Mette Christophersen Tollånes

Cesarean Section and Risk of Severe Childhood Asthma: A Population-Based Cohort Study

OBJECTIVE To explore the possible association between delivery by cesarean section (CS) and later development of asthma. STUDY DESIGN A population-based cohort study of 1,756,700 singletons reported to the Medical Birth Registry of Norway between 1967 and 1998, followed up to age 18 years or the year 2002. Exposure was the mode of delivery (spontaneous vaginal, instrumental vaginal, or CS, with planned and emergency CS separately from 1988 onward). Outcome was asthma registered in the National Insurance Scheme, which provides cash benefits to families of children with severe chronic illnesses. We used multivariate Cox proportional hazard models to examine associations between exposure and outcome. RESULTS The cumulative incidence of asthma was 4.0/1000. Children delivered by CS had a 52% increased risk of asthma compared with spontaneously vaginally delivered children (adjusted hazard ratio [HR] = 1.52; 95% confidence interval [CI] = 1.42 to 1.62). Between 1988 and 1998, planned and emergency CS was associated with a 42% (HR = 1.42; 95% CI = 1.25 to 1.61) and 59% (HR = 1.59; 95% CI = 1.44 to 1.75) increased risk of asthma, respectively. CONCLUSION We found a moderately increased risk of asthma in the children delivered by CS. The possibly stronger association with emergency CS compared with planned CS could be worth pursuing to investigate possible causal mechanisms.

Cesarean section and maternal education; secular trends in Norway, 1967-2004.

Background. Worldwide rising cesarean section rates over the past decades have caused much concern. Studies on the association between cesarean section and maternal social background have reported conflicting results. Methods. A cohort study, comprising 837,312 birth order one deliveries notified to the population‐based Medical Birth Registry of Norway during 1967–2004. The relative risk of cesarean section (from 1988 onwards planned and emergency cesarean section) according to maternal educational level was assessed in all deliveries, in an obstetric low‐risk group and within groups of medical/obstetric high‐risk conditions. Results. Throughout the study period, the lowest educated had the highest risk of cesarean section, followed by the medium educational group. In all deliveries, the adjusted relative risk of cesarean section for the lowest versus the highest educated increased from 1.16 (95% CI 1.09–1.23) in the 1967–76 period to 1.34 (95% CI 1.27–1.42) in the 1996–2004 period, and in the obstetric low risk group from 1.19 (95% CI 1.10–1.30) to 1.50 (95% CI 1.38–1.63). From 1988 onwards, the lowest educated had the highest risk of both planned and emergency cesarean section, followed by the medium educational group. Conclusion. The lowest educated had the highest risk of cesarean section, followed by the medium educational group, and the differences gradually increased during 1967–2004. This trend could be accounted for by increasing vulnerability of the lowest educational group due to a strong social migration, and by increased occurrence of cesarean section on maternal request among the lowest educated in recent years.

Familial risk of cerebral palsy: Population based cohort study

Objective To investigate risks of recurrence of cerebral palsy in family members with various degrees of relatedness to elucidate patterns of hereditability. Design Population based cohort study. Setting Data from the Medical Birth Registry of Norway, linked to the Norwegian social insurance scheme to identify cases of cerebral palsy and to databases of Statistics Norway to identify relatives. Participants 2 036 741 Norwegians born during 1967-2002, 3649 of whom had a diagnosis of cerebral palsy; 22 558 pairs of twins, 1 851 144 pairs of first degree relatives, 1 699 856 pairs of second degree relatives, and 5 165 968 pairs of third degree relatives were identified. Main outcome measure Cerebral palsy. Results If one twin had cerebral palsy, the relative risk of recurrence of cerebral palsy was 15.6 (95% confidence interval 9.8 to 25) in the other twin. In families with an affected singleton child, risk was increased 9.2 (6.4 to 13)-fold in a subsequent full sibling and 3.0 (1.1 to 8.6)-fold in a half sibling. Affected parents were also at increased risk of having an affected child (6.5 (1.6 to 26)-fold). No evidence was found of differential transmission through mothers or fathers, although the study had limited power to detect such differences. For people with an affected first cousin, only weak evidence existed for an increased risk (1.5 (0.9 to 2.7)-fold). Risks in siblings or cousins were independent of sex of the index case. After exclusion of preterm births (an important risk factor for cerebral palsy), familial risks remained and were often stronger. Conclusions People born into families in which someone already has cerebral palsy are themselves at elevated risk, depending on their degree of relatedness. Elevated risk may extend even to third degree relatives (first cousins). The patterns of risk suggest multifactorial inheritance, in which multiple genes interact with each other and with environmental factors. These data offer additional evidence that the underlying causes of cerebral palsy extend beyond the clinical management of delivery.

Reduced fertility after cesarean delivery: a maternal choice.

