity increased with the frequency of abuse whereas the specificity decreased.CONCLUSION: By asking pregnant women three simple questions we were able to identify women who were exposed to IPV during pregnancy in two different countries. The question combination performed best in assessing physical IPV where it identified 93% and 96% of Vietnamese and Tanzanian women, respectively, who were exposed to physical IPV.

Purpose Cancer and birth defects cluster in families more often than expected by chance, but the reasons are neither well known nor well studied. Methods From singletons born alive in Denmark between 1 January 1977 and 31 December 2007, we identified children who had no congenital malformations but had a full or half sibling with a congenital malformation (CM) diagnosed in the first year of life; this constituted the exposed group, while children whose siblings had no such condition constituted a reference group. We estimated cancer risks for children who had a full sibling or a half sibling with a CM using a Cox proportional hazards regression model. To control for confounding related to change of family structure, we estimated cancer risks for children from core families and children from broken families separately. Children were followed from birth up to 30 years of age (median follow-up 13.6 years). We obtained information on CMs and cancer from the Danish National Hospital Register and the Danish Cancer Registry. Results We identified 991,454 (78%) children from core families with 53,995 children who had a full sibling with a CM and 277,773 (22%) children from broken families with 7200 children who had a full sibling with a CM and 6194 children who had a half sibling with a CM. Children who had a full sibling with a CM from both core and broken families showed, in general, no increased cancer risk compared with children whose siblings had no CM, except in the case of children who had a full sibling with a CM in the nervous system (HR = 2.61, 95%CI:1.60–4.27) or in the eye, ear, face, or neck (HR = 2.47, 95%CI: 1.46–4.18). Children who had a half sibling with a CM seemed to have a higher cancer risk in early adulthood (HR = 1.87, 95%CI: 0.98–3.56). Conclusions Children who had a full sibling with a CM had no increased risk of cancer except for those who had a full sibling with a CM in the nervous system or in the eye, ear, face or neck. Children with a half-sibling with a CM tended to have an increased cancer risk in early adulthood, perhaps a result of chance. This study should be replicated using other data sources.

STUDY DESIGN.: A risk factor analysis study. OBJECTIVE.: To identify the causative factors for postoperative trunk shift in Lenke 1C scoliosis and investigate how to prevent it. SUMMARY OF BACKGROUND DATA.: When selective thoracic fusion is performed, postoperative trunk shift is a significant problem in the management of Lenke 1C scoliosis. It is often accompanied by unsatisfactory clinical outcomes and a risk of reoperation. METHODS.: We reviewed all the patients with adolescent idiopathic scoliosis (AIS) surgically treated in our institution from 2002 through 2008. Inclusion criteria were as follows: (1) patients with Lenke 1C curves who were treated with selective thoracic fusion using posterior pedicle screw-only constructs; (2) the lowest instrumented vertebra (LIV) ending at L1 level or above; and (3) 2-year radiographical follow-up. Eighteen radiographical parameters were chosen as potential risk factors. The 18 parameters measured (1) amount of correction obtained by surgery; (2) preoperative position of LIV; (3) magnitude of major thoracic and thoracolumbar/lumbar (MT and TL/L) curves and ratio of MT: TL/L curve; and (4) curve flexibility. Both comparative and correlation analyses were performed. Those parameters that had shown highest correlation with the 2-year thoracic apical vertebra-center sacral vertical line (AV-CSVL) distance were selected to form a linear regression model, by which the correlations were quantified. RESULTS.: Of the 278 patients reviewed, 44 met the inclusion criteria. The parameters that measured the preoperative position of LIV and ratio of MT: TL/L curve showed high correlation with the 2-year thoracic AV-CSVL distance. With regard to the parameters that measured the amount of correction obtained by surgery, only the correction of the thoracic AV-T1 distance showed low correlation. Among the 18 parameters, preoperative lowest instrumented vertebra-lower end vertebra (LIV-LEV) difference and ratio of MT: TL/L Cobb angle were selected to form a formula to help predict postoperative trunk shift. The formula was as follows: 2-year thoracic AV-CSVL distance = -26.6 + 22.7 (ratio of MT: TL/L Cobb angle) - 3.9 (preoperative LIV-LEV difference). The model R = 0.55. CONCLUSION.: Both LIV selection and ratio of MT: TL/L curve were found to be highly correlated with the onset of postoperative trunk shift in Lenke 1C scoliosis. Amount of correction obtained by surgery, however, did not seem to be an independent causative factor. Postoperative trunk shift is less likely to occur when selecting LEV as LIV and the ratio of MT: TL/L Cobb angle of 1.2° or more.

