Prenatal stress, anxiety and depression alter transcripts, proteins and pathways associated with immune responses at the maternal-fetal interface†.

During pregnancy, the immune system is modified to allow developmental tolerance of the semi-allogeneic fetus and placenta to term. Pregnant women suffering from stress, anxiety, and depression show dysfunctions of their immune system that may be responsible for fetal and/or newborn disorders, provided that placental gene regulation is compromised. The present study explored the effects of maternal chronic self-perceived stress, anxiety, and depression during pregnancy on the expression of immune-related genes and pathways in term placenta. Pregnancies were clinically monitored with the Beck Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 divided patients into two groups: Index group (>10, n = 11) and a Control group (<10, n = 11), whose placentae were sampled at delivery. The placental samples were subjected to RNA-Sequencing, demonstrating that stress, anxiety, and depression during pregnancy induced a major downregulation of placental transcripts related to immune processes such as T-cell regulation, interleukin and cytokine signaling, or innate immune responses. Expression differences of main immune-related genes, such as CD46, CD15, CD8α & ß ILR7α, and CCR4 among others, were found in the Index group (P < 0.05). Moreover, the key immune-like pathway involved in humoral and cellular immunity named "Primary immunodeficiency" was significantly downregulated in the Index group compared with Controls. Our results show that mechanisms ruling immune system functions are compromised at the maternal-fetal interface following self-perceived depressive symptoms and anxiety during pregnancy. These findings may help unveil mechanisms ruling the impact of maternal psychiatric symptoms and lead to new prevention/intervention strategies in complicated pregnancies.

Study protocol for a modified antenatal care program for pregnant women with a low risk for adverse outcomes-a stepped wedge cluster non-inferiority randomized trial.

BACKGROUND: It is crucial to provide care based on individual needs. Swedish health care is obliged to give care on equal conditions for the entire population. The person with the greatest need should be given the most care, and the health care system should strive to be cost-efficient. Medical and technical advances have been significant during the last decades and the recent Covid-19 pandemic has caused a shift in health care, from in-person visits to virtual visits. The majority of pregnant women with a low risk assessment have an uncomplicated antenatal course without adverse events. These women probably receive excessive and unnecessary antenatal care. This study will investigate if an antenatal care program for healthy pregnant women with a low risk for adverse outcomes could be safely monitored with fewer in-person visits to a midwife, and with some of them replaced by virtual visits. METHODS: This is a non-inferiority trial where a stepped wedge cluster randomized controlled design will be used. Data collection includes register data and questionnaires that concern antenatal, obstetric and neonatal outcomes, patient- and caregiver-reported experiences, healthcare-economy, and implementation aspects. The modified antenatal care (MAC) study is performed in parts of the southeast of Sweden, which has approximately 8200 childbirths annually. At the start of the study, all antenatal care centers included in the study will use the same standard antenatal care (SAC) program. In the MAC program the in-person visits to a midwife will be reduced to four instead of eight, with two additional virtual meetings compared with the SAC program. DISCUSSION: This presented study protocol is informed by research knowledge. The protocol is expected to provide a good structure for future studies on changed antenatal care programs that introduce virtual visits for healthy pregnant women with a low risk for adverse outcomes, without risking quality, safety, and increased costs. TRIAL REGISTRATION: The study is registered the 21th of April 2021 in the ISRCTN registry with trial ID: ISRCTN14422582 , retrospectively registered.

Size for gestational age affects the risk for type 1 diabetes in children and adolescents: a Swedish national case-control study.

