Birth Weights in Sickle Cell Disease Pregnancies: A Cohort Study.

Pregnancy in women with Sickle Cell Disease (SCD) has been linked with an increased incidence of adverse foetal outcomes when compared to women without haemoglobinopathies (HbAA). There's a paucity of data into foetal outcomes for infants born to women with SCD. Customised growth charts have been demonstrated to be better than population-based growth charts at identifying unhealthy small babies. We analysed the mean birth weight and customised birth weight centiles of infants born to mothers with SCD versus mothers with HbAA genotype, to quantify the risk of having a smaller baby. Birth weight and birth weight centiles were analysed for 88 women with SCD (50 HbSS; 38 HbSC) and 176 controls (HbAA). Statistically significant differences were seen in the mean birth weight (P value = 0.004) and the mean birth weight centiles (P value = 0.016). We conclude that SCD is a risk factor for having a smaller baby

A Systematic Review and Meta-Analysis of Non-Invasive Prenatal Diagnosis (NIPD) of Sickle Cell Disease (SCD)

Introduction: Sickle cell disease (SCD) is a genetically inherited, recessive mutation of the haemoglobin ?S-gene. Each year, over 300,000 babies are born with SCD, which will have a significant impact on their quality of life and average life expectancy. Currently, for SCD to be tested prenatally, foetal DNA is extracted by amniocentesis, chorionic villus sampling or cordocentesis, and then analysed by polymerase chain reaction (PCR), for instance. These procedures increase the risk of foetal miscarriage by less than 0.5%. SCD may, however, be tested non-invasively using cell-free foetal DNA (cffDNA), which is extracted from maternal blood plasma. In this study, the current accuracy of using cffDNA testing for non-invasive prenatal diagnosis (NIPD) of SCD will be shown. Methods: Using databases such as PubMed, Web of Science and Scopus, this study systematically reviewed existing studies pertaining to the use of cffDNA maternal blood samples for non-invasive prenatal testing (NIPT) or diagnosis (NIPD) for SCD in patients who were at risk of having a baby with SCD. The data collected from the systematic review of the studies was statistically analysed in the form of a meta-analysis, describing the proportion of correct diagnosis results for this method of prenatal testing. Results: Of over 3,600 papers identified from the database searches, only five studies contained data pertaining to the use of cffDNA for prenatal testing of SCD and conformed to the inclusion criteria set out by this study. Collectively, these data showed an average of 81.30% accuracy of diagnosis when using cffDNA to test for SCD, with 18.70% of foetuses incorrectly diagnosed. These data were compiled as a Forest Plot meta-analysis. Conclusion: CffDNA for non-invasive prenatal SCD diagnosis appears to have the potential to be an accurate technique for the testing of this genetic disease, despite not currently indicating a proportion of correct diagnosis results which would encourage the technique for clinical implementation. Whilst there are currently very limited data on the use of this technique for the specific testing of SCD, there is great opportunity for further research into the standardisation and clinical application of this procedure

Risk of Adverse Obstetric and Neonatal Outcomes by Maternal Age: Quantifying Individual and Population Level Risk Using Routine UK Maternity Data.

OBJECTIVE: The objective of this study was to investigate whether moderately increased maternal age is associated with obstetric and neonatal outcome in a contemporary population, and to consider the possible role of co-morbidities in explaining any increased risk. STUDY DESIGN: Secondary analysis of routinely collected data from a large maternity unit in London, UK. Data were available on 51,225 singleton deliveries (≥22 weeks) occurring to women aged ≥20 between 2004 and 2012. Modified Poisson regression was used to estimate risk ratios for the association between maternal age and obstetric and neonatal outcome (delivery type, postpartum haemorrhage, stillbirth, low birthweight, preterm birth, small for gestational age, neonatal unit admission), using the reference group 20-24 years. Population attributable fractions were calculated to quantify the population impact. RESULTS: We found an association between increasing maternal age and major postpartum haemorrhage (≥1000ml blood loss) (RR 1.36 95% CI 1.18-1.57 for age 25-29 rising to 2.41 95% CI 2.02-2.88 for age ≥40). Similar trends were observed for caesarean delivery, most notably for elective caesareans (RR 1.64 95% CI 1.36-1.96 for age 25-29 rising to 4.94 95% CI 4.09-5.96 for age ≥40). There was evidence that parity modified this association, with a higher prevalence of elective caesarean delivery in older nulliparous women. Women aged ≥35 were at increased risk of low birthweight and preterm birth. We found no evidence that the risk of stillbirth, small for gestational age, or neonatal unit admission differed by maternal age. CONCLUSIONS: Our results suggest a gradual increase in the risk of caesarean delivery and postpartum haemorrhage from age 25, persisting after taking into account maternal BMI, hypertension and diabetes. The risk of low birthweight and preterm birth was elevated in women over 35. Further research is needed to understand the reasons behind the high prevalence of elective caesarean delivery in nulliparous older mothers