Objective: To examine the effect of an alternative wound closure method after tumor arthroplasty of the hip compared to routine wound closure with skin staples. Method: Single center, frequency matched cohort study. We reviewed all patients who underwent tumor resection and endoprosthetic reconstruction of the proximal femur for pathologic fracture due to metastatic bone disease or malignant hematologic bone disease at our center between 2010 and 2014. All patients treated with occlusive wound closure (OWC), a combination of intradermal suture, Steri-Strips™, and an occlusive skin adhesive, during this period ( n = 35), were compared to an equally sized frequency matched group of patients having undergone routine wound closure with conventional skin staples. Results: Patients with OWC were significantly faster to achieve dry wound status and consequently had significantly shorter administration of antibiotics and hospital stay. Compared to the patients with conventional wound closure with staples, their wounds were already dry after a mean 3.4 days (vs. 6.7 days [95%CI: 3–3.8 vs. 5.5–7.9], p < 0.0001), they received antibiotics for a mean 4.2 days (vs. 6.8 days [95%CI: 3.7–4.8 vs. 5.5–8.0], p < 0.0003) and their mean hospital stay was 6.3 days (vs. 8.0 days [95%CI: 5.5–7 vs. 6.8–9.3], p < 0.015). Prolonged wound discharge (PWD) for 7 days or more was observed in 34% of patients ( n = 12) in the conventional group, whereas this complication was completely absent ( n = 0) in the investigational group. For every three patients treated with OWC, one complication of PWD over 7 days is avoided (number needed to treat = 3). Conclusion: Compared to conventional staples, OWC appears to significantly reduce wound complications, use of antibiotics, and hospital stay in patients undergoing tumor arthroplasty procedures of the hip. As such, it may also contribute to a reduction of the substantially increased risk for prosthetic joint infection in this patient population.

Objective Maternal rheumatoid arthritis (RA) has been associated with an increased risk of autism spectrum disorder (ASD) in the offspring. We assessed the potential influence of both maternal and paternal RA on the risk of ASD in offspring to disentangle the influence of genetic inheritance from other conditions potentially leading to fetal programming. Method The nationwide cohort study included all children born alive from 1977 to 2008 in Denmark (N = 1,917,723). Cox regression models were used to calculate hazard rate ratios (HR) of ASD in offspring exposed to maternal or paternal RA, compared to unexposed children. Results Maternal RA was associated with an approximately 30% increased risk of ASD in the offspring (HR = 1.31 and 95% CI = 1.06−1.63). Also, paternal RA seemed to increase the risk of ASD by approximately 30% (HR = 1.33, 95% CI = 0.97−1.82). Conclusion Our findings suggest maternal as well as paternal RA to be associated with an increased risk of ASD in the offspring, indicating that genetic factors associated with RA may also play a role in the etiology of ASD in children of parents with RA.

OBJECTIVE: To estimate the influence of parental rheumatoid arthritis (RA) on child morbidity.DESIGN: Nationwide cohort study.SETTING: Individual linkage to nationwide Danish registries.PARTICIPANTS: All singletons born in Denmark during 1977-2008 (n=1 917 723) were followed for an average of 16 years.MAIN OUTCOME MEASURES: Adjusted HRs for child morbidity; that is, 11 main diagnostic groups and specific autoimmune diseases within the International Classification of Diseases 8th and 10th versions.RESULTS: Compared with unexposed children, children exposed to maternal RA ('clinical' and 'preclinical') (n=13 566) had up to 26% higher morbidity in 8 of 11 main diagnostic groups. Similar tendencies were found in children exposed to paternal RA ('clinical' and 'preclinical') (n=6330), with statistically significantly higher morbidity in 6 of 11 diagnostic groups. HRs were highest for autoimmune diseases with up to three times increased risk of juvenile idiopathic arthritis (HR, 95% CI 3.30, 2.71 to 4.03 and 2.97, 2.20 to 4.01) and increased risk of up to 40% of diabetes mellitus type 1 (HR, 95% CI 1.37, 1.12 to 1.66 and 1.44, 1.09 to 1.90) and up to 30% increased HR of asthma (HR, 95% CI 1.28, 1.20 to 1.36 and 1.15, 1.04 to 1.26). Conclusions were roughly similar for children exposed to maternal clinical RA and for children only followed up to 16 years of age.CONCLUSION: Children of parents with RA had consistent excess morbidity. If the associations reflect biological mechanisms, genetic factors seem to play an important role. These findings call for attention given to children of parents with RA.