AIM/HYPOTHESIS: Environmental factors are believed to contribute to the risk of developing type 1 diabetes. The aim of this study was to investigate how size for gestational age affects the risk of developing childhood type 1 diabetes. METHODS: Using the Swedish paediatric diabetes quality register and the Swedish medical birth register, children with type 1 diabetes diagnosed between 2000 and 2012 (n = 9376) were matched with four control children (n = 37,504). Small for gestational age (SGA) and large for gestational age (LGA) were defined according to Swedish national standards. Data were initially analysed using Pearson's χ2 and thereafter by single and multiple logistic regression models. RESULTS: An equal proportion of children were born appropriate for gestational age, but children with type 1 diabetes were more often born LGA and less often born SGA than control children (4.7% vs 3.5% and 2.0% vs 2.6%, respectively, p < 0.001). In the multiple logistic regression analysis, being born LGA increased (adjusted OR 1.16 [95% CI 1.02, 1.32]) and SGA decreased (adjusted OR 0.76 [95% CI 0.63, 0.92]) the risk for type 1 diabetes, regardless of maternal BMI and diabetes. CONCLUSIONS/INTERPRETATION: Size for gestational age of Swedish children affects the risk of type 1 diabetes, with increased risk if the child is born LGA and decreased risk if the child is born SGA. Being born LGA is an independent risk factor for type 1 diabetes irrespective of maternal BMI and diabetes. Thus, reducing the risk for a child being born LGA might to some extent reduce the risk for type 1 diabetes.

Mental disorders and risk factors among pregnant women with depressive symptoms in Sweden-A case-control study.

INTRODUCTION: Identification of pregnant women suffering from depression or other mental disorders is a challenge for antenatal caregivers. The purpose of this case-control study was to describe mental disorders and the risk factors for mental disorders in women with depressive symptoms assessed with the Edinburgh Postnatal Depression Scale during the first trimester and to compare them with pregnant women without depressive symptoms. MATERIAL AND METHODS: In total, 2271 women answered the Edinburgh Postnatal Depression Scale at the first antenatal visit with a midwife. An Edinburgh Postnatal Depression Scale score of 13 or higher was considered to be screen-positive and these women were further assessed. Screen-negative pregnant women, matched for age and parity, were chosen as controls. RESULTS: In total, 149 (6.6%) women were found to be screen-positive. The majority (126, 85%) had at least one mental disorder or risk factor for mental disorder, such as depression (36.0%), anxiety (14.8%), or severe fear of childbirth (20.8%). The screen-positive women were more often smokers (16.1% vs 1.3%), unemployed (19.9% vs 1.3%), or on sick leave (25.3% vs 14.1%) during pregnancy and more often used selective serotonin reuptake inhibitor during pregnancy (14.2% vs 2.7%) compared with the screen-negative women (P<.001). Among the screen-negative women (n = 150) only three (2%) presented with symptoms of depression during pregnancy. CONCLUSIONS: The Edinburgh Postnatal Depression Scale seems to be a valuable screening tool to detect depressive symptoms as well as other mental disorders during early pregnancy.

Risk factors during pregnancy and delivery for the development of Perthes' disease, a nationwide Swedish study of 2.1 million individuals.

BACKGROUND: To ascertain or disprove a correlation between suboptimal birth characteristics, breech position at delivery and development of Perthes' disease. METHODS: Study material was collected from nationwide registers regarding diagnoses, birth statistics and delivery data. As study population were included children with a diagnosis code for Perthes' disease who were alive and living in Sweden at age 13. Children with missing birth statistics were excluded. All children with no Perthes' disease diagnosis were used as control group. Both single and multiple logistical regression analyses were used to calculate OR for the included characteristics. RESULTS: Children in breech position had a higher risk for developing Perthes' disease. Children with Perthes' disease had also a higher probability of having been born pre-term, very pre-term or post-term. Lower than normal birth weight and a lower Apgar-score were also associated with Perthes' disease. CONCLUSIONS: There is a correlation between breech birth and development of Perthes' disease. There is also correlation to suboptimal birth characteristics. Despite our findings this should not be used for screening of Perthes' disease as the percentage of children who actually develop it is very low. Also, as of yet there is no possibility to diagnose Perthes' disease before the presence of skeletal changes. Our findings could be important in finding the cause of Perthes' disease and therefore developing better diagnostics, treatment and prevention.

Reproduction, fear of childbirth and obstetric outcomes in women treated for fear of childbirth in their first pregnancy: A historical cohort.

