A case-comparison study of pregnant women with mitochondrial disease - what to expect?

Abstract

Objective: Mitochondrial 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.

Design: Retrospective case-comparison study.

Population/setting: Sixty-seven women with genetically confirmed mitochondrial disease from the UK Mitochondrial Diseases Cohort and 69 unaffected women participated.

Methods: Participants 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 measures: Pregnancy-related complications, mode of delivery, gestational age and birthweight of newborns.

Results: Of 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.

Conclusion: Women 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 abstract: Pregnant women with mitochondrial disease - m.3243A>G mutation - are at greatly increased risk of complications and preterm delivery.

Keywords: MTTL1; Birthweight; breathing difficulties; gestation; gestational diabetes; hypertension; m.3243A>G; mitochondria; mitochondrial disease; pregnancy; pregnant women with mitochondrial disease.

Figure 1

Participation flow chart. ^aTwo women excluded because of twin pregnancies. ^bPL, pregnancy loss or miscarriage; ^cTOP, termination of pregnancy. ^dIncomplete for analysis – no reliable pregnancy details disclosed on stillbirths.

Figure 2

Percentage of pregnancies in which women had experienced bleeding, anaemia, gestational diabetes, breathing problems and high blood pressure. Women with m.3243A>G experienced significantly more (gestational) diabetes and high blood pressure during pregnancies than women in comparison groups *P < 0.05; **P ≤ 0.001. (Generalised linear models, accounting for multiple births).

Figure 3

Modes of delivery of three study groups. Only half of the deliveries in the m.3243A>G group were normal vaginal deliveries; significantly fewer than in the comparison group. In the remaining half of the m.3243A>G deliveries, emergency caesarean section was the most common mode of delivery.

Figure 4

Newborn outcomes. (A) Gestation of babies (in days); (B) Birthweight of babies (in grams). Babies born to mothers with m.3243A>G had significantly lower gestational age and birthweight than both other mutations and comparison groups. (C) Birthweight centile corrected for gestation. No difference between all three groups. (D) Babies born to mothers with m.3243A>G had significantly more resuscitations at birth and admissions to SCBU. *P < 0.05; **P ≤ 0.001 (Generalised linear models, accounting for multiple births).