BACKGROUND AND OBJECTIVE: Oxytocin for labor augmentation is widely used in obstetric care in Western countries. Two recent, smaller studies found opposing results regarding the association between prenatal exposure to oxytocin for labor augmentation and attention-deficit/hyperactivity disorder (ADHD). In Denmark, oxytocin is the medication used for nearly all medical augmentations of labor, and we examined the association between medical augmentation of labor and ADHD in a large cohort study based on national register data. METHODS: All singletons born after spontaneous onset of labor in Denmark between 2000 and 2008 (N = 546 146) were included in the study. Data from the Danish Medical Birth Registry on medical augmentation of labor (yes/no) were used to identify exposed children. ADHD was defined based on the diagnostic codes of International Classification of Diseases, 10th Revision, for hyperkinetic disorder and information on dispensed ADHD medication. A multivariate proportional hazards regression model was used to test the association. RESULTS: Among 546 146 deliveries, 26% included medical augmentation of labor, and 0.9% of the children were identified as having ADHD (n = 4617). We found no association between augmentation of labor and ADHD in the offspring (hazard ratio: 1.05 [95% confidence interval: 0.98–1.13]). CONCLUSIONS: Our study does not support an association between medical augmentation of labor and ADHD in the child.

Background Preeclampsia is a possible risk factor for childhood asthma in the offspring. Our aim was to find whether preeclampsia is associated with childhood asthma. We also aimed to study whether a possible association can be explained by factors shared by siblings. Methods All eligible live singletons born in Denmark during 1993–2007 were identified (N = 923,533), and the occurrence of preeclampsia during the index pregnancy was determined. The children were followed from their 3rd birthday to the first hospitalization, outpatient contact or prescription for asthma, emigration, death, their 18th birthday, or the end of 2010, whichever came first. We carried out a nested case-control and a case-sibling study with density sampling to estimate incidence rate ratio (IRR) of asthma as a function of maternal preeclampsia, using conditional logistic regression. Results A total of 115,522 asthma cases were identified during 1996–2010. In the case-control analysis, the overall IRR of asthma for those exposed to maternal preeclampsia was 1.19 (95% confidence interval (CI): 1.15, 1.24). The IRRs for asthma according to early and late onset preeclampsia were 1.88 (95% CI: 1.67, 2.11) and 1.14 (95% CI: 1.10, 1.19). In the case-sibling analysis, the corresponding IRRs were 1.06 (95% CI: 0.98, 1.14), 1.15 (95% CI: 1.02, 1.29), and 1.02 (95% CI: 0.93, 1.11), respectively. Conclusions Early onset preeclampsia was associated with an increased risk of asthma in the offspring, but part of this association may be due to confounding by factors shared by siblings.

BACKGROUND: Cryptorchidism (undescended testis) is a common anomaly with largely unexplained etiology. Animal studies have suggested maternal emotional stress as a potential risk factor, but this has not been studied in humans. We aimed to investigate whether maternal bereavement due to the death of a close relative in the antenatal period increases the occurrence of cryptorchidism in the offspring.METHODS: In a population-based cohort, we studied death of a close relative as the exposure and cryptorchidism entries in nationwide medical registries as the outcome. Danish national registries included 898,961 (23,609 exposed) boys born from 1978 to 2008 with a maximum of 30 years of follow-up.RESULTS: A total of 20,947 boys had cryptorchidism, of whom 13,524 also underwent corrective surgery. We found no increased occurrence of cryptorchidism in the offspring (hazard ratio = 1.02 [95% confidence interval = 0.92-1.14]). Results were similar when the diagnosis was verified with surgery. We adjusted for maternal and paternal age, birth year, and family history of cryptorchidism.CONCLUSION: We observed no association between maternal bereavement before and during pregnancy and the occurrence of cryptorchidism in the offspring.

