Male patients with inflammatory joint diseases are less likely than controls to be childless: results from a Norwegian population-based cohort study of 10 865 patients.

OBJECTIVES: To investigate the number of children per man and the proportion of childless men as a proxy of fertility in a national cohort of men with inflammatory joint diseases (IJDs), compared with matched controls from the general population. METHODS: This is a nationwide, population-based retrospective cohort study. Male patients with IJDs (n = 10 865) in the Norwegian Arthritis Registry were individually matched 1:5 on birth year and county of residence with men without IJDs obtained from the National Population Register (n = 54 325). Birth data were obtained from the Medical Birth Registry of Norway. We compared the mean number of children per man and the proportion of childless men and analysed the impact of age and year of diagnosis. RESULTS: The mean number of children per man in the patient group was 1.80 versus 1.69 in the comparison group (p <0.001), and 21% of the patients in the patient group were childless versus 27% in the comparison group (p <0.001). The finding of less childlessness and higher number of children per man remained consistent across age at diagnosis, except for those diagnosed at age 0-19 years. The difference in childlessness was most pronounced for men diagnosed after year 2000, especially when diagnosed at 30-39 years of age (22% vs 32%, p<0.001). CONCLUSION: In this large cohort study we found that patients with IJD have a higher number of children and are less likely to be childless compared with controls. Factors associated with developing or having an IJD might influence fertility and this requires further investigation.

Time trends in perinatal outcomes among HIV-positive pregnant women in Northern Tanzania: A registry-based study.

INTRODUCTION: Maternal HIV infection is associated with increased risk of having a preterm delivery, low birth weight baby, small for gestational age baby and stillbirth. Maternal use of combination antiretroviral treatment is also associated with preterm delivery and low birth weight, although the effects vary by the type of drugs and timing of initiation. OBJECTIVE: To examine time trends in adverse perinatal outcomes among HIV-positive compared with HIV-negative women. DESIGN: Registry-based cohort study. SETTING: Northern Tanzania, 2000-2018. STUDY SAMPLE: Mother-baby pairs of singleton deliveries (n = 41 156). METHODS: Perinatal outcomes of HIV-positive women were compared with HIV-negative women during time periods representing shifts in prevention of mother-to-child transmission guidelines. Monotherapy was used as first-line therapy before 2007 while combination antiretroviral treatment was routinely used from 2007. Log binomial and quantile regression were used to analyze the data. MAIN OUTCOME MEASURES: Preterm delivery, low birth weight, perinatal death, stillbirth, low Apgar score, transfer to neonatal care unit and small for gestational age. RESULTS: Overall, maternal HIV infection was associated with a higher risk of low birth weight and small for gestational age. Moreover, this pattern became more pronounced over time for low birth weight, the last time period being an exception. For other outcomes we found none or only a small overall association with maternal HIV infection, although a trend towards higher risk over time in HIV-positive compared with HIV-negative women was observed for preterm delivery and perinatal death. Quantile regression showed an increase in birth weight in babies born to HIV-negative women over time and a corresponding decline in birth weight in babies born to HIV-positive women. CONCLUSION: Unfavourable trends in some of the selected perinatal outcomes were seen for HIV-positive compared with HIV-negative women. Potential side-effects of combination antiretroviral treatment in pregnancy should be further explored.

Childbirth delivery mode and the risk of multiple sclerosis: a prospective population-based study.

BACKGROUND: Caesarean section (CS) may affect the risk of developing multiple sclerosis (MS) in the offspring, possibly through changes in gut microbiota composition, but findings from previous studies are inconsistent. We investigated whether birth by CS was associated with the risk of adult-onset MS. METHODS: We conducted a prospective population-based cohort study, including all individuals born in Norway between 1967 and 2003, using the Medical Birth Registry of Norway linked with the Norwegian Multiple Sclerosis Registry and Biobank. The follow-up was until 2021. We used multivariable Cox models to estimate HRs for MS risk with 95% CIs. RESULTS: Among 2 046 637 individuals in the cohort, 4954 MS cases were identified. Being born by CS was associated with a modest increase in MS risk (HR=1.18, 95% CI 1.05 to 1.32). In the sibling-matched analysis, we found no association between CS and MS risk. We found an interaction between CS and gestational age (p=0.03): CS was associated with an increased risk of MS in individuals born preterm (HR=1.62, 95% CI 1.18 to 2.24), whereas there was no association in individuals born at term (HR=1.13, 95% CI 0.99 to 1.27). In a subgroup analysis of individuals born in 1988 and onwards, emergency CS was related to an elevated MS risk (HR=1.40, 95% CI 1.07 to 1.83), whereas planned CS was not (HR: 1.10, 95% CI 0.77 to 1.58). CONCLUSIONS: CS was associated with a modestly higher risk of developing MS. However, the stronger associations seen in subgroups who likely experienced a more complicated pregnancy/delivery may point to confounding underlying these associations.