INTRODUCTION: About 8% of the pregnant women in Sweden receive counseling for fear of childbirth (FOC) during pregnancy. Little is known about the long-term reproductive and obstetric outcomes after counseling for FOC: Therefore, the objective of this historical cohort study was to compare the long-term reproductive and obstetric outcomes in women treated for FOC in their first pregnancy to women without FOC. MATERIAL AND METHODS: All nulliparas consecutively referred for treatment of severe FOC between 2001 and 2007 (n = 608) were compared with all other nulliparas giving birth on the same day (n = 431). Women who were not fluent in Swedish, missing a postal address, had moved out of the area, given birth at another hospital or had a late spontaneous abortion were excluded (n = 555). A total of 235 women agreed to participate in the study, 63 (39%) women in the index group and 172 (53%) in the reference group. The women were contacted by letter in 2015, ie 7-14 years after first childbirth, and asked to permit access to their medical charts from pregnancies and childbirths and to fill out a study specific questionnaire. Based on data from the medical charts and questionnaire, the mode of delivery, birth experience, obstetric complications, FOC, counseling for FOC and number of childbirths were compared in the two groups. RESULTS: Women in the index group less often gave birth more than twice compared with the reference group (8.2% vs 22.0%, P = 0.012). We found no significant differences in complications during subsequent pregnancies and deliveries. Women in the index group more often gave birth by CS in their first (P = 0.002) and second childbirth (P = 0.001), more often had a less positive birth experience (index group NRS: median 6.0, interquartile range 6 vs reference group NRS: 7.0, interquartile range 5, P = 0.004) in their first delivery and more often received counseling for FOC (58.7% vs 12.5%, P < 0.001) in subsequent pregnancies. Women in the index group more often experienced FOC (18% vs 5.3%, P = 0.001) 7-14 years after first childbirth. CONCLUSIONS: FOC is not easily treated. Despite treatment and exposure to childbirth many women received treatment in their next pregnancy and still suffered from FOC 7-14 years after the first childbirth.

Maternal obesity as a risk factor for early childhood type 1 diabetes: a nationwide, prospective, population-based case-control study.

AIMS/HYPOTHESIS: Genetic and environmental factors are believed to cause type 1 diabetes. The aim of this study was to investigate the influence of maternal BMI and gestational weight gain on the subsequent risk of childhood type 1 diabetes. METHODS: Children in the Swedish National Quality Register for Diabetes in Children were matched with control children from the Swedish Medical Birth Register. Children were included whose mothers had data available on BMI in early pregnancy and gestational weight gain, giving a total of 16,179 individuals: 3231 children with type 1 diabetes and 12,948 control children. RESULTS: Mothers of children with type 1 diabetes were more likely to be obese (9% [n = 292/3231] vs 7.7% [n = 991/12,948]; p = 0.02) and/or have diabetes themselves (2.8% [n = 90/3231] vs 0.8% [n = 108/12,948]; p < 0.001) compared with mothers of control children. Gestational weight gain did not differ significantly between the two groups of mothers. In mothers without diabetes, maternal obesity was a significant risk factor for type 1 diabetes in the offspring (p = 0.04). A child had an increased risk of developing type 1 diabetes if the mother had been obese in early pregnancy (crude OR 1.20; 95% CI 1.05, 1.38; adjusted OR 1.18; 95% CI 1.02, 1.36). Among children with type 1 diabetes (n = 3231) there was a difference (p < 0.001) in age at onset in relation to the mother's BMI. Among children in the oldest age group (15-19 years), there were more mothers who had been underweight during pregnancy, while in the youngest age group (0-4 years) the pattern was reversed. CONCLUSIONS/INTERPRETATION: Maternal obesity, in the absence of maternal diabetes, is a risk factor for type 1 diabetes in the offspring, and influences the age of onset of type 1 diabetes. This emphasises the importance of a normal maternal BMI to potentially decrease the incidence of type 1 diabetes.

Drug use in pregnant women-a pilot study of the coherence between reported use of drugs and presence of drugs in plasma.