Depression forekommer ofte efter en kræftdiagnose og forbindes med øget mortalitet. Det er dog uvist, om depression i perioden før en kræftdiagnose også påvirker mortaliteten. Dette studie undersøger mortaliteten hos patienter, som blev behandlet med antidepressiv medicin før en kræftdiagnose. Resultaterne viser, at over 33.000 patienter (16,4 %) indløste mindst en recept med antidepressiv medicin i løbet af de seneste tre år før en kræftdiagnose. Heraf fik knap 22.000 (10.8 %) af disse patienter stadig medicinen på tidspunktet for kræftdiagnosen. For aktuelle brugere sås en 32 % højere 1-årsmortalitet end for ikke-brugere. Denne stigning gjaldt særlig patienter, som påbegyndte behandling med antidepressiv medicin inden for de seneste fire måneder før kræftdiagnosen, mens der ikke sås en øget risiko for tidligere brugere. Ligeledes sås en 22 % højere 5-årsmortalitet for de patienter, der overlevede det første år efter kræftdiagnosen. Konklusionen er, at påbegyndelse af behandling med antidepressiv medicin før en kræftdiagnose er forholdsvis hyppig, og at denne behandling forbindes med øget mortalitet. Studiet er gennemført som et populationsbaseret kohortestudie og omfatter data fra over 200.000 danskere, som blev diagnosticeret med kræft i perioden 2003-2010. BACKGROUND: Depression is common after a cancer diagnosis and is associated with an increased mortality, but it is unclear whether depression occurring before the cancer diagnosis affects cancer mortality. We aimed to study cancer mortality of people treated with antidepressants before cancer diagnosis.METHODS AND FINDINGS: We conducted a population based cohort study of all adults diagnosed with cancer between January 2003 and December 2010 in Denmark (N = 201,662). We obtained information on cancer from the Danish Cancer Registry, on the day of death from the Danish Civil Registry, and on redeemed antidepressants from the Danish National Prescription Registry. Current users of antidepressants were defined as those who redeemed the latest prescription of antidepressant 0-4 months before cancer diagnosis (irrespective of earlier prescriptions), and former users as those who redeemed the latest prescription five or more months before cancer diagnosis. We estimated an all-cause one-year mortality rate ratio (MRR) and a conditional five-year MRR for patients who survived the first year after cancer diagnosis and confidence interval (CI) using a Cox proportional hazards regression model. Overall, 33,111 (16.4%) patients redeemed at least one antidepressant prescription in the three years before cancer diagnosis of whom 21,851 (10.8%) were current users at the time of cancer diagnosis. Current antidepressant users had a 32% higher one-year mortality (MRR = 1.32, 95% CI: 1.29-1.35) and a 22% higher conditional five-year mortality (MRR = 1.22, 95% CI: 1.17-1.26) if patients survived the first year after the cancer diagnosis than patients not redeeming antidepressants. The one-year mortality was particularly high for patients who initiated antidepressant treatment within four months before cancer diagnosis (MRR = 1.54, 95% CI: 1.47-1.61). Former users had no increased cancer mortality.CONCLUSIONS: Initiation of antidepressive treatment prior to cancer diagnosis is common and is associated with an increased mortality.

Author(s): Streja, Elani; Miller, Jessica E; Wu, Chunsen; Bech, Bodil H; Pedersen, Lars Henning; Schendel, Diana E; Uldall, Peter; Olsen, Jorn | Abstract: ObjectiveTo investigate the association between proportionality of fetal and placental growth measured at birth and the risk for congenital cerebral palsy (CP).Study designWe identified all live-born singletons born in Denmark between 1995 and 2003 and followed them from 1 year of age until December 31st, 2008. Information on four indices of fetal growth: ponderal index, head circumference/ abdominal circumference ratio, cephalization index and birth weight/ placenta weight ratio was collected. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). All measurements were evaluated as gestational age and sex specific z-scores and in z-score percentile groups, adjusted for potential confounders, and stratified on gestational age groups (l32, 32-36, 37-38, 39, 40, ≥ 41 weeks).ResultsWe identified 503,784 singleton births, of which 983 were confirmed cases of CP. Head/ abdominal circumference ratio (aHR:1.12; 95%CI:1.07-1.16) and cephalization index (aHR:1.14; 95%CI:1.11-1.16) were associated with the risk of CP irrespective of gestational age. Birth weight-placental weight ratio was also associated with CP in the entire cohort (aHR:0.90; 95%CI:0.83-0.97). Ponderal index had a u-shaped association with CP, where both children with low and high ponderal index were at higher risk of CP.ConclusionsCP is associated with disproportions between birth weight, birth length, placental weight and head circumference suggesting pre and perinatal conditions contribute to fetal growth restriction in children with CP.