OBJECTIVE: To explore the association between mode of delivery and subsequent fertility. METHODS: Deliveries registered in the Medical Birth Registry of Norway were linked to mothers through national identification numbers. The study population was 596,341 women who had their first delivery during 1967–1996, and who were followed up through 2003. We compared rates of continuation to a subsequent birth according to mode of previous delivery (cesarean compared with vaginal). RESULTS: If the first child survived the first year of life, cesarean delivery was associated with a significantly reduced probability of a second birth (relative risk [RR] 0.82, 95% confidence interval [CI] 0.81–0.83 during 1967–1981, and RR 0.88, 95% CI 0.88–0.89 during 1982–1996). Following a stillbirth or an infant loss, the association was less strong during 1967–1981 (RR 0.93, 95% CI 0.89–0.97) and no longer significant during 1982–1996 (RR 1.00, 95% CI 0.97–1.03). A similar pattern was observed from the second to the third birth and in subgroup analyses of women with preeclampsia or breech presentation and in an obstetric low-risk group. CONCLUSION: Cesarean delivery was more strongly associated with reduced fertility if the infant survived than if it was stillborn or died. This suggests that the reduced fertility was to a large degree voluntary and not related to the indication, nor to any physical consequence, of the cesarean delivery. LEVEL OF EVIDENCE: II

Maternal Prepregnancy BMI and Risk of Cerebral Palsy in Offspring.

OBJECTIVES: To investigate the association between maternal pre-pregnancy BMI and risk of cerebral palsy (CP) in offspring. METHODS: The study population consisted of 188 788 children in the Mothers and Babies in Norway and Denmark CP study, using data from 2 population-based, prospective birth cohorts: the Norwegian Mother and Child Cohort Study and the Danish National Birth Cohort. Prepregnancy BMI was classified as underweight (BMI <18.5), lower normal weight (BMI 18.5–22.9), upper normal weight (BMI 23.0–24.9), overweight (BMI 25.0–29.9), and obese (BMI ≥30). CP diagnoses were obtained from the national CP registries. Associations between maternal prepregnancy BMI and CP in offspring were investigated by using log-binomial regression models. RESULTS: The 2 cohorts had 390 eligible cases of CP (2.1 per 1000 live-born children). Compared with mothers in the lower normal weight group, mothers in the upper normal group had a 40% excess risk of having a child with CP (relative risk [RR], 1.35; 95% confidence interval [CI], 1.03–1.78). Excess risk was 60% (RR, 1.56; 95% CI, 1.21–2.01) for overweight mothers and 60% (RR, 1.55; 95% CI 1.11–2.18) for obese mothers. The risk of CP increased ∼4% for each unit increase in BMI (RR, 1.04; 95% CI, 1.02–1.06). Estimates changed little with adjustment for mother’s occupational status, age, and smoking habits. CONCLUSIONS: Higher prepregnancy maternal BMI was associated with increased risk of CP in offspring.

Pregnancy Outcomes among Female Dental personnel-a registry-based Retrospective Cohort Study

OBJECTIVES The aim of this study was to investigate whether women who have worked as dental personnel in Norway, a group with possible previous exposure to mercury vapor, have had an excess risk of having children with congenital malformations or other adverse pregnancy outcomes compared to the general population. METHODS A cohort of female dental personnel was identified from the archives of the public dental healthcare and the national trade unions in Norway. Data on births and pregnancy outcomes during 1967-2006 were obtained from the Medical Birth Registry of Norway (MBRN). The final cohort of dental personnel consisted of 4482 dental assistants and 1011 dentists. All other women registered in the MBRN were assigned to the control group, in total 1,124,758. Excess risks of several adverse pregnancy outcomes for dental personnel compared to the general population were estimated. Analyses were conducted for the whole time period as well as stratified by 10-year periods. RESULTS Female dental personnel had no observed increased occurrence of congenital malformations (including malformations of the central nervous system, dysplasia of the hip, clubfoot, malformations of the heart and great vessels), low birth weight, preterm birth, small for gestational age, changed gender ratio, multiple birth, stillbirth, or prenatal death. CONCLUSION On a group level, we did not observe any excess risks of congenital malformations or other adverse pregnancy outcomes among female dental personnel in Norway during 1967-2006 compared to the general population.

Porphyrias in Norway

BACKGROUND Porphyria is an umbrella term for a group of largely hereditary diseases that are due to defective haem synthesis. The diseases have a varied and partly overlapping range of symptoms and presentations. The commonest forms of porphyria are porphyria cutanea tarda, acute intermittent porphyria and erythropoietic protoporphyria. The purpose of this study is to provide an overview of the prevalence and pathological manifestations of porphyrias in Norway. MATERIAL AND METHOD Information on all patients registered with the Norwegian Porphyria Centre (NAPOS) up to 2012 was used to estimate the prevalence and incidence of porphyrias in Norway. Figures on symptoms, precipitating factors and follow-up routines were obtained from the Norwegian Porphyria Registry, which includes 70% of Norwegians registered with NAPOS as having porphyria. RESULTS The prevalence of porphyria cutanea tarda was approximately 10 : 100,000 and that of acute intermittent porphyria approximately 4 : 100,000. The total incidence of all porphyrias was approximately 0.5-1 : 100,000 per year. Diagnostic delay, i.e. the time passing between the onset of symptoms and diagnosis, varied from 1-17 years depending on the type of porphyria. There was wide variation in the frequency with which patients with the various types of porphyria went for medical check-ups. INTERPRETATION The prevalence of acute intermittent porphyria and porphyria cutanea tarda appears to be higher in Norway than in most other countries. Data from the Norwegian Porphyria Registry makes it possible to demonstrate differences in treatment and follow-up of porphyria patients and may be used to initiate necessary measures.