PURPOSE: In Sweden, information on drug use during pregnancy is obtained through an interview and recorded in a standardized medical record at every visit to the antenatal care clinic throughout the pregnancy. Antenatal, delivery, and neonatal records constitute the basis for the Swedish Medical Birth Register (MBR). The purpose of this exploratory study was to investigate the reliability of reported drug use by simultaneous screening for drug substances in the blood stream of the pregnant woman and thereby validate self-reported data in the MBR. METHODS: Plasma samples from 200 women were obtained at gestational weeks 10-12 and 25 and screened for drugs by using ultra-high performance liquid chromatography with time of flight mass spectrometry (UHPLC-TOF-MS). The results from the analysis were then compared to medical records. RESULTS: At the first sampling occasion, the drugs found by screening had been reported by 86% of the women and on the second sampling, 85.5%. Missed reported information was clearly associated with drugs for occasional use. The most common drugs in plasma taken in early and mid-pregnancy were meclizine and paracetamol. Two types of continuously used drugs, selective serotonin reuptake inhibitors and propranolol, were used. All women using them reported it and the drug screening revealed a 100% coherence. CONCLUSIONS: This study shows good coherence between reported drug intake and the drugs found in plasma samples, which in turn positively validates the MBR.

Anxiety in women - a Swedish national three-generational cohort study.

BACKGROUND: Findings from animal and human studies indicate that anxiety and stress have a negative influence on the child and mother. The aim of this study was to explore the risk for having an anxiety diagnosis and the impact of the diagnosis in a three generational perspective. METHODS: The information was retrieved from Swedish population-based registries. All women who gave birth between 1973 and 1977 (n 169,782), their daughters (n 244,152), and subsequently also the offspring of the daughters (n 381,953) were followed until 2013. RESULTS: We found that 4% of the mothers and 6% of the grandmothers had been diagnosed with anxiety. Women who had mothers with an anxiety disorder were more than twice as likely to have an anxiety disorder themselves compared to all other women (OR = 2.20, 95% CI = 2.04-2.30). In the third generation, the children born to mothers with an anxiety disorder, the odds ratio of being diagnosed with anxiety was more than twice as high than for the rest of the population (OR = 2.54, 95% CI = 2.01-3.20). If both the mother and the grandmother had had an anxiety disorder the odds ratio for the child having a diagnosis of anxiety was three times higher (OR = 3.11, 95% CI = 2.04-4.75). Anxiety diagnosis in the two previous generations also increased the likelihood of the child having either more than two inpatient visits or more than 10 outpatient visits (OR = 2.64, 95% CI = 2.40-2.91 and OR = 2.21, 95% CI = 2.01-2.43, respectively). CONCLUSIONS: The intergenerational effect on anxiety is high. In order to minimize the risk for further transmission of anxiety disorders, increased awareness and generous use of effective treatment regimes might be of importance.

Risk of postpartum psychosis after IVF treatment: a nationwide case-control study.

