Edwin Amalraj Raja

OBJECTIVES: To determine whether maternal obesity during pregnancy is associated with increased mortality from cardiovascular events in adult offspring. DESIGN: Record linkage cohort analysis. SETTING: Birth records from the Aberdeen Maternity and Neonatal databank linked to the General Register of Deaths, Scotland, and the Scottish Morbidity Record systems. POPULATION: 37 709 people with birth records from 1950 to present day. MAIN OUTCOME MEASURES: Death and hospital admissions for cardiovascular events up to 1 January 2012 in offspring aged 34-61. Maternal body mass index (BMI) was calculated from height and weight measured at the first antenatal visit. The effect of maternal obesity on outcomes in offspring was tested with time to event analysis with Cox proportional hazard regression to compare outcomes in offspring of mothers in underweight, overweight, or obese categories of BMI compared with offspring of women with normal BMI. RESULTS: All cause mortality was increased in offspring of obese mothers (BMI >30) compared with mothers with normal BMI after adjustment for maternal age at delivery, socioeconomic status, sex of offspring, current age, birth weight, gestation at delivery, and gestation at measurement of BMI (hazard ratio 1.35, 95% confidence interval 1.17 to 1.55). In adjusted models, offspring of obese mothers also had an increased risk of hospital admission for a cardiovascular event (1.29, 1.06 to 1.57) compared with offspring of mothers with normal BMI. The offspring of overweight mothers also had a higher risk of adverse outcomes. CONCLUSIONS: Maternal obesity is associated with an increased risk of premature death in adult offspring. As one in five women in the United Kingdom is obese at antenatal booking, strategies to optimise weight before pregnancy are urgently required.

BACKGROUND: Initial observational studies and a systematic review published 5 years ago have suggested that obstetric and perinatal outcomes are better in offspring conceived following frozen rather than fresh embryo transfers, with reduced risks of preterm birth, small for gestational age, low birth weight and pre-eclampsia. More recent primary studies are beginning to challenge some of these findings. We therefore conducted an updated systematic review and cumulative meta-analysis to examine if these results have remained consistent over time. OBJECTIVE AND RATIONALE: The aim of this study was to perform a systematic review and cumulative meta-analysis (trend with time) of obstetric and perinatal complications in singleton pregnancies following the transfer of frozen thawed and fresh embryos generated through in-vitro fertilisation. SEARCH METHODS: Data Sources from Medline, EMBASE, Cochrane Central Register of Clinical Trials DARE and CINAHL (1984-2016) were searched using appropriate key words. Observational and randomised studies comparing obstetric and perinatal outcomes in singleton pregnancies conceived through IVF using either fresh or frozen thawed embryos. Two independent reviewers extracted data in 2 × 2 tables and assessed the methodological quality of the relevant studies using CASP scoring. Both aggregated as well as cumulative meta-analysis was done using STATA. OUTCOMES: Twenty-six studies met the inclusion criteria. Singleton babies conceived from frozen thawed embryos were at lower relative risk (RR) of preterm delivery (0.90; 95% CI 0.84-0.97) low birth weight (0.72; 95% CI 0.67-0.77) and small for gestational age (0.61; 95% CI 0.56-0.67) compared to those conceived from fresh embryo transfers, but faced an increased risk (RR) of hypertensive disorders of pregnancy (1.29; 95% CI 1.07-1.56) large for gestational age (1.54; 95% CI 1.48-1.61) and high birth weight (1.85; 95% CI 1.46-2.33). There was no difference in the risk of congenital anomalies and perinatal mortality between the two groups. The direction and magnitude of effect for these outcomes have remained virtually unchanged over time while the degree of precision has improved with the addition of data from newer studies. WIDER IMPLICATIONS: The results of this cumulative meta-analysis confirm that the decreased risks of small for gestational age, low birth weight and preterm delivery and increased risks of large for gestational age and high birth weight associated with pregnancies conceived from frozen embryos have been consistent in terms of direction and magnitude of effect over several years, with increasing precision around the point estimates. Replication in a number of different populations has provided external validity for the results, for outcomes of birth weight and preterm delivery. Meanwhile, caution should be exercised about embarking on a policy of electively freezing all embryos in IVF as there are increased risks for large for gestational age babies and hypertensive disorders of pregnancy. Therefore, elective freezing should ideally be undertaken in specific cases such as ovarian hyperstimulation syndrome, fertility preservation or in the context of randomised trials.