Prenatal exposure to pregabalin, birth outcomes and neurodevelopment - a population-based cohort study in four Nordic countries.

INTRODUCTION: Pregabalin is an antiepileptic drug frequently prescribed to pregnant women. Risks of adverse birth and postnatal neurodevelopmental outcomes following prenatal exposure to pregabalin are uncertain. OBJECTIVE: To investigate the association between prenatal exposure to pregabalin and the risks of adverse birth and postnatal neurodevelopmental outcomes. METHODS: This study was conducted using population-based registries in Denmark, Finland, Norway, and Sweden (2005-2016). We compared pregabalin exposure against no exposure to antiepileptics and against active comparators lamotrigine and duloxetine. We obtained pooled propensity score-adjusted estimates of association using fixed-effect and Mantel-Haenszel (MH) meta-analyses. RESULTS: The total number of pregabalin-exposed births was 325/666,139 (0.05%) in Denmark, 965/643,088 (0.15%) in Finland, 307/657,451 (0.05%) in Norway, and 1275/1,152,002 (0.11%) in Sweden. The adjusted prevalence ratios (aPRs) with 95% confidence interval (CI) following pregabalin exposure versus no exposure were 1.14 (0.98-1.34) for major congenital malformations and 1.72 (1.02-2.91) for stillbirth, which attenuated to 1.25 (0.74-2.11) in MH meta-analysis. For the remaining birth outcomes, the aPRs were close to or attenuated toward unity in analyses using active comparators. Adjusted hazard ratios (95% CI) contrasting prenatal pregabalin exposure versus no exposure were 1.29 (1.03-1.63) for ADHD and attenuated when using active comparators, 0.98 (0.67-1.42) for autism spectrum disorders, and 1.00 (0.78-1.29) for intellectual disability. CONCLUSIONS: Prenatal exposure to pregabalin was not associated with low birth weight, preterm birth, small for gestational age, low Apgar score, microcephaly, autism spectrum disorders, or intellectual disability. On the basis of the upper value of the 95% confidence interval, increased risks greater than 1.8 were unlikely for any major congenital malformation and ADHD. For stillbirth and most groups of specific major congenital malformations, the estimates attenuated in MH meta-analysis.

Maternal antiretroviral treatment for HIV infection and risk of small-for-gestational-age birth: A systematic review and meta-analysis of protease inhibitor-based treatment and timing of treatment.

BACKGROUND: Data indicate that certain combination antiretroviral treatment (cART) regimens, particularly protease inhibitor (PI)-based regimens, and cART initiation before conception may be associated with adverse pregnancy outcomes. The risk of having a small-for-gestational-age (SGA) infant was examined among pregnant HIV-infected mothers on 1) PI-based compared to non-PI-based cART, and 2) any cART initiated before compared to after conception. METHODS: A search was conducted using PubMed, Embase, and the Cochrane Library, and a systematic review was performed of studies published since Dec 1, 1995. Effect estimates with 95% confidence intervals (CIs) were extracted and meta-analyses with random-effects models were conducted. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. FINDINGS: Of 783 identified studies, 28 fulfilled the inclusion criteria. Meta-analysis indicated that PI-based cART was associated with a possible slightly increased risk of SGA compared with non-PI-based cART (pooled odds ratio [OR]: 1·09; CI: 0·76, 1·55). Initiation of cART before conception was also associated with a possible slightly increased risk of SGA compared with after conception (pooled OR: 1·08; CI: 0·95, 1·22). The overall certainty of evidence was very low and low for the first and second research questions, respectively. INTERPRETATION: Although the benefits of cART largely outweigh the risks, these findings indicate the possibility of slightly increased risks of having an SGA infant. This indicates that careful monitoring of fetuses exposed to PI-based cART or cART before pregnancy might be reasonable. Based on the uncertainty of evidence, further research may change this conclusion.