STUDY QUESTION: Is the risk of postpartum psychosis (PPP) increased in women who give birth after IVF treatment compared to after spontaneous conception? SUMMARY ANSWER: The risk of PPP is not higher in the group of women who give birth after IVF treatment compared with women who give birth after spontaneous conception. WHAT IS KNOWN ALREADY: Women who conceive using IVF treatment can experience higher levels of pregnancy-specific distress and are at increased risk of pre-eclampsia, an immune-related condition which in turn has been linked to PPP, as well as other pregnancy and delivery complications, which also serve as PPP risk factors. It is not known whether the risk of PPP is increased in women who have conceived using IVF treatment. STUDY DESIGN, SIZE, DURATION: A nationwide, register-based, case-control study of all primiparous women who had given birth after IVF treatment between 1988 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information about 10 412 women was collected from the Swedish IVF register. A control group of women who had given birth after spontaneous conception was selected from the Swedish Medical Birth Register (n = 18 624). PPP diagnoses, identified using ICD-10 diagnostic codes F20-31 and F531 the first year postpartum, were collected from the National Patient Register. Associations between PPP and IVF/spontaneous conception were evaluated using chi-square tests and logistic regression analyses while controlling for known risk factors of PPP. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in PPP prevalence between the IVF group and the control group (0.3%, n = 29 versus 0.4%, n = 77) in the chi-square analysis (P = 0.169) or the multiple logistic regression analyses (P = 0.646; odds ratio (OR): 1.178; 95% CI: 586-2.365). No associations between pregnancy or delivery complications and PPP were found. A history of any psychiatric disorder (P < 0.001; OR = 40.7; 95% CI = 23.9-69.5), or specifically a psychotic (P < 0.001; OR = 324.1; 95% CI = 131.3-800.0), bipolar (P < 0.001; OR = 516.1; 95% CI = 264.3-1008.1), depressive (P < 0.001; OR = 27.5; 95% CI = 16.2-46.5), anxiety (P < 0.001; OR = 12.9; 95% CI = 7.4-22.6) or personality disorder (P < 0.001; OR = 27.3; CI = 11.8-63.0), all significantly increased the risk of PPP. LIMITATIONS REASONS FOR CAUTION: PPP is a rare condition, hence the number of individuals was small. Since all women for whom information was available from all registers were included, it was not possible to further increase the power of the study using this design. WIDER IMPLICATIONS OF THE FINDINGS: Since this study is the first to examine risk of PPP after IVF treatment, more studies are needed to verify these results. The generalizability is restricted to primiparous women in western countries. This study confirms the results of previous studies in showing a history of mental illness to be the major risk factor for PPP. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: Not applicable.

Mental health after first childbirth in women requesting a caesarean section; a retrospective register-based study.

BACKGROUND: Psychiatric illness before delivery increases the risk of giving birth by caesarean section on maternal request (CSMR) but little is known about these women's mental health after childbirth. In this study we aimed to compare the prevalence of psychiatric disorders five years before and after delivery in primiparae giving birth by CS on maternal request to all other primiparae giving birth, indifferent on their mode of delivery. METHODS: The study population comprised all women born in Sweden 1973-1983 giving birth for the first time in 2002-2004. Psychiatric diagnoses, in- and outpatient care were retrieved from the National Patient Register in Sweden. The risk of psychiatric care after childbirth was estimated using CSMR, previous mental health and sociodemographic variables as covariates. RESULTS: Psychiatric disorders after childbirth were more common in women giving birth by CSMR compared to the other women (11.2% vs 5.5%, p < 0.001). CSMR increased the risk of psychiatric disorders after childbirth (aOR 1.5, 95% CI 1.2-1.9). The prevalence of psychiatric disorders had increased after compared to before childbirth (mean difference 0.02 ± 0.25, 95% CI 0.018-0.022, p < 0.001). Women giving birth by CSMR tended to be diagnosed in the inpatient care more often (54.9% vs. 45.8%, p = 0.056) and were more likely to have been diagnosed before childbirth as well (39.8% vs. 24.2%, p < 0.001). CONCLUSIONS: Women giving birth by CSMR more often suffer from psychiatric disorders both before and after delivery. This indicates that these women are a vulnerable group requiring special attention from obstetric- and general health-care providers. This vulnerability should be taken into account when deciding on mode of delivery.

Incidence of Perthes' disease in children born between 1973 and 1993.

Background and purpose - The incidence of Perthes' disease as reported in the literature varies widely between and within countries. The etiology of the disease is still unknown. Both environmental and genetic factors have been suggested to play a part in either causing the disease or increasing the susceptibility of an individual. We determined the incidence of Perthes' disease in Sweden and investigated possible relationships to parental socioeconomic status, ethnicity, marital status, mothers' age when giving birth, parity, number of siblings, and smoking habits. Patients and methods - Six Swedish population-based registers were used, together covering all children born in Sweden from 1973 through 1993. Results - The incidence of Perthes' disease in Sweden was 9.3 per 100,000 subjects. The ratio between boys and girls was 3.1:1. The educational level of the father and the mother of a child with Perthes' disease was lower than in the controls. The incidence was lower when the fathers were in the highest income bracket (above the 90th percentile). A higher proportion of parents of Nordic lineage had children with Perthes' disease than parental pairs with one or both who were not of such lineage. Interpretation - This study confirms that there is an association between the incidence of Perthes' disease and the socioeconomic status of the parents.