One in 5 pregnant women is obese but the impact on later health is unknown. We aimed to determine whether maternal obesity during pregnancy associates with increased premature mortality and later life major cardiovascular events. Maternity records of women who gave birth to their first child between 1950 and 1976 (n=18 873) from the Aberdeen Maternity and Neonatal databank were linked to the National Register of Deaths, Scotland and Scottish Morbidity Record. The effect of maternal obesity at first antenatal visit on death and hospital admissions for cardiovascular events was tested using time-to-event analysis with Cox proportional hazard regression to compare outcomes of mothers in underweight, overweight, or obese body mass index (BMI) categories compared with normal BMI. Median follow-up was at 73 years. All-cause mortality was increased in women who were obese during pregnancy (BMI>30 kg/m(2)) versus normal BMI after adjustment for socioeconomic status, smoking, gestation at BMI measurement, preeclampsia, and low birth weight (hazard ratio, 1.35; 95% confidence interval, 1.02-1.77). In adjusted models, overweight and obese mothers had increased risk of hospital admission for a cardiovascular event (1.16; 1.06-1.27 and 1.26; 1.01-1.57) compared with normal BMI mothers. Adjustment for parity largely unchanged the hazard ratios (mortality: 1.43, 1.09-1.88; cardiovascular events overweight: 1.17, 1.07-1.29; and obese: 1.30, 1.04-1.62). In conclusion, maternal obesity is associated with increased risk of premature death and cardiovascular disease. Pregnancy and early postpartum could represent an opportunity for interventions to identify obesity and reduce its adverse consequences.

OBJECTIVE: To assess inherited predisposition to spontaneous preterm delivery. METHODS: In this retrospective cohort study, intergenerational data on deliveries in mother-daughter pairs were analyzed from the Aberdeen Maternity Neonatal Databank using multilevel logistic regression. The study included an exposed cohort of all women born spontaneously preterm or whose mothers had experienced at least one spontaneous preterm delivery (at 24-37 weeks of gestation). The unexposed cohort included women who were born at term (after 37 weeks of gestation) or those whose mothers had never experienced any spontaneous preterm deliveries (24-37 weeks of gestation). The primary outcome was spontaneous preterm delivery in the daughters' pregnancies. Results are shown as adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We identified 22,343 pregnancies occurring in 13,845 daughters born to 11,576 mothers. Women who were born spontaneously preterm had significantly higher odds of delivering preterm babies (OR 1.49, 95% CI 1.12-1.99). A stronger association was seen when the analysis was restricted to nulliparous women who had been born spontaneously preterm (OR 1.60, 95% CI 1.16-2.21). Other predictors of a woman having a spontaneous preterm delivery were age at delivery younger than 20 years (OR 1.67, 95% CI 1.43-1.94), lower socioeconomic status (OR 1.22, 95% CI 1.04-1.44), smoking more than 10 cigarettes per day (OR 1.47, 95% CI 1.27-1.71), body mass index 19 kg/m or less (OR 1.48, 95% CI 1.24-1.77), previous preterm delivery (OR 2.51, 95% CI 1.71-3.66). The risk of a woman delivering spontaneously preterm was increased even if her mother had a history of spontaneous preterm delivery in any other pregnancy (OR 1.35, 95% CI 1.12-1.63). The absolute risk of spontaneously delivering preterm in women who were born preterm was 9% as opposed to 6.2% in those who were born full-term. This gives an increase in risk of spontaneous preterm birth of 2.8% in women who were born spontaneously preterm. CONCLUSION: Women born spontaneously preterm or with siblings delivered in a similar manner have an increased risk of spontaneous preterm delivery in their own pregnancies. LEVEL OF EVIDENCE: II.