STUDY DESIGN:: A correlation study.OBJECTIVE:: The primary objective was to determine the correlation between radiologic and cosmetic indices of trunk and shoulder balance before and after scoliosis surgery in Lenke 1C adolescent idiopathic scoliosis (AIS) and to determine whether postoperative trunk shift is affiliated with worsening of the patients' cosmesis.SUMMARY OF BACKGROUND DATA:: Achieving a symmetrical appearance with truncal and shoulder balance is of prime importance to AIS patients and their surgeons. However, surgeons prefer radiographic indices rather than measures of patients' clinical appearance. If radiographic indices are to be considered accurate depictions of the patient's cosmesis, radiologic- and cosmetic indices must necessarily exhibit high association.METHODS:: Radiographic and cosmetic indices of trunk and shoulder balance, along with posterior trunk symmetry index (POTSI), were measured preoperatively and three months postoperatively in 33 Lenke 1C scoliosis patients. Pearson's correlation analysis was performed. Paired t-test was used to determine significant changes in radiographic and cosmetic indices after surgery. Independent sample t-test was used for all inter-group analyses in trunk shift and no-trunk-shift groups.RESULTS:: Correlation coefficients between radiologic and cosmetic indices ranged between -0.63-0.70 with thoracic apical vertebra-central sacral vertical line (AV-CSVL) distance and first rib angle (FRA) showing consistent correlations with cosmetic trunk and cosmetic shoulder balance indices. Trunk shift, a postoperative iatrogenic phenomenon, was seen in 19 (58%) patients. These patients had higher preoperative thoracic apical vertebra-central sacral vertical line (AV-CSVL) translation, thoracic apical vertebra-first thoracic vertebra (AV-T1) translation, thoracic deformity correction rate, AV-T1 correction rates and shorter fusions compared to the no-trunk-shift group. POTSI index worsened in trunk shift group and improved significantly (-7.94 vs. 16.53) in no-trunk shift group. Significant association (P=0.004) was seen between radiographic and cosmetic trunk shift.CONCLUSION:: Radiographic indices can only minisculely (r≤0.7) reflect cosmetic deformity in Lenke 1C scoliosis, which emphasizes not only the vulnerability of over-reliance on radiographic indices but also the vital importance of clinical cosmetic evaluations. In particular, cosmetic shoulder height and angle are not represented by radiographic indices. However, radiograph trunk shift was significantly associated with cosmetic trunk shift in cosmetic pictures.

OBJECTIVE: Lack of maternal thyroid hormones during foetal brain development may lead to structural abnormalities in the brain. We hypothesized that maternal hypothyroidism during the pregnancy could programme the foetus to development of psychiatric disease later in life.DESIGN: Danish nationwide register study.PARTICIPANTS: Singletons live-born 1980-1990.MEASUREMENTS: Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) with 95% confidence interval for offspring redemption of ≥2 prescriptions of a psychiatric drug from age 15 to 31 years.RESULTS: Among 542 100 adolescents and young adults included, altogether 3979 (0·7%) were born to mothers with hypothyroidism registered before 1996. In crude analyses, the use of a psychiatric drug was more frequent in late adolescence and young adulthood when the mother had hypothyroidism (P < 0·001); however, several possible confounders had to be taken into account. For example, mothers with hypothyroidism often also had a psychiatric registration (38·5% vs 27·7%, P < 0·001) and the use of psychiatric drugs changed over time. After adjustment for confounders including birth year, maternal age and maternal psychiatric history, maternal hypothyroidism was associated with an increased risk of having redeemed prescriptions of anxiolytics [aHR 1·23 (1·03-1·48)] and antipsychotics [aHR 1·22 (1·03-1·44)] in late adolescence and young adulthood. For antidepressants, aHR was 1·07 (0·98-1·17).CONCLUSIONS: The association between maternal hypothyroidism and the use of a psychiatric drug in late adolescence and young adulthood was partly confounded by maternal psychiatric history, but foetal programming by maternal hypothyroidism may be part of the mechanisms leading to the use of anxiolytics and antipsychotics.

