• The effects of maternal body mass index on pregnancy outcome.

      Khashan, A S; Kenny, L C; The Anu Research Centre, Department of Obstetrics and Gynaecology, Cork, University Maternity Hospital, University College Cork, Wilton, Cork, Ireland., a.khashan@ucc.ie (2012-01-31)
      The increasing prevalence of obesity is presenting a critical challenge to healthcare services. We examined the effect of Body Mass Index in early pregnancy on adverse pregnancy outcome. We performed a population register-based cohort study using data from the North Western Perinatal survey (N = 99,403 babies born during 2004-2006), based at The University of Manchester, UK. The main outcome measures were Caesarean section delivery, preterm birth, neonatal death, stillbirth, Macrosomia, small for gestational age and large for gestational age. The risk of preterm birth was reduced by almost 10% in overweight (RR = 0.89, [95% CI: 0.83, 0.95]) and obese women (RR = 0.90, [95% CI: 0.84, 0.97]) and was increased in underweight women (RR = 1.33, [95% CI: 1.16, 1.53]). Overweight (RR = 1.17, [95% CI: 1.09, 1.25]), obese (RR = 1.35, [95% CI: 1.25, 1.45]) and morbidly obese (RR = 1.24, [95% CI: 1.02, 1.52]) women had an elevated risk of post-term birth compared to normal women. The risk of fetal macrosomia and operative delivery increased with BMI such that morbidly obese women were at greatest risk of both (RR of macrosomia = 4.78 [95% CI: 3.86, 5.92] and RR of Caesarean section = 1.66 [95% CI: 1.61, 1.71] and a RR of emergency Caesarean section = 1.59 [95% CI: 1.45, 1.75]). Excessive leanness and obesity are associated with different adverse pregnancy outcomes with major maternal and fetal complications. Overweight and obese women have a higher risk of macrosomia and Caesarean delivery and lower risk of preterm delivery. The mechanism underlying this association is unclear and is worthy of further investigation.
    • The impact of maternal celiac disease on birthweight and preterm birth: a Danish population-based cohort study.

      Khashan, A S; Henriksen, T B; Mortensen, P B; McNamee, R; McCarthy, F P; Pedersen, M G; Kenny, L C; Anu Research Centre, Department of Obstetrics and Gynecology, University College , Cork, Cork University Maternity Hospital, Cork, Ireland. a.khashan@ucc.ie (2012-01-31)
      BACKGROUND: Adverse pregnancy outcomes have been associated with maternal celiac disease (CD). In this study, we investigate the effect of treated and untreated maternal CD on infant birthweight and preterm birth. METHODS: A population-based cohort study consisted of all singleton live births in Denmark between 1 January 1979 and 31 December 2004 was used. A total of 1,504,342 babies were born to 836,241 mothers during the study period. Of those, 1105 babies were born to women with diagnosed CD and 346 were born to women with undiagnosed CD. Women with diagnosed CD were considered as treated with a gluten free diet while women with undiagnosed CD were considered as untreated. The outcome measures were: birthweight, small for gestational age (SGA: birthweight <10th centile), very small for gestational age (VSGA: birthweight <5th centile) and preterm birth. We compared these measures in treated and untreated women with those of a reference group (no history of CD). RESULTS: Women with untreated CD delivered smaller babies [difference = -98 g (95% CI: -130, -67)], with a higher risk of SGA infants [OR = 1.31 (95% CI: 1.06, 1.63)], VSGA infants [OR = 1.54 (95% CI: 1.17, 2.03)] and preterm birth [OR = 1.33 (95% CI: 1.02, 1.72)] compared with women without CD. Women with treated CD had no increased risk of reduced mean birthweight, risk of delivering SGA and VSGA infants or preterm birth compared with women without CD. CONCLUSION: Untreated maternal CD increases the risk of reduced birthweight, the risk of delivering SGA and VSGA infants and preterm birth. Diagnosis and presumed treatment of maternal CD with a gluten-free diet appeared to result in a birthweight and preterm birth rate similar to those in women without CD.
    • Risk of affective disorders following prenatal exposure to severe life events: a Danish population-based cohort study.

      Khashan, Ali S; McNamee, Roseanne; Henriksen, Tine B; Pedersen, Marianne G; Kenny, Louise C; Abel, Kathryn M; Mortensen, Preben B; Anu Research Centre, Department of Obstetrics and Gynecology, University College , Cork, Cork University Maternity Hospital, Cork, Ireland. a.khashan@ucc.ie (2012-01-31)
      OBJECTIVE: To examine the effect of prenatal exposure to severe life events on risk of affective disorders in the offspring. METHODS: In a cohort of 1.1 million Danish births from May 1978 until December 1997, mothers were considered exposed if one (or more) of their close relatives died or was diagnosed with serious illness up to 6 months before conception or during pregnancy. Offspring were followed up from their 10th birthday until their death, migration, onset of affective disorder or 31 December 2007; hospital admissions were identified by linkage to the Central Psychiatric Register. Log-linear Poisson regression was used for data analysis. RESULTS: The risk of affective disorders was increased in male offspring whose mothers were exposed to severe life events during the second trimester (adjusted RR 1.55 [95% CI 1.05-2.28]). There was an increased risk of male offspring affective disorders in relation to maternal exposure to death of a relative in the second trimester (adjusted RR 1.74 [95% CI 1.06-2.84]) or serious illness in a relative before pregnancy (adjusted RR 1.44 [95% CI 1.02-2.05]). There was no evidence for an association between prenatal exposure to severe life events and risk of female offspring affective disorders. CONCLUSIONS: Our population-based study suggests that prenatal maternal exposure to severe life events may increase the risk of affective disorders in male offspring. These findings are consistent with studies of populations exposed to famine and earthquake disasters which indicate that prenatal environment may influence the neurodevelopment of the unborn child.
    • Robust early pregnancy prediction of later preeclampsia using metabolomic biomarkers.

