Abstract
ObjectiveMitochondrial disease is a disorder of energy metabolism that affects 1 in 4300 adults in the UK. Pregnancy is associated with physiological demands that have implications for energy metabolism. We were interested to know how pregnancy was affected in women with mitochondrial disease, particularly those with the most common pathogenic mutation m.3243A>G.DesignRetrospective case‐comparison study.Population/SettingSixty‐seven women with genetically confirmed mitochondrial disease from the UK Mitochondrial Diseases Cohort and 69 unaffected women participated.MethodsParticipants answered questionnaires regarding each of their pregnancies. Patients were divided into two groups according to genetic mutation, with those harbouring m.3243A>G comprising a single group.Main outcome measuresPregnancy‐related complications, mode of delivery, gestational age and birthweight of newborns.ResultsOf 139 live births in the comparison group, 62 were in the m.3243A>G group and 87 were in the ‘all other mutations’ group. Pregnancies of women with the m.3243A>G mutation had significantly more gestational diabetes (odds ratio [OR] = 8.2, 95% CI 1.3–50.1), breathing difficulties (OR = 7.8, 95% CI 1.0–59.1) and hypertension (OR = 8.2, 95% CI 3.1–21.5) than the comparison group. Only half of the pregnancies in the m.3243A>G group had normal vaginal delivery, with emergency caesarean section accounting for 24.2% of deliveries. Babies were born significantly earlier to mothers harbouring m.3243A>G with 53.3% of them preterm (<37 weeks). These babies were also more likely to require resuscitation and admission.ConclusionWomen who carried the m.3243A>G mutation appeared to be at higher risk of complications during pregnancies, caesarean section and preterm delivery than the unaffected women or those with other forms of mitochondrial disease.Tweetable abstractPregnant women with mitochondrial disease – m.3243A>G mutation – are at greatly increased risk of complications and preterm delivery.
Highlights
IntroductionMitochondrial diseaseMitochondrial disease resulting from nuclear and mitochondrial DNA genetic mutations collectively affects 1 in 4300 adults in the UK.[1,2] The most common pathogenic point mutation of the mitochondrial genome is the m.3243A>G in the MTTL1 gene, with a carrier rate of 1 in 400 individuals.[3,4,5] This maternally inherited mutation is implicated in several clinical syndromes such as mitochondrial encephalopathy, lactic acidosis and strokelike episodes, maternally inherited deafness and diabetes, and progressive external ophthalmoplegia.[6,7] Affected patients may exhibit non-syndromic features such as seizures, myopathy, ptosis, migraine, ataxia, gut dysmotility or cognitive decline.[7]
BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists
One of the women with m.3243A>G was diagnosed at the birth of their first child and none of the women with m.3243A>G considered themselves to have any mitochondrial disease manifestations at the time of their pregnancies
Summary
Mitochondrial diseaseMitochondrial disease resulting from nuclear and mitochondrial DNA genetic mutations collectively affects 1 in 4300 adults in the UK.[1,2] The most common pathogenic point mutation of the mitochondrial genome is the m.3243A>G in the MTTL1 gene, with a carrier rate of 1 in 400 individuals.[3,4,5] This maternally inherited mutation is implicated in several clinical syndromes such as mitochondrial encephalopathy, lactic acidosis and strokelike episodes, maternally inherited deafness and diabetes, and progressive external ophthalmoplegia.[6,7] Affected patients may exhibit non-syndromic features such as seizures, myopathy, ptosis, migraine, ataxia, gut dysmotility or cognitive decline.[7]. Mitochondrial disease typically affects organs with high energy requirements such as the brain, skeletal muscle, heart and liver.[2] The normal physiological adaptations of pregnancy are likely to have bio-energetic consequences that increase the need for mitochondrial ATP production. These additional demands on ATP supply during pregnancy in the context of mitochondrial insufficiency may be an important mechanism in maternal and fetal complications. In the UK, there has been no large-scale study into the outcomes of pregnant women with mitochondrial disease. Knowledge gained from this study may provide insight into understanding the role of mitochondrial genetic defects in adverse pregnancy outcomes
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