Is the risk of cardiovascular disease in women with pre-eclampsia modified by very low or very high offspring birth weight? A nationwide cohort study in Norway.

OBJECTIVES: To examine whether the risk of cardiovascular disease (CVD) in women with pre-eclampsia is modified by very low or very high offspring birth weight. Further, we studied whether diabetes in pregnancy modified this risk. DESIGN: Nationwide cohort study. SETTING: Norwegian population registries. PARTICIPANTS: 618 644 women who gave birth to their first child during 1980-2009. METHODS: The women were followed from delivery until the development of CVD or censoring, by linkage of the Medical Birth Registry of Norway to the Cardiovascular Disease in Norway project, and the Norwegian Cause of Death Registry. PRIMARY OUTCOME MEASURE: CVD. RESULTS: Compared with normotensive women with normal offspring birth weight, women with pre-eclampsia had increased risk of CVD (HR 2.16; 95% CI 2.05 to 2.26). The CVD risk was even higher when pre-eclampsia was accompanied with a large for gestational age offspring (LGA, z-score >2.0) (HR 2.57; 95% CI 2.08 to 3.18). Women with pre-eclampsia and a small for gestational age offspring (SGA, z-score <-2.0) had an HR of 1.54 (95% CI 1.23 to 1.93) compared with normotensive women with normal offspring birth weight.Also, women with diabetes had increased CVD risk, but no additional risk associated with an LGA or SGA offspring. CONCLUSIONS: Women with pre-eclampsia and an LGA offspring had higher risk of CVD than pre-eclamptic women with a normal weight (z-score -2.0 to 2.0) or SGA offspring. These findings suggest that factors causing pre-eclampsia and an LGA offspring are also linked to development of CVD.

Association of adverse childhood experiences with the development of multiple sclerosis.

OBJECTIVE: To study whether exposure to childhood emotional, sexual or physical abuse is associated with subsequent multiple sclerosis (MS) development. METHODS: A nationwide, prospective cohort study based on participants in the Norwegian Mother, Father and Child cohort study. Enrolment took place 1999-2008, with follow-up until 31 December 2018. Childhood abuse before age 18 years was obtained from self-completed questionnaires. We identified MS diagnoses through data-linkage with national health registries and hospital records. The Cox model was used to estimate HRs for MS with 95% CIs, adjusting for confounders and mediators. RESULTS: In this prospective cohort study, 14 477 women were exposed to childhood abuse and 63 520 were unexposed. 300 women developed MS during the follow-up period. 71 of these (24%) reported a history of childhood abuse, compared with 14 406 of 77 697 (19%) women that did not develop MS. Sexual abuse (HR 1.65, 95% CI 1.13 to 2.39) and emotional abuse (HR 1.40, 95% CI 1.03 to 1.90) in childhood were both associated with an increased risk of developing MS. The HR of MS after exposure to physical abuse was 1.31 (95% CI 0.83 to 2.06). The risk of MS was further increased if exposed to two (HR 1.66, 95% CI 1.04 to 2.67) or all three abuse categories (HR 1.93, 95% CI 1.02 to 3.67). INTERPRETATION: Childhood sexual and emotional abuse were associated with an increased risk of developing MS. The risk was higher when exposed to several abuse categories, indicating a dose-response relationship. Further studies are needed to identify underlying mechanisms.

Vitamin B status and association with antiseizure medication in pregnant women with epilepsy.