Postpartum depressive symptoms and its association to daytime sleepiness and restless legs during pregnancy.

BACKGROUND: Postpartum depression is a common condition, which consequences might be harmful for both mother and child. Since sleep and depression are closely related it is possible that women who suffer from sleep related problems during pregnancy are more likely to develop depression in the postpartum period. This study aims to investigate the possible association between depressive symptoms in the postpartum period and sleep related problems during pregnancy. METHODS: In this study 293 women in the last trimester of pregnancy answered a questionnaire about symptoms of restless legs, snoring and daytime sleepiness. They also completed the Epworth Sleepiness Scale (ESS). The same women were screened for depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) four to ten weeks after giving birth. Additional information about social data, pregnancy and delivery was received from the medical charts. RESULTS: Women with postpartum depressive symptoms had higher prevalence of excessive daytime sleepiness defined as ESS score ≥10 (OR 3.84, CI 1.57-9.39), and restless legs syndrome (OR 2.837 CI 1.18-6.84) in last trimester of pregnancy, when adjusted for socio-demographic factors and obstetric risk factors. No association was found between postpartum depressive symptoms and snoring. CONCLUSIONS: Depressive symptoms after childbirth are preceded by sleep related problems such as daytime sleepiness and restless legs, already during pregnancy. The results from Epworth Sleepiness Scale and a questionnaire concerning Restless Legs Syndrome completed during pregnancy might be a valuable contribution for detecting women at risk for postpartum depression, enabling preventive interventions.

Effect of maternal stress during pregnancy on the risk for preterm birth.

BACKGROUND: Preterm birth defined as birth prior to 37 weeks of gestation is caused by different risk factors and implies an increased risk for disease and early death for the child. The aim of the study was to investigate the effect of maternal stress during pregnancy on the risk of preterm birth. METHODS: A case-control study that included 340 women; 168 women who gave birth preterm and 172 women who gave birth at term. Data were manually extracted from standardized medical records. If the medical record contained a psychiatric diagnosis or a self-reported stressor e.g., depression or anxiety the woman was considered to have been exposed to stress during pregnancy. Adjusted odds ratio (AOR) was used to calculate the attributable risk (AR) of maternal stress during pregnancy on preterm birth, both for the women exposed to stress during pregnancy (AR1 = (AOR-1)/AOR) and for the whole study population (AR2 = AR1*case fraction). RESULTS: Maternal stress during pregnancy was more common among women who gave birth preterm compared to women who gave birth at term (p <0.000, AOR 2.15 (CI = 1.18-3.92)). Among the women who experienced stress during pregnancy 54% gave birth preterm with stress as an attributable risk factor. Among all of the women the percentage was 23%. CONCLUSIONS: Stress seems to increase the risk of preterm birth. It is of great importance to identify and possibly alleviate the exposure to stress during pregnancy and by doing so try to decrease the preterm birth rate.

Sleepiness and sleep-disordered breathing during pregnancy.

PURPOSE: This study aimed to examine if there is a difference in the prevalence of obstructive sleep apnea (OSA) and sleepiness between pregnant and non-pregnant women. It also aimed to evaluate if obstetric outcomes were associated to sleep-disordered breathing among the pregnant women. METHODS: One hundred pregnant women (gestational weeks 24-34) and 80 age- and body mass index-matched non-pregnant women underwent whole-night respiratory recordings (airflow, snoring, respiratory movements, body position, pulse oximetry). The women also answered a questionnaire including the Epworth sleepiness scale. RESULTS: Eighty-nine percent of the pregnant women had normal body mass index (BMI). Objectively, recorded snoring was more common among the pregnant women (median 9 % of total estimated sleep time) than among the controls (4 % of total sleep time, p = 0.005). Three of the pregnant women had OSA (apnea/hypopnea index (AHI) >5), but in two cases, this was mainly due to central hypopneas. None had AHI >10. Two controls were diagnosed as OSA. Respiratory parameters including snoring showed no impact on obstetric outcomes. Total Epworth sleepiness scale (ESS) score was higher among pregnant women than among controls (median 9 vs 7, p < 0.001). There was no difference concerning the separate items. There were no significant associations between either subjectively reported or objectively recorded snoring and ESS scores. CONCLUSION: There was no increased prevalence of obstructive sleep apnea among pregnant women. One reason for this could be that the majority of the women in this study were non-obese. Neither OSA nor snoring was likely an explanation for the increased daytime sleepiness seen in the pregnant women.