Lifestyle interventions for overweight and obese pregnant women to improve pregnancy outcome: systematic review and meta-analysis

BACKGROUND: Overweight and obesity pose a big challenge to pregnancy as they are associated with adverse maternal and perinatal outcome. Evidence of lifestyle intervention resulting in improved pregnancy outcome is conflicting. Hence the objective of this study is to determine the efficacy of antenatal dietary, activity, behaviour or lifestyle interventions in overweight and obese pregnant women to improve maternal and perinatal outcomes. METHODS: A systematic review and meta-analyses of randomised and non-randomised clinical trials following prior registration (CRD420111122 http://www.crd.york.ac.uk/PROSPERO) and PRISMA guidelines was employed. A search of the Cochrane Library, EMBASE, MEDLINE, CINAHL, Maternity and Infant care and eight other databases for studies published prior to January 2012 was undertaken. Electronic literature searches, study selection, methodology and quality appraisal were performed independently by two authors. Methodological quality of the studies was assessed according to Cochrane risk of bias tool. All appropriate randomised and non-randomised clinical trials were included while exclusions consisted of interventions in pregnant women who were not overweight or obese, had pre-existing diabetes or polycystic ovarian syndrome, and systematic reviews. Maternal outcome measures, including maternal gestational weight gain, gestational diabetes and Caesarean section, were documented. Fetal outcomes, including large for gestational age and macrosomia (birth weight > 4 kg), were also documented. RESULTS: Thirteen randomised and six non-randomised clinical trials were identified and included in the meta-analysis. The evidence suggests antenatal dietary and lifestyle intervention in obese pregnant women reduces maternal pregnancy weight gain (10 randomised clinical trials; n = 1228; -2.21 kg (95% confidence interval -2.86 kg to -1.59 kg)) and a trend towards a reduction in the prevalence of gestational diabetes (six randomised clinical trials; n = 1,011; odds ratio 0.80 (95% confidence interval 0.58 to 1.10)). There were no clear differences reported for other outcomes such as Caesarean delivery, large for gestational age, birth weight or macrosomia. All available studies were assessed to be of low to medium quality. CONCLUSION: Antenatal lifestyle intervention is associated with restricted gestational weight gain and a trend towards a reduced prevalence of gestational diabetes in the overweight and obese population. These findings need to be interpreted with caution as the available studies were of poor to medium quality

Maternal BMI and diabetes in pregnancy: Investigating variations between ethnic groups using routine maternity data from London, UK.

OBJECTIVE: To investigate the ethnicity-specific association between body mass index (BMI) and diabetes in pregnancy, with a focus on the appropriateness of using BMI cut-offs to identify pregnant women at risk of diabetes. STUDY DESIGN: Analysis of routinely-collected data from a maternity unit in London, UK. Data were available on 53 264 women delivering between 2004 and 2012. Logistic regression was used to explore the association between diabetes in pregnancy and BMI among women of different ethnicities, and adjusted probability estimates were used to derive risk equivalent cut-offs. ROC curve analysis was used to assess the performance of BMI as a predictor of diabetes in pregnancy. RESULTS: The prevalence of diabetes in pregnancy was 2.3% overall; highest in South and East Asian women (4.6% and 3.7%). In adjusted analysis, BMI category was strongly associated with diabetes in all ethnic groups. Modelled as a continuous variable with a quadratic term, BMI was an acceptable predictor of diabetes according to ROC curve analysis. Applying a BMI cut-off of 30 kg/m2 would identify just over half of Black women with diabetes in pregnancy, a third of White (32%) and South Asian (35%) women, but only 13% of East Asian women. The 'risk equivalent' (comparable to 30 kg/m2 in White women) threshold for South Asian and East Asian women was approximately 21 kg/m2, and 27.5 kg/m2 for Black women. CONCLUSIONS: This study suggests that current BMI thresholds are likely to be ineffective for diabetes screening in South and East Asian women, as many cases of diabetes will occur at low BMI levels. Our results suggest that East Asian women appear to face a similarly high risk of diabetes to South Asian women. Current UK guidelines recommend diabetes screening should be offered to all pregnant South Asian women; extending this recommendation to include women of East Asian ethnicity may be appropriate

Ethnic variation in stillbirth risk and the role of maternal obesity: analysis of routine data from a London maternity unit.