OBJECTIVE: Antiseizure medication (ASM) use interacts with vitamin B status in nonpregnant epilepsy populations. We aimed to examine the association between ASM and vitamin B status in pregnant women with epilepsy. METHODS: We performed a cross-sectional study of pregnancies in women with epilepsy enrolled in the Norwegian Mother, Father and Child Cohort Study from 1999 to 2008. Data on ASM and vitamin supplement use were collected from questionnaires. We analyzed maternal plasma concentrations of ASM and metabolites of folate, including unmetabolized folic acid (UMFA), riboflavin (vitamin B2), pyridoxine (vitamin B6), and niacin (vitamin B3) during gestational weeks 17-19. RESULTS: We included 227 singleton pregnancies exposed to ASM with available plasma samples (median maternal age 29 years, range 18 to 41 years). From the preconception period to gestational week 20, any supplement of folic acid was reported in 208 of pregnancies (94%), riboflavin in 72 (33%), pyridoxine in 77 (35%), and niacin in 45 (20%). High ASM concentrations correlated with high concentrations of UMFA and inactive folate metabolites, and with low concentrations of riboflavin and metabolically active pyridoxine. There was no association between ASM and niacin status. SIGNIFICANCE: ASM concentrations during pregnancy were associated with vitamin B status in pregnant women with epilepsy. Additional studies are needed to determine the clinical impact of these findings, and to define the optimal vitamin doses that should be recommended to improve pregnancy outcomes.

Exposure to breastfeeding and risk of developing multiple sclerosis.

BACKGROUND: Early-life factors are reported to modulate the risk of developing multiple sclerosis (MS) among adults. The association between exposure to breastfeeding and the risk of MS is debated. We aimed to disclose whether past exposure to breastfeeding and its duration are associated with the risk of developing MS. METHODS: We used a cohort design linking prospectively collected information on breastfeeding from the Cohort of Norway community-based surveys on health status (CONOR) with the Norwegian MS Registry and the population-based Medical Birth Registry of Norway that includes information on all births in Norway since 1967. MS clinical onset was collected throughout 2016. A total of 95 891 offspring born between 1922 and 1986 to mothers participating in CONOR were included. We identified 215 offspring within this cohort who developed adult-onset MS. Associations between breastfeeding and MS risk were estimated as hazard ratios using Cox proportional hazard models adjusting for maternal factors including education. RESULTS: We found no association between having been breastfed for ≥4 months and MS risk, also after adjusting for various maternal factors (hazard ratio = 0.90; 95% confidence interval 0.68-1.19). The estimates did not change for different durations of breastfeeding. The results were similar when adjusting for other perinatal factors. CONCLUSION: Our study could not confirm previous findings of an association between breastfeeding and risk of MS. Breastfeeding information was less likely to be biased by knowledge of disease compared with case-control studies.

Heart Failure in Women With Hypertensive Disorders of Pregnancy: Insights From the Cardiovascular Disease in Norway Project.

Hypertensive disorders of pregnancy (HDP) have been associated with heart failure (HF). It is unknown whether concurrent pregnancy complications (small-for-gestational-age or preterm delivery) or recurrent HDP modify HDP-associated HF risk. In this cohort study, we included Norwegian women with a first birth between 1980 and 2004. Follow-up occurred through 2009. Cox models examined gestational hypertension and preeclampsia in the first pregnancy as predictors of a composite of HF-related hospitalization or HF-related death, with assessment of effect modification by concurrent small-for-gestational-age or preterm delivery. Additional models were stratified by final parity (1 versus ≥2 births) and tested associations with recurrent HDP. Among 508 422 women, 565 experienced incident HF over a median 11.8 years of follow-up. After multivariable adjustment, gestational hypertension in the first birth was not significantly associated with HF (hazard ratio, 1.41 [95% CI, 0.84-2.35], P=0.19), whereas preeclampsia was associated with a hazard ratio of 2.00 (95% CI, 1.50-2.68, P<0.001). Among women with HDP, risks were not modified by concurrent small-for-gestational-age or preterm delivery (Pinteraction=0.42). Largest hazards of HF were observed in women whose only lifetime birth was complicated by preeclampsia and women with recurrent preeclampsia. HF risks were similar after excluding women with coronary artery disease. In summary, women with preeclampsia, especially those with one lifetime birth and those with recurrent preeclampsia, experienced increased HF risk compared to women without HDP. Further research is needed to clarify causal mechanisms.

Maternal outcome after complete uterine rupture.