OBJECTIVE Smoking may influence on the occurrence of thyroid disease, but studies have led to inconsistent results. In Denmark, information on maternal smoking during pregnancy is registered by midwives, and we investigated the association between maternal smoking as reported during pregnancy and the subsequent maternal risk of having hyper- or hypothyroidism diagnosed. DESIGN Population-based cohort study. PARTICIPANTS Using Danish nationwide registers, we identified mothers giving birth in Denmark, 1996-2008, and studied their first pregnancy in the study period. MEASUREMENTS Information on maternal smoking during the pregnancy and maternal diagnosis of hyper- or hypothyroidism was obtained from the Danish National Hospital Register (DNHR) and prescription of thyroid medication from the Danish National Prescription Register (DNPR). Cox proportional hazards model was used to estimate hazard ratio (HR) with 95% confidence interval (95% CI) for onset of maternal hyper- or hypothyroidism after birth of the child in multivariate analyses adjusting for potential confounders. RESULTS Among mothers included (n = 450 842), altogether 89,022 (19·7%) reported that they were smokers during the first pregnancy in the study period, and 8905 (2·0%) developed hyper (n = 3389)- or hypothyroidism (n = 5516) after birth of the child. Maternal smoking was associated with a subsequent decreased risk of developing hypothyroidism (adjusted HR 0·75 (95% CI 0·70-0·81)) and an increased risk of hyperthyroidism (1·38 (1·27-1·49)). CONCLUSIONS Danish nationwide registration of maternal smoking during pregnancy adds further evidence to an association between smoking and thyroid dysfunction; smoking reduced the risk of hypothyroidism and increased the risk of hyperthyroidism.

Background Childbirth is a demanding event in a woman's life. The aim of this study was to explore whether a brief intervention in the form of an antenatal course in self-hypnosis to ease childbirth could improve the childbirth experience. Method In a randomized, controlled, single-blinded trial, 1,222 healthy nulliparous women were allocated to one of three groups during pregnancy: A hypnosis group participating in three 1-hour sessions teaching self-hypnosis to ease childbirth, a relaxation group receiving three 1-hour lessons in various relaxation methods and Mindfulness, and a usual care group receiving ordinary antenatal care only. Wijmas Delivery Expectancy/Experience Questionnaire (W-DEQ) was used to measure the childbirth experience 6 weeks postpartum. Results The intention-to-treat analysis indicated that women in the hypnosis group experienced their childbirth as better compared with the other two groups (mean W-DEQ score of 42.9 in the Hypnosis group, 47.2 in the Relaxation group, and 47.5 in the Care as usual group (p = 0.01)). The tendency toward a better childbirth experience in the hypnosis group was also seen in subgroup analyses for mode of delivery and for levels of fear. Conclusion In this large randomized controlled trial, a brief course in self-hypnosis improved the women's childbirth experience.

Hyperthyroidism in pregnant women should be adequately treated to prevent maternal and fetal complications, but teratogenic effects of antithyroid drug (ATD) treatment have been described. Evidence is still lacking in regard to the safety and choice of ATD in early pregnancy.Our objective was to determine to which degree the use of methimazole (MMI)/carbimazole (CMZ) and propylthiouracil (PTU) in early pregnancy is associated with an increased prevalence of birth defects.This Danish nationwide register-based cohort study included 817 093 children live-born from 1996 to 2008. Exposure groups were assigned according to maternal ATD use in early pregnancy: PTU (n = 564); MMI/CMZ (n = 1097); MMI/CMZ and PTU (shifted in early pregnancy [n = 159]); no ATD (ATD use, but not in pregnancy [n = 3543]); and nonexposed (never ATD use [n = 811 730]). Multivariate logistic regression was used to estimate adjusted odds ratio (OR) with 95% confidence interval (95% CI) for diagnosis of a birth defect before 2 years of age in exposed versus nonexposed children.The prevalence of birth defects was high in children exposed to ATD in early pregnancy (PTU, 8.0%; MMI/CMZ, 9.1%; MMI/CMZ and PTU, 10.1%; no ATD, 5.4%; nonexposed, 5.7%; P.001). Both maternal use of MMI/CMZ (adjusted OR = 1.66 [95% CI 1.35-2.04]) and PTU (1.41 [1.03-1.92]) and maternal shift between MMI/CMZ and PTU in early pregnancy (1.82 [1.08-3.07]) were associated with an increased OR of birth defects. MMI/CMZ and PTU were associated with urinary system malformation, and PTU with malformations in the face and neck region. Choanal atresia, esophageal atresia, omphalocele, omphalomesenteric duct anomalies, and aplasia cutis were common in MMI/CMZ-exposed children (combined, adjusted OR = 21.8 [13.4-35.4]).Both MMI/CMZ and PTU were associated with birth defects, but the spectrum of malformations differed. More studies are needed to corroborate results in regard to early pregnancy shift from MMI/CMZ to PTU. New ATD with fewer side effects should be developed.