BACKGROUND: Approximately 5 in 1,000 deliveries in England and Wales result in stillbirth, with little improvement in figures over the last few decades. The aim of this study was to investigate the association between clinical and socio-demographic factors and stillbirth, with a particular focus on ethnicity and obesity. METHODS: Analysis of routine maternity data on 53,293 singleton births occurring in a large London teaching hospital between 2004 and 2012. Logistic regression was used to investigate risk factors for stillbirth and to explore potential effect modification. RESULTS: 53,293 deliveries occurred during the time period, of which 329 resulted in a stillbirth (6.2 per 1,000 births). Compared to White women, non-White ethnicity was associated with a doubling of the odds of stillbirth (aOR for Black women 2.15, 95% CI 1.56-2.97; aOR for South Asian women 2.33, 95% CI 1.42-3.83). Obese women had a trend towards higher odds of stillbirth compared to women of recommended BMI (aOR 1.38, 95% CI 0.98-1.96), though this was not significant (p 0.07). Both higher parity (≥2 compared to para 1) and hypertension were associated with a higher odds of stillbirth (parity ≥2 aOR 1.65, 95% CI 1.13-2.39; hypertension aOR 1.84, 95% CI 1.22-2.78) but there was no evidence that area deprivation or maternal age were independently associated with stillbirth in this population. There was some evidence of effect modification between ethnicity and obesity (p value for interaction 0.06), with obesity a particularly strong risk factor for stillbirth in South Asian women (aOR 4.64, 95% CI 1.84-11.70). CONCLUSIONS: There was a high prevalence of stillbirth in this multi-ethnic urban population. The increased risk of stillbirth observed in non-White women remains after adjusting for other factors. Our finding of possible effect modification between ethnicity and obesity suggests that further research should be conducted in order to improve understanding of the interplay between ethnicity, obesity and stillbirth

Interpregnancy weight change and adverse pregnancy outcomes: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the effect of interpregnancy body mass index (BMI) change on pregnancy outcomes, including large-for-gestational-age babies (LGA), small-for-gestational-age babies (SGA), macrosomia, gestational diabetes mellitus (GDM) and caesarean section (CS). DESIGN: Systematic review and meta-analysis of observational cohort studies. DATA SOURCES: Literature searches were performed across Cochrane, MEDLINE, EMBASE, CINAHL, Global Health and MIDIRS databases. STUDY SELECTION: Observational cohort studies with participants parity from 0 to 1. MAIN OUTCOME MEASURES: Adjusted ORs (aORs) with 95% CIs were used to evaluate the association between interpregnancy BMI change on five outcomes. RESULTS: 925 065 women with singleton births from parity 0 to 1 were included in the meta-analysis of 11 studies selected from 924 identified studies. A substantial increase in interpregnancy BMI (>3 BMI units) was associated with an increased risk of LGA (aOR 1.85, 95% CI 1.71 to 2.00, p<0.001), GDM (aOR 2.28, 95% CI 1.97 to 2.63, p<0.001), macrosomia (aOR 1.54, 95% CI 0.939 to 2.505) and CS (aOR 1.72, 95% CI 1.32 to 2.24, p<0.001) compared with the reference category, and a decreased risk of SGA (aOR 0.83, 95% CI 0.70 to 0.99, p=0.044). An interpregnancy BMI decrease was associated with a decreased risk of LGA births (aOR 0.70, 95% CI 0.55 to 0.90, p<0.001) and GDM (aOR 0.80, 95% CI 0.62 to 1.03), and an increased risk of SGA (aOR 1.31, 95% CI 1.06 to 1.63, p=0.014). Women with a normal BMI (<25kg/m2) at first pregnancy who have a substantial increase in BMI between pregnancies had a higher risk of LGA (aOR 2.10, 95% CI 1.93 to 2.29) and GDM (aOR 3.10, 95% CI 2.74 to 3.50) when compared with a reference than women with a BMI ≥25 kg/m2 at first pregnancy. CONCLUSIONS: Gaining weight between pregnancies increases risk of developing GDM, CS and LGA, and reduces risk of SGA in the subsequent pregnancy. Losing weight between pregnancies reduces risk of GDM and LGA and increases risk of SGA. Weight stability between first and second pregnancy is advised in order to reduce risk of adverse outcomes. TRIAL REGISTRATION NUMBER: CRD42016041299

Pulmonary complications for women with sickle cell disease in pregnancy: systematic review and meta-analysis.