Caesarean section per se does not increase the risk of offspring developing type 1 diabetes: a Swedish population-based study.

AIMS/HYPOTHESIS: Some studies have revealed a relationship between Caesarean section (CS) and type 1 diabetes, while other studies have not. By using the Swedish paediatric quality register we investigated whether birth by CS is related to the risk of developing type 1 diabetes during childhood. METHODS: All children diagnosed with type 1 diabetes from 2000 to 2012 and included in the register (n = 9,376) were matched with four controls by year, day of birth, sex and county of birth from the Swedish Medical Birth Register. RESULTS: Overall, 13.5% of deliveries were by CS. By group, 14.7% of children who developed type 1 diabetes were delivered by CS compared with 13.3% of control children (p < 0.001). Mothers with diabetes more often gave birth by CS than mothers without diabetes (78.8% vs 12.7%, p < 0.001). In a logistic regression model adjusting for maternal age, maternal diabetes and BMI in early pregnancy, the OR for CS was 1.0. A child who developed type 1 diabetes and had a mother with type 1 diabetes at the time of delivery had the highest OR to have been born by CS. Children of mothers without diabetes, delivered by CS, had no increased risk of developing type 1 diabetes. Maternal diabetes was the strongest predictor of childhood diabetes (OR 3.4), especially if the mother had type 1 diabetes (OR 7.54). CONCLUSIONS/INTERPRETATION: CS had no influence on the risk of type 1 diabetes during childhood or adolescence. However, maternal diabetes itself strongly increased the risk of offspring developing type 1 diabetes.

Effects of continuous midwifery labour support for women with severe fear of childbirth.

BACKGROUND: Continuous support by a midwife during childbirth has shown positive effects on the duration of active labour, use of pain relief and frequency of caesarean section (CS) in women without fear of childbirth (FOC). We have evaluated how continuous support by a specially assigned midwife during childbirth affects birth outcome and the subjective experience of women with severe FOC. METHODS: A case-control pilot study with an index group of 14 women with severe FOC and a reference group of 28 women without FOC giving birth. In this study the index group received continuous support during childbirth. RESULTS: The women with severe FOC more often had an induction of labour. The parous women with severe FOC had a shorter duration of active labour compared to the parous reference women (p = 0.047). There was no difference in caesarean section frequency between the two groups. Women with severe FOC experienced a very high anxiety level during childbirth (OR = 20.000, 95% CI: 3.036-131.731). CONCLUSION: Women with severe FOC might benefit from continuous support by a midwife during childbirth. Midwives should acknowledge the importance of continuous support in order to enhance the experience of childbirth in women with severe FOC.

Intergenerational Cohort Study of Preterm and Small-for-Gestational-Age Birth in Twins and Singletons.