PURPOSE: To examine correlation between postoperative radiographic and cosmetic improvements in Lenke 1C adolescent idiopathic scoliosis (AIS) with patients' self-rated outcomes of health and disability at follow-up as determined by the Scoliosis Research Society questionnaire (SRS-30), Oswestry Disability Index score (ODI) and measure of overall health quality Euroqol-5d (EQ-5D).METHODS: 24 Lenke 1C scoliosis patients, mean age 16.5 (12.8-38.1) years, treated with posterior pedicle screw-only construct, were included. The coronal profile indices (radiographic and cosmetic) regarding magnitude of spinal deformity and truncal balance were measured preoperatively, postoperatively and at final follow-up. A comprehensive index of overall back symmetry was also measured by means of the Posterior Trunk Symmetry Index (POTSI). Pearson's correlation analysis determined the association between the radiographic-cosmetic indices and patient-rated outcomes.RESULTS: Mean follow-up for the cohort was 4.4 (±1.86) years. The thoracic apical vertebra-first thoracic vertebra horizontal distance (AV-TI) correction had significant correlation with function, self-image, and mental health SRS-30 scores (0.55, 0.54, 0.66). Similarly, thoracic apical vertebra horizontal translation from central sacral vertical line (AV-CSVL) correction at follow-up had significant correlation with self-image and management domains (0.57, 0.50). Follow-up POTSI correlated well with SRS-30 and EQ-5D scores (r = -0.64, -0.54). Postoperative leftward trunk shift/spinal imbalance did not influence overall cosmesis and outcomes; significant spinal realignment was evident in follow-up resulting in physiological balance and acceptable cosmesis and outcomes.CONCLUSION: Significant, but less than "perfect" correlations were observed between the radiographic, cosmetic measures and patient-rated outcomes. Thoracic AV-CSVL, AV-T1 correction and POTSI associated significantly with SRS-30 scores. Whereas, thoracic Cobb angle, Cobb correction, and coronal balance did not correlate with any patient-rated outcome measure. It is, therefore, inferred that the patients-rated subjective outcomes are only poorly reflected by the objectively measured radiographic and cosmetic measures of deformity correction.

STUDY QUESTION: Is maternal bereavement (emotional stress) due to loss of a close relative in the antenatal period associated with the risk of oral cleft in the offspring?SUMMARY ANSWER: Our study suggests prenatal maternal bereavement is associated with an increased risk of oral cleft in the offspring, especially when the bereavement was due to a sudden death or death of a child.WHAT IS KNOWN ALREADY: The aetiology of oral cleft is unknown but includes both genetic and environmental causes.STUDY DESIGN, SIZE AND DURATION: We performed a population-based cohort study based on several national registers in Denmark from 1978 to 2008.PARTICIPANTS/MATERIALS, SETTING, METHODS: Our final study population consisted of 1 771 663 children. Of these 35 118 (2%) were born to mothers who experienced bereavement in the exposure window from 1 year before pregnancy to the end of the first trimester.MAIN RESULTS AND THE ROLE OF CHANCE: In total, 3043 children were diagnosed with a cleft; 968 with cleft lip, 1206 with cleft lip and palate and 869 with a cleft palate. For overall bereavement the prevalence was 1.7 per 1 000 live born in the unexposed children and 2.2 per 1 000 live born in the exposed children. Overall, maternal bereavement due to the death of a close relative from 1 year before conception to the end of the first trimester was associated with a significantly increased risk of oral cleft [odds ratio (OR): 1.28, 95% confidence interval (CI): 1.01; 1.61). When mothers lost a relative due to a sudden death, the risk of oral cleft in the offspring was higher (OR: 1.76, 95% CI: 1.06; 2.94). Losing a relative in the time period before pregnancy and during the first trimester showed a tendency to an increased risk. The risk increase was 77% when the mother was bereaved due to sudden death and the estimation was robust in different analytical strategies.LIMITATIONS, REASONS FOR CAUTION: It is a limitation that we only studied live born children, but most children with isolated oral cleft would survive their pregnancy and birth. Since oral cleft are rare and despite the large study population, we still had a relatively small number of cases, which results in limited power to detect small differences. We did not have actual measurements of the maternal cortisol concentration, but we believe that bereavement due to death of a close relative produces a strong stress reaction in most people. Also we did not have the opportunity to adjust for intake of folic acid and use of anti-depressant; however, analysis in a subset of the data showed no difference in these intakes between exposed and unexposed mothers.WIDER IMPLICATIONS OF THE FINDINGS: With this study we add a large-scale human cohort study to the body of literature on stress and birth defects. Our study is in agreement with previously published results and can be generalized to similar populations like the native Danish population. Severe stress may be added to the list of potential causes for oral cleft.

