Louise Webster

Adverse maternal and perinatal outcomes in pregnant women with sickle cell disease: systematic review and meta-analysis.

A systematic review and meta-analysis of observational studies were conducted to quantify the association between sickle cell disease in pregnancy and adverse maternal and perinatal outcomes. Data sources (Medline, Embase, Maternity and Infant care, Cochrane, Web of Science, Popline) were searched for publications to June 2014. Eligibility criteria included observational studies reporting maternal and perinatal health outcomes in pregnant women with sickle cell disease against a comparative group of pregnant women without sickle cell disease. Twenty-one studies (including 26,349 women with sickle cell disease; 26,151,746 women without sickle cell disease) were eligible for inclusion. Pregnancies in women with HbSS genotype, compared with women without sickle cell disease, were at increased risk of maternal mortality (relative risk [RR], 5.98; 95% confidence interval [CI], 1.94-18.44), preeclampsia (RR, 2.43; 95% CI, 1.75-3.39), stillbirth (RR, 3.94; 95% CI, 2.60-5.96), preterm delivery (RR, 2.21; 95% CI, 1.47-3.31), and small for gestational age infants (RR, 3.72; 95% CI, 2.32-5.98). Meta-regression demonstrated that genotype (HbSS vs HbSC), low gross national income, and high study quality were associated with increased RRs. Despite advances in the management of sickle cell disease, obstetrics, and neonatal medicine, pregnancies complicated by the disease remain associated with increased risk of adverse maternal and perinatal outcomes.

Tacrolimus is an effective treatment for lupus nephritis in pregnancy

Lupus nephritis during pregnancy increases morbidity and mortality for mother and baby. Flares are difficult to treat as many therapeutic options are teratogenic or fetotoxic. Steroids alone may be unable to control disease activity and are associated with higher rates of preterm delivery, sepsis and gestational diabetes. Reports of using tacrolimus to treat lupus nephritis in pregnancy are limited. We describe the pregnancies of nine women in whom tacrolimus was successfully used to treat lupus nephritis flare (six patients) or maintain stable disease (three patients). Introduction or dose escalation of oral steroids was avoided in five of the patients who developed active disease and steroid dose was rapidly reduced in the sixth patient. All women with disease flare attained partial or complete remission after starting tacrolimus. None of the women on maintenance treatment developed active disease. We propose tacrolimus as an effective adjuvant or alternative therapy to steroids for treating lupus nephritis flare or maintaining stable disease during pregnancy.

Diagnostic accuracy of placental growth factor and ultrasound parameters to predict the small-for-gestational-age infant in women presenting with reduced symphysis-fundus height.

To assess the diagnostic accuracy of placental growth factor (PlGF) and ultrasound parameters to predict delivery of a small‐for‐gestational‐age (SGA) infant in women presenting with reduced symphysis–fundus height (SFH).

Impact of antihypertensive treatment on maternal and perinatal outcomes in pregnancy complicated by chronic hypertension: A systematic review and meta-analysis

Background Chronic hypertension complicates around 3% of all pregnancies. There is evidence that treating severe hypertension reduces maternal morbidity. This study aimed to systematically review randomized controlled trials of antihypertensive agents treating chronic hypertension in pregnancy to determine the effect of this intervention. Methods and Results Medline (via OVID), Embase (via OVID) and the Cochrane Trials Register were searched from their earliest entries until November 30, 2016. All randomized controlled trials evaluating antihypertensive treatments for chronic hypertension in pregnancy were included. Data were extracted and analyzed in Stata (version 14.1). Fifteen randomized controlled trials (1166 women) were identified for meta‐analysis. A clinically important reduction in the incidence of severe hypertension was seen with antihypertensive treatment versus no antihypertensive treatment/placebo (5 studies, 446 women; risk ratio 0.33, 95%CI 0.19‐0.56; I2 0.0%). There was no difference in the incidence of superimposed pre‐eclampsia (7 studies, 727 women; risk ratio 0.74, 95%CI 0.49‐1.11; I2 28.1%), stillbirth/neonatal death (4 studies, 667 women; risk ratio 0.37, 95%CI 0.11‐1.26; I2 0.0%), birth weight (7 studies, 802 women; weighted mean difference −60 g, 95%CI −200 to 80 g; I2 0.0%), or small for gestational age (4 studies, 369 women; risk ratio 1.01, 95%CI 0.53‐1.94; I2 0.0%) with antihypertensive treatment versus no treatment/placebo. Conclusions Antihypertensive treatment reduces the risk of severe hypertension in pregnant women with chronic hypertension. A considerable paucity of data exists to guide choice of antihypertensive agent. Adequately powered head‐to‐head randomized controlled trials of commonly used antihypertensive agents are required to inform prescribing.

Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: A Randomized Controlled Trial

Data from randomized controlled trials to guide antihypertensive agent choice for chronic hypertension in pregnancy are limited; this study aimed to compare