Excess risk of adverse pregnancy outcomes in women with porphyria: a population-based cohort study

The porphyrias comprise a heterogeneous group of rare, primarily hereditary, metabolic diseases caused by a partial deficiency in one of the eight enzymes involved in the heme biosynthesis. Our aim was to assess whether acute or cutaneous porphyria has been associated with excess risks of adverse pregnancy outcomes. A population-based cohort study was designed by record linkage between the Norwegian Porphyria Register, covering 70% of all known porphyria patients in Norway, and the Medical Birth Registry of Norway, based on all births in Norway during 1967–2006. The risks of the adverse pregnancy outcomes preeclampsia, delivery by caesarean section, low birth weight, premature delivery, small for gestational age (SGA), perinatal death, and congenital malformations were compared between porphyric mothers and the rest of the population. The 200 mothers with porphyria had 398 singletons during the study period, whereas the 1,100,391 mothers without porphyria had 2,275,317 singletons. First-time mothers with active acute porphyria had an excess risk of perinatal death [adjusted odds ratio (OR) 4.9, 95% confidence interval (CI) 1.5–16.0], as did mothers with the hereditable form of porphyria cutanea tarda (PCT) (3.0, 1.2–7.7). Sporadic PCT was associated with an excess risk of SGA [adjusted relative risk (RR) 2.0, 1.2–3.4], and for first-time mothers, low birth weight (adjusted OR 3.4, 1.2–10.0) and premature delivery (3.5, 1.2–10.5) in addition. The findings suggest women with porphyria should be monitored closely during pregnancy.

Associations of Maternal Atopic Diseases with Adverse Pregnancy Outcomes: a National Cohort Study

BACKGROUND Maternal asthma has been associated with adverse pregnancy outcomes. Little is known about the influence of other atopic diseases on pregnancy outcomes. We assessed how various maternal atopic diseases might affect preterm birth, stillbirth, and neonatal death. METHODS By linking Norwegian national registries, we acquired information on maternal health, socio-demographic factors, pregnancy, birth, and neonatal outcome on all births in Norway from 1967 to 2003. RESULTS A total of 1 974 226 births were included. Of these, 1.8% had a record of maternal asthma, 3.4% of maternal atopic dermatitis, and 0.4% of maternal allergic rhinoconjunctivitis. Overall rates of preterm birth, stillbirth, and neonatal death were 6.0%, 0.6%, and 0.5%, respectively. After adjustments for possible confounders, maternal asthma was associated with increased risk of preterm birth (relative risk (RR), 1.15, [95% confidence interval (CI) 1.10, 1.21]). In contrast, maternal atopic dermatitis was associated with decreased risk of preterm birth (RR 0.90, [95% CI 0.86, 0.93]), stillbirth (RR 0.70, [95% CI 0.62, 0.79]), and neonatal death (RR 0.76, [95% CI 0.65, 0.90]). Similarly, maternal allergic rhinoconjunctivitis was associated with decreased risk of preterm birth (RR 0.84, [95% CI 0.76, 0.94]) and stillbirth (RR 0.40, [95% CI 0.25, 0.66]). CONCLUSIONS We confirmed the previously reported association of maternal asthma with increased risk for preterm birth. Unexpectedly, maternal atopic dermatitis and allergic rhinoconjunctivitis were associated with decreased risk of preterm birth and stillbirth. Mechanisms for these protective associations are unclear, and our findings require confirmation in further studies.

Establishing a network of specialist Porphyria centres - effects on diagnostic activities and services

BackgroundThe porphyrias are a heterogeneous group of rare metabolic diseases. The full spectrum of porphyria diagnostics is usually performed by specialized porphyria laboratories or centres. The European Porphyria Initiative (EPI), a collaborative network of porphyria centres formed in 2001, evolved in 2007 into the European Porphyria Network (EPNET), where participating centres are required to adhere to agreed quality criteria. The aim of this study was to examine the state and distribution of porphyria diagnostic services in 2009 and to explore potential effects of increased international collaboration in the field of these rare diseases in the period 2006–2009.MethodsData on laboratory, diagnostic and clinical activities and services reported to EPI/EPNET in yearly activity reports during 2006 through 2009 were compared between reporting centres, and possible time trends explored.ResultsThirty-five porphyria centres from 22 countries, five of which were non-European associate EPNET members, filed one or more activity reports to EPI/EPNET during the study period. Large variations between centres were observed in the analytical repertoire offered, numbers of analyses performed and type and number of staff engaged. The proportion of centres fulfilling the minimum criteria set by EPNET to be classified as a specialist porphyria centre increased from 80% to 94% during the study period.ConclusionsPorphyria services are unevenly distributed, and some areas are probably still lacking in specialized porphyria services altogether. However, improvements in the quality of diagnostic services provided by porphyria centres participating in EPI/EPNET were observed during 2006 through 2009.