BACKGROUND: Sickle cell disease (SCD) is a multisystem disease characterised by vaso-occlusive crisis, chronic anaemia and a shorter lifespan. More patients with SCD are living till reproductive age and contemplating pregnancy. Pulmonary complications in pregnancy are significant causes of maternal morbidity and mortality but yet this has not been systematically quantified. A systematic review and meta-analysis were conducted to quantify the association between SCD and pulmonary complications in pregnancy. METHODS: MEDLINE, EMBASE, Web of Science, Cochrane and Maternity and Infant Care databases were searched for publications between January 1998 and April 2019. Observational studies involving at least 30 participants were included. Random-effects models were used for statistical meta-analysis. FINDINGS: Twenty-two studies were included in the systematic review and 18 in the quantitative analysis. The meta-analysis included 3964 pregnancies with SCD and 336 559 controls. Compared with women without SCD, pregnancies complicated by SCD were at increased risk of pulmonary thromboembolism (relative risk (RR) 7.74; 95% CI 4.65 to 12.89). The estimated prevalence of acute chest syndrome and pneumonia was 6.46% (95% CI 4.66% to 8.25%), with no significant difference between the HbSS and HbSC genotypes (RR 1.42; 95% CI 0.90 to 2.23). INTERPRETATION: This meta-analysis highlighted a strong association between SCD and maternal pulmonary complications. Understanding the risks of and the factors associated with pulmonary complications would aid preconceptual counselling and optimal management of the condition in pregnancy, thereby reducing associated maternal morbidity and mortality. PROSPERO REGISTRATION NUMBER: CRD42019124708

Does first-trimester serum pregnancy-associated plasma protein A differ in pregnant women with sickle cell disease?

OBJECTIVE: To assess whether levels of first-trimester pregnancy-associated plasma protein A (PAPP-A) differ between women with and without sickle cell disease (SCD). METHODS: Retrospective study of 101 singleton pregnancies in women with SCD (including 55 with genotype HbSS, 37 with genotype HbSC, and nine with other genotypes). Measured levels of PAPP-A were converted to multiple of the median (MoM) values corrected for gestational age and maternal characteristics. Median PAPP-A MoM in the SCD group was compared with that of 1010 controls. RESULTS: In the SCD group median, PAPP-A MoM was lower than in the non-SCD group (0.72, interquartile range [IQR] = 0.54-1.14 versus 1.09, IQR = 0.74-1.49; P < .001). Within the SCD group median PAPP-A MoM was lower for those with genotype HbSS than HbSC (0.62, IQR = 0.44-1.14 versus 0.94, IQR = 0.72-1.25; .006). In 7.3% (4/55) of the HbSS group, there was stillbirth, and in these cases, PAPP-A was less than or equal to 0.5 MoM; in the control group, the incidence of stillbirth was lower (1%; P < .001). In HbSS disease, the incidence of small for gestational age (SGA) neonates was increased. CONCLUSION: Pregnancies with HbSS have lower PAPP-A MoM values and higher incidence of stillbirth and birth of SGA neonates than in non-SCD controls

Cumulative outcome of pre-implantation genetic diagnosis for sickle cell disease: a 5-year review.

To review the cumulative outcome of pre-implantation genetic diagnosis (PGD) cycles performed for prevention of sickle cell disease (SCD). Couples referred for PGD for SCD between April 2012 and October 2017 were included. Ovarian stimulation was performed using a short gonadotrophin-releasing hormone (GnRH) antagonist protocol and follicle-stimulating hormone injections. The GnRH agonist was used to trigger oocyte maturation. Oocytes were fertilised using intracytoplasmic sperm injection. Trophectoderm biopsy was performed on day 5 or 6 followed by vitrification. Genetic testing was done using pre-implantation genetic haplotyping. A total of 60 couples started 70 fresh PGD cycles (mean 1·2 cycles/couple) and underwent a total of 74 frozen-embryo-transfer (FET) cycles (mean 1·3 FET/couple). The mean (SD) female age was 33 (4·4) years and the mean (SD) anti-müllerian hormone level was 22·9 (2·8) pmol/l. The cumulative live-birth rate was 54%/PGD cycle started and 63%/couple embarking on PGD. The rate of multiple births was 8%. The cumulative outcome of PGD treatment for prevention of SCD transmission is high and PGD treatment should be offered to all at-risk couples