Author(s): Wu, Chun S; Pedersen, Lars H; Miller, Jessica E; Sun, Yuelian; Streja, Elani; Uldall, Peter; Olsen, Jorn | Abstract: Background and aimMaternal infections during pregnancy have been associated with several neurological disorders in the offspring. However, given the lack of specificity for both the exposures and the outcomes, other factors related to infection such as impaired maternal immune function may be involved in the causal pathway. If impaired maternal immune function plays a role, we would expect infection before pregnancy to be associated with these neurological outcomes.Methods/principal findingsThe study population included all first-born singletons in Denmark between January 1 1982 and December 31 2004. We identified women who had hospital-recorded infections within the 5 year period before pregnancy, and women who had hospital-recorded infections during pregnancy. We grouped infections into either infections of the genitourinary system, or any other infections. Cox models were used to estimate adjusted hazard ratios (aHRs) with 95% confidence interval (CI). Maternal infection of the genitourinary system during pregnancy was associated with an increased risk of cerebral palsy (aHR = 1.63, 95% CI: 1.34-1.98) and epilepsy (aHR = 1.27, 95% CI: 1.13-1.42) in the children, compared to children of women without infections during pregnancy. Among women without hospital-recorded infections during pregnancy, maternal infection before pregnancy was associated with an increased risk of epilepsy (aHR = 1.35, 95% CI: 1.21-1.50 for infections of the genitourinary system, and HR = 1.12, 95% CI: 1.03-1.22 for any other infections) and a slightly higher risk of cerebral palsy (aHR = 1.20, 95% CI: 0.96-1.49 for infections of the genitourinary system, and HR = 1.23, 95% CI: 1.06-1.43 for any other infections) in the children, compared to children of women without infections before (and during) pregnancy.ConclusionsThese findings indicate that the maternal immune system, maternal infections, or factors related to maternal immune function play a role in the observed associations between maternal infections before pregnancy and cerebral diseases in the offspring.

BackgroundPlacental transport of iodide is required for fetal thyroid hormone production. The sodium iodide symporter (NIS) mediates active iodide transport into the thyroid and the lactating mammary gland and is also present in placenta. NIS is competitively inhibited by thiocyanate from maternal smoking, but compensatory autoregulation of iodide transport differs between organs. The extent of autoregulation of placental iodide transport remains to be clarified.ObjectiveTo compare the impact of maternal smoking on thyroglobulin (Tg) levels in maternal serum at delivery and in cord serum as markers of maternal and fetal iodine deficiency.MethodsOne hundred and forty healthy, pregnant women admitted for delivery and their newborns were studied before the iodine fortification of salt in Denmark. Cotinine in urine and serum classified mothers as smokers (n=50) or nonsmokers (n=90). The pregnant women reported on intake of iodine-containing supplements during pregnancy and Tg in maternal serum at delivery and in cord serum were analyzed.ResultsIn a context of mild-to-moderate iodine deficiency, smoking mothers had significantly higher serum Tg than nonsmoking mothers (mean Tg smokers 40.2 vs nonsmokers 24.4 μg/l, P=0.004) and so had their respective newborns (cord Tg 80.2 vs 52.4 μg/l, P=0.006), but the ratio between Tg in cord serum and maternal serum was not significantly different in smokers compared with nonsmokers (smoking 2.06 vs nonsmoking 2.22, P=0.69).ConclusionMaternal smoking increased the degree of iodine deficiency in parallel in the mother and the fetus, as reflected by increased Tg levels. However, placental iodide transport seemed unaffected despite high thiocyanate levels, suggesting that thiocyanate-insensitive iodide transporters alternative to NIS are active or that NIS in the placenta is autoregulated to keep iodide transport unaltered.