INTRODUCTION: Complete uterine rupture, a rare peripartum complication, is often associated with a catastrophic outcome for both mother and child. However, few studies have investigated large datasets to evaluate maternal outcomes after complete ruptures, particularly in unscarred uteri. This paucity of studies is partly due to the rarity of both the event and the serious outcomes, such as peripartum hysterectomy and maternal death. The incidence of uterine rupture is expected to increase, due to increasing cesarean section rates worldwide. Thus, it is important to have more complete knowledge about the immediate maternal outcome following a complete uterine rupture. The objective was to identify maternal outcomes and their risk factors following complete uterine ruptures. MATERIAL AND METHODS: This was a population-based study using data from the Medical Birth Registry of Norway, the Patient Administration System and medical records. Maternities with complete uterine rupture after start of labor in Norway during 1967-2008 (n = 247 births), identified among 2 209 506 women. Uterine ruptures were identified from both registries and were further studied through a review of medical records. Only complete ruptures were included in analysis. The associations between maternal outcomes and demographic and labor risk factors were estimated. Odds ratios (ORs) were determined with crude logistic regressions for each risk factor. Separate multivariable logistic regressions were performed to calculate adjusted odds ratios and 95% confidence intervals (CIs). RESULTS: We identified 88 (35.6%) healthy mothers, 107 (43.3%) severe postpartum hemorrhages without hysterectomy, 51 (20.6%) peripartum hysterectomies, and three (1.2%) maternal deaths. Peripartum hysterectomy decreased significantly in the last years of study. Unscarred uterine ruptures significantly increased the risk of peripartum hysterectomy compared with scarred uterine ruptures (AOR 2.6, 95% CI 1.3-5.3). Other factors that increased the risk of peripartum hysterectomy following rupture were: maternal age ≥35 years (AOR 2.3, 95% CI 1.1-5.0), parity ≥3 vs parity 1-2 (AOR 2.8, 95% CI 1.2-6.7), and rupture detection after vaginal delivery (AOR 2.2, 95% CI 1.1-4.8). CONCLUSIONS: Unscarred uteri, older maternal age, parity ≥3, and rupture detection after vaginal delivery showed the highest associations with the risk of peripartum hysterectomy after complete uterine rupture.

Hypertensive pregnancy disorders increase the risk of maternal cardiovascular disease after adjustment for cardiovascular risk factors.

BACKGROUND AND AIM: Hypertensive pregnancy disorders are associated with subsequent cardiovascular disease (CVD), but the extent to which this association is explained by shared risk factors is unknown. We aimed to evaluate whether hypertensive pregnancy disorder in first pregnancy is associated with increased subsequent risk of maternal CVD after adjustment for established CVD risk factors measured after pregnancy. METHODS AND RESULTS: A total of 20,075 women with a first delivery registered in the Medical Birth Registry of Norway (1980-2003) participated in Cohort of Norway (CONOR) health surveys a mean (standard deviation) of 10.7 (5.5) years after delivery. They were then followed (median 11.4 years) for an incident fatal or non-fatal CVD event through linkage to the Cardiovascular Disease in Norway (CVDNOR) database and the Norwegian Cause of Death Registry. Hypertensive pregnancy disorders were associated with an increased risk of CVD [Hazard ratio (HR) 2.3; 95% confidence interval (CI) 1.9-2.8], which remained significant after adjustment for established CVD risk factors including body mass index, smoking, hypertension, diabetes, serum glucose and lipid levels (HR 1.5; 95% CI 1.2-1.8). The population attributable fraction of CVD due to hypertensive pregnancy disorder was 4.3% (95% CI 1.9-6.6) after multivariable adjustment. CONCLUSION: The association between hypertensive pregnancy disorders and CVD risk was mediated in part by related CVD risk factors measured 10 years following delivery. These results underline the importance of post-pregnancy follow-up of women with hypertensive pregnancy disorders focusing on modifiable, lifestyle related risk factors to prevent future CVD.

Correction: Time trends in management of HIV-positive pregnant women in Northern Tanzania: A registry-based study.

[This corrects the article DOI: 10.1371/journal.pone.0184362.].

Verbal abilities in children of mothers with epilepsy: Association to maternal folate status.