To date, several studies have investigated the intergenerational effect of preterm and small-for-gestational-age (SGA) births. However, most studies excluded both twin mothers and twin offspring from the analyses. Thus, the objective of this study was to investigate the intergenerational effect of preterm birth and SGA births among twins and singletons. A prospective population-based register study of mother-firstborn offspring pairs recorded in the Swedish Medical Birth Register was performed. The study included 4,073 twins and 264,794 singletons born from 1973-1983 and their firstborns born from 1986-2009. Preterm birth was defined as birth at <37 weeks of gestation, and SGA as birth weight <2 standard deviations of the Swedish standard. Logistic regressions were performed to estimate the intergenerational effect of each birth characteristic. Adjustments were made for maternal grandmothers' and mothers' socio-demographic factors, in addition to maternal birth characteristics. Among mothers born as singletons, being born preterm was associated with an increased risk of delivering a preterm child (adjusted odds ratio (OR) 1.39, 95% Confidence Interval (CI) = 1.29-1.50), while being born SGA increased the likelihood of having an SGA child (adjusted OR 3.04, 95% CI = 2.80-3.30) as well as a preterm child (adjusted OR 1.30, 95% CI = 1.20-1.40). In twin mothers, the corresponding ORs tended to be lower, and the only statistically significant association was between an SGA mother and an SGA child (adjusted OR 2.15, 95% CI = 1.40-3.31). A statistically significant interaction between twinning and mother's size for gestational age was identified in a multivariate linear regression analysis, indicating that singleton mothers born SGA were associated with a lower birth weight compared with mothers not born SGA. Preterm birth and SGA appear to be transferred from one generation to the next, although not always reaching statistical significance. These effects seem to be less evident in mothers born as twins compared with those born as singletons.

Maternal obesity and risk of Down syndrome in the offspring.

OBJECTIVE: The objective of this article is to determine if maternal obesity is associated with an increased risk of Down syndrome in the offspring and whether the risk estimates for trisomy 21 based on combined screening is affected by maternal body mass index (BMI). METHODS: Study group I consisted of a nationwide cohort of 1 568 604 women giving birth; outcome was infants born with Down syndrome [Correction made here after initial online publication.]. Adjustment was made for maternal age. Study group II consisted of 10 224 women undergoing 1st trimester combined screening. Outcome was risk assessment for Down syndrome. All women were divided into six BMI groups, and outcomes were evaluated over the BMI strata with BMI 18.5 to 24.9 as reference and correcting for maternal age. RESULTS: Obese women had an increased risk for giving birth to an infant with Down syndrome compared with normal-weight women, BMI 30 to 34.9 odds ratio (OR) 1.31 [95% confidence interval (CI) 1.10-1.55], BMI 35 to 39.9 OR 1.12 (95% CI 0.82-1.53), BMI ≥ 40 OR 1.56 (95% CI 1.00-2.43). The observed and the expected numbers of women with a risk of Down syndrome >1/300 based on 1st trimester combined screen and maternal age were similar in each BMI group. CONCLUSION: Maternal obesity seems to increase the risk for Down syndrome births. The risk estimate for Down syndrome with 1st trimester combined screening is unaffected by BMI.

Snoring during pregnancy and its relation to sleepiness and pregnancy outcome - a prospective study.

BACKGROUND: The incidence of snoring and sleepiness is known to increase during pregnancy, and this might impact maternal health and obstetric outcome. However, the association between snoring and sleepiness during pregnancy is not fully understood. This study was aimed at investigating the development of snoring during pregnancy and prospectively assessing if there is an association between snoring and sleepiness or adverse pregnancy outcomes, such as preeclampsia, mode of delivery, and fetal complications. METHODS: Consecutively recruited pregnant women (n = 500) received a questionnaire concerning snoring and sleep at the 1st and 3rd trimester of pregnancy. The women who had rated their frequency of snoring at both occasions (n = 340) were divided into subgroups according to the development of snoring they reported and included in the subsequent analyses. Additional medical data were collected from the medical records. RESULTS: The frequency of snoring was 7.9% in the 1st trimester and increased to 21.2% in the 3rd trimester of pregnancy. The women who snored already in early pregnancy had significantly higher baseline BMI (p = 0.001) than the women who never snored, but snoring was not associated with the magnitude of weight gain during pregnancy. Snoring women were more likely to experience edema in late pregnancy than the non-snorers. Women who started to snore during pregnancy had higher Epworth Sleepiness Scores than the non snorers in both early and late pregnancy. No significant association between obstetric outcome and snoring was found. CONCLUSION: Snoring does increase during pregnancy, and this increase is associated with sleepiness, higher BMI at the start of pregnancy and higher prevalence of edema, but not with weight gain.