      Kenny, Louise C; Broadhurst, David I; Dunn, Warwick; Brown, Marie; North, Robyn A; McCowan, Lesley; Roberts, Claire; Cooper, Garth J S; Kell, Douglas B; Baker, Philip N; et al. (2012-01-31)
      Preeclampsia is a pregnancy-specific syndrome that causes substantial maternal and fetal morbidity and mortality. The etiology is incompletely understood, and there is no clinically useful screening test. Current metabolomic technologies have allowed the establishment of metabolic signatures of preeclampsia in early pregnancy. Here, a 2-phase discovery/validation metabolic profiling study was performed. In the discovery phase, a nested case-control study was designed, using samples obtained at 15+/-1 weeks' gestation from 60 women who subsequently developed preeclampsia and 60 controls taking part in the prospective Screening for Pregnancy Endpoints cohort study. Controls were proportionally population matched for age, ethnicity, and body mass index at booking. Plasma samples were analyzed using ultra performance liquid chromatography-mass spectrometry. A multivariate predictive model combining 14 metabolites gave an odds ratio for developing preeclampsia of 36 (95% CI: 12 to 108), with an area under the receiver operator characteristic curve of 0.94. These findings were then validated using an independent case-control study on plasma obtained at 15+/-1 weeks from 39 women who subsequently developed preeclampsia and 40 similarly matched controls from a participating center in a different country. The same 14 metabolites produced an odds ratio of 23 (95% CI: 7 to 73) with an area under receiver operator characteristic curve of 0.92. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of preeclampsia offers insight into disease pathogenesis and offers the tantalizing promise of a robust presymptomatic screening test.
    • Secondary recurrent miscarriage is associated with previous male birth.

      Ooi, Poh Veh; Russell, Noirin; O'Donoghue, Keelin; Anu Research Centre, Department of Obstetrics and Gynaecology, University College, Cork, Cork University Maternity Hospital, Wilton, Cork, Ireland. (2012-01-31)
      Secondary recurrent miscarriage (RM) is defined as three or more consecutive pregnancy losses after delivery of a viable infant. Previous reports suggest that a firstborn male child is associated with less favourable subsequent reproductive potential, possibly due to maternal immunisation against male-specific minor histocompatibility antigens. In a retrospective cohort study of 85 cases of secondary RM we aimed to determine if secondary RM was associated with (i) gender of previous child, maternal age, or duration of miscarriage history, and (ii) increased risk of pregnancy complications. Fifty-three women (62.0%; 53/85) gave birth to a male child prior to RM compared to 32 (38.0%; 32/85) who gave birth to a female child (p=0.002). The majority (91.7%; 78/85) had uncomplicated, term deliveries and normal birth weight neonates, with one quarter of the women previously delivered by Caesarean section. All had routine RM investigations and 19.0% (16/85) had an abnormal result. Fifty-seven women conceived again and 33.3% (19/57) miscarried, but there was no significant difference in failure rates between those with a previous male or female child (13/32 vs. 6/25, p=0.2). When patients with abnormal results were excluded, or when women with only one previous child were considered, there was still no difference in these rates. A previous male birth may be associated with an increased risk of secondary RM but numbers preclude concluding whether this increases recurrence risk. The suggested association with previous male birth provides a basis for further investigations at a molecular level.
    • Secondary recurrent miscarriage is associated with previous male birth.

      Ooi, Poh Veh; Russell, Noirin; O'Donoghue, Keelin; Anu Research Centre, Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Wilton, Cork, Ireland. (2011-01)
      Secondary recurrent miscarriage (RM) is defined as three or more consecutive pregnancy losses after delivery of a viable infant. Previous reports suggest that a firstborn male child is associated with less favourable subsequent reproductive potential, possibly due to maternal immunisation against male-specific minor histocompatibility antigens. In a retrospective cohort study of 85 cases of secondary RM we aimed to determine if secondary RM was associated with (i) gender of previous child, maternal age, or duration of miscarriage history, and (ii) increased risk of pregnancy complications. Fifty-three women (62.0%; 53/85) gave birth to a male child prior to RM compared to 32 (38.0%; 32/85) who gave birth to a female child (p=0.002). The majority (91.7%; 78/85) had uncomplicated, term deliveries and normal birth weight neonates, with one quarter of the women previously delivered by Caesarean section. All had routine RM investigations and 19.0% (16/85) had an abnormal result. Fifty-seven women conceived again and 33.3% (19/57) miscarried, but there was no significant difference in failure rates between those with a previous male or female child (13/32 vs. 6/25, p=0.2). When patients with abnormal results were excluded, or when women with only one previous child were considered, there was still no difference in these rates. A previous male birth may be associated with an increased risk of secondary RM but numbers preclude concluding whether this increases recurrence risk. The suggested association with previous male birth provides a basis for further investigations at a molecular level.
    • Trial of labour after caesarean section and the risk of neonatal and infant death: a nationwide cohort study.

      O'Neill, Sinéad M; Agerbo, Esben; Khashan, Ali S; Kearney, Patricia M; Henriksen, Tine Brink; Greene, Richard A; Kenny, Louise C (BMC Pregnancy and Childbirth, 2017-02-27)
      Caesarean section (CS) rates are increasing worldwide and as a result repeat CS is common. The optimal mode of delivery in women with one previous CS is widely debated and the risks to the infant are understudied. The aim of the current study was to evaluate if women with a trial of labour after caesarean (TOLAC) had an increased odds of neonatal and infant death compared to women with an elective repeat CS (ERCS).