OBJECTIVE: To examine the effect of maternal folic acid supplementation and maternal plasma folate and antiepileptic drug (AED) concentrations on language delay in AED-exposed children of mothers with epilepsy. METHODS: Children of mothers with and without epilepsy enrolled from 1999 to 2008 in the Norwegian Mother and Child Cohort study were included. Information on medical history, AED use, and folic acid supplementation during pregnancy was collected from parent-completed questionnaires. Maternal plasma folate and maternal plasma and umbilical cord AED concentrations were measured in blood samples from gestational weeks 17 to 19 and immediately after birth, respectively. Language development at 18 and 36 months was evaluated by the Ages and Stages Questionnaires. RESULTS: A total of 335 AED-exposed children of mothers with epilepsy and 104,222 children of mothers without epilepsy were surveyed. For those with no maternal periconceptional folic acid supplementation, the fully adjusted odds ratio (OR) for language delay in AED-exposed children compared to the controls at 18 months was 3.9 (95% confidence interval [CI] 1.9-7.8, p < 0.001) and at 36 months was 4.7 (95% CI 2.0-10.6, p < 0.001). When folic supplementation was used, the corresponding ORs for language delay were 1.7 (95% CI 1.2-2.6, p = 0.01) and 1.7 (95% CI 0.9-3.2, p = 0.13), respectively. The positive effect of folic acid supplement use on language delay in AED-exposed children was significant only when supplement was used in the period from 4 weeks before the pregnancy and until the end of the first trimester. CONCLUSION: Folic acid use early in pregnancy may have a preventive effect on language delay associated with in utero AED exposure.

Association Between Gestational Hypertension and Risk of Cardiovascular Disease Among 617 589 Norwegian Women.

BACKGROUND: Preeclampsia and gestational hypertension (GH) are the most common hypertensive pregnancy disorders. Preeclampsia has been linked to increased risk of cardiovascular disease (CVD), but a similar association for GH has not been established. We aimed to determine the association between GH and subsequent CVD, and explore the additional role of small-for-gestational-age infants, preterm delivery, and parity. METHODS AND RESULTS: Data from the Medical Birth Registry of Norway were linked to the Cardiovascular Disease in Norway project and the Norwegian Cause of Death Registry. Hazard ratios and 95% confidence intervals were computed using Cox proportional hazard regression, comparing women with and without GH during their first and/or second pregnancy. We included all women with a first delivery from 1980 through 2009 (n=617 589) and followed them for a median of 14.3 (quartile 1-quartile 3: 6.9-21.5) years. Women with GH in the first pregnancy had 1.8-fold (95% confidence interval, 1.7-2.0) higher risk of subsequent CVD compared with women without any hypertensive pregnancy disorder. When GH occurred in combination with small-for-gestational-age infants and/or preterm delivery, the hazard ratio was 2.6 (95% confidence interval, 2.3-3.0). When women with GH were compared with women with preeclampsia, the risk of CVD was comparable when the pregnancy complications occurred in either the first or second pregnancy but was significantly higher for preeclampsia without complications when the disorder occurred in both pregnancies. CONCLUSIONS: GH was associated with increased risk of subsequent CVD, and the highest risk was observed when GH was combined with small-for-gestational-age infants and/or preterm delivery.

Pregnancy-Related Risk Factors Are Associated With a Significant Burden of Treated Hypertension Within 10 Years of Delivery: Findings From a Population-Based Norwegian Cohort.

BACKGROUND: The association between pregnancy complications and women's later cardiovascular disease has, primarily, been evaluated in studies lacking information on important covariates. This report evaluates the prospective associations between pregnancy-related risk factors (preeclampsia/eclampsia, gestational hypertension, pregestational and gestational diabetes mellitus, preterm delivery, and fetal growth restriction) and pharmacologically treated hypertension within 10 years after pregnancy, while adjusting for a wide range of covariates. METHODS AND RESULTS: Prepregnancy normotensive women participating in the MoBa (Norwegian Mother and Child Cohort Study) from January 2004 through July 2009 were linked to the Norwegian Prescription Database to identify women with pharmacologically treated hypertension beyond the postpartum period of 3 months. The burden of hypertension associated with pregnancy-related risk factors was evaluated using an attributable fraction method. A total of 1480 women developed pharmacologically treated hypertension within the follow-up among 60 027 women (rate of hypertension, 3.6/1000 person-years). The proportion of hypertension associated with a history of preeclampsia/eclampsia, gestational hypertension, preterm delivery, and pregestational or gestational diabetes mellitus was 28.6% (95% confidence interval, 25.5%-31.6%) on the basis of multivariable analyses adjusting for numerous covariates. The proportion was similar for women with a healthy prepregnancy body mass index (18.5-24.9 kg/m2; attributable fraction (AF)% 25.9%; 95% confidence interval, 21.3%-30.3%), but considerably higher for nulliparous women at baseline within the first 5 years of follow-up. Small-for-gestational age, however, did not increase subsequent hypertension risk in multivariable analyses. CONCLUSIONS: A structured postpartum follow-up of high-risk women identified through pregnancy-related risk factors would facilitate personalized preventive strategies to postpone or avoid onset of premature cardiovascular events.

Infant outcome after complete uterine rupture.

BACKGROUND: Complete uterine rupture is a rare peripartum complication often associated with a catastrophic outcome for both mother and child. However, little has been written based on large data sets about maternal and infant outcome after complete ruptures. This is partly due to the rarity of the event and the serious maternal and infant outcome; it is also partly due to the use of international diagnostic codes that do not differentiate between the less catastrophic partial rupture and more catastrophic complete uterine rupture. As uterine rupture is expected to increase due to increased cesarean delivery rates worldwide, it is important to know more completely about the outcome following complete uterine rupture. OBJECTIVE: We sought to explore risk factors associated with poor infant outcome in cases of complete uterine rupture. STUDY DESIGN: This population-based study used data from the Medical Birth Registry of Norway, the Patient Administration System, and medical records. We included births with complete uterine rupture after start of labor in all maternity units in Norway during the period 1967 through 2008 (n = 244 births), identified among 2,455,797 births. Uterine ruptures were identified and further studied through a review of medical records. We estimated the associations between infant outcomes and demographic and labor risk factors using logistic regression analyses. Odds ratios with 95% confidence intervals for each risk factor were determined after adjustment for demographic factors and period of birth. The main outcome measure was infant outcome: healthy infant, intrapartum/infant deaths, hypoxic ischemic encephalopathy, and admission to the neonatal intensive care unit. RESULTS: We identified 109 (44.7%) healthy infants, 56 (23.0%) infants needing neonatal intensive care unit admission, 64 (26.2%) intrapartum/infant deaths, and 15 (6.1%) infants with hypoxic ischemic encephalopathy. The highest number of intrapartum/infant deaths occurred in 1967 through 1977 (51.6%) and the fewest in 2000 through 2008 (15.0%). Unscarred uterine ruptures did not significantly increase intrapartum/infant deaths compared to scarred uterine ruptures. Placental separation and/or fetal extrusion had the highest odds ratio for intrapartum/infant deaths (odds ratio, 17.9; 95% confidence interval, 7.5-42.4). Time-to-delivery interval <20 minutes resulted in fewest intrapartum/infant deaths (9.9%), although there were 2 deaths at 10-minute interval. Time to delivery >30 minutes vs <20 minutes increased risk of death (odds ratio, 16.7; 95% confidence interval, 6.4-43.5). CONCLUSION: Intrapartum/infant death after complete uterine rupture decreased significantly over the decades. Time to delivery >30 minutes and placental separation and/or fetal extrusion had the highest association with intrapartum/infant deaths after complete uterine rupture. Time to delivery <20 minutes limited the incidence of intrapartum/infant deaths.

The association between pre pregnancy body mass index and risk of preeclampsia: a registry based study from Tanzania.

BACKGROUND: Preeclampsia is among the leading causes of maternal mortality and morbidity worldwide, occurs in 2-8% of all pregnancies, and is estimated to account for at least 9 % of maternal deaths in Africa. Studies from developed countries show that high pre pregnancy body mass index (BMI) increases the risk of preeclampsia. We examined the association between pre pregnancy BMI and the risk of preeclampsia in Tanzania, a low income country. METHODS: Data from the Kilimanjaro Christian Medical Center (KCMC) Medical Birth Registry recorded between July 2000 and May 2013 were used. We restricted the study population to singleton deliveries among women with no or one previous pregnancy. Pre pregnancy BMI (kg/m2) was categorized according to the WHO categories of underweight (less than 18.5), normal (18.5 - 24.9), overweight (25.0 - 29.9) and obese (30 or more). Potential confounders were adjusted for in multivariable analyses. RESULTS: Among the 17,738 singleton births, 6.6% of the mothers were underweight, 62.1% were of normal BMI, 24.0% were overweight, and 7.3% were obese. Five hundred and eighty-two pregnancies (3.3%) were affected by preeclampsia. Compared to those with normal BMI, overweight and obese women had a higher risk of preeclampsia (aOR (95% CI) 1.4 (1.2 - 1.8) and 1.8 (1.3 - 2.4)), respectively, while underweight women had a lower risk (0.7 (0.4-1.1)). CONCLUSIONS: Pre pregnancy maternal overweight and obesity were associated with an increased risk of preeclampsia in Tanzania. Risks were similar to those reported in high income countries.

Association of Folic Acid Supplementation During Pregnancy With the Risk of Autistic Traits in Children Exposed to Antiepileptic Drugs In Utero.

Importance: Strategies to prevent autism in children exposed to antiepileptic drugs (AEDs) during pregnancy are important. Objective: To explore whether folic acid supplementation and folate status in pregnancy are associated with reduced risk of autistic traits owing to in utero AED exposure. Design, Setting, and Participants: The population-based, prospective Norwegian Mother and Child Cohort Study approached Norwegian-speaking women attending routine ultrasonographic examinations from June 1999 through December 31, 2008 (163 844 of 277 702 women refused). No exclusion criteria were applied beyond language. Questionnaires during and after pregnancy, analysis of blood samples, and linkage to the Medical Birth Registry of Norway were performed. Children aged 18 to 36 months of women with available information on use of AEDs and of folic acid supplementation (n = 104 946) were included in the analysis from March 1, 2016, through June 13, 2017. Exposures: Maternal folic acid supplementation 4 weeks before to 12 weeks after conception. Plasma folate concentration was analyzed at gestational weeks 17 to 19. Main Outcomes and Measures: Autistic traits were evaluated using the Modified Checklist for Autism in Toddlers and Social Communication Questionnaire. Odds ratios (ORs) for autistic traits in children by maternal use vs nonuse of folic acid supplements were adjusted for maternal health and socioeconomic factors. Folate concentrations and folic acid doses were associated with the degree of autistic traits. Results: The overall mean (SD) age of the 104 946 mothers of participating children was 29.8 (4.6) years, with complete information available for analysis in 103 868. Mean (SD) age of women with epilepsy who received AED treatment was 29.4 (4.9); women with epilepsy who did not receive AED treatment, 29.1 (4.9); and without epilepsy, 29.8 (4.6) years. In the 335 children exposed to AEDs, the risk for autistic traits was significantly higher at 18 months of age (adjusted OR [AOR], 5.9; 95% CI, 2.2-15.8) and 36 months of age (AOR, 7.9; 95% CI, 2.5-24.9) when their mothers had not used folic acid supplements compared with children of mothers who had used supplements. Among women without epilepsy, the corresponding risks were lower at 18 months of age (AOR, 1.3; 95% CI, 1.2-1.4) and 36 months of age (AOR, 1.7; 95% CI, 1.5-1.9); among the 389 children of women with untreated epilepsy, the corresponding risks were not significant at 18 months of age (AOR, 1.0; 95% CI, 0.4-3.0) and 36 months of age (AOR, 2.5; 95% CI, 0.4-16.6). Degree of autistic traits was inversely associated with maternal plasma folate concentrations (ß = -0.3; P = .03) and folic acid doses (ß = -0.5; P < .001). Concentrations of AEDs were not associated with the degree of autistic traits. Conclusions and Relevance: Risk of autistic traits in children exposed to AEDs in utero may be mitigated by periconceptional folic acid supplementation and folate status. Fertile women using AEDs should take folic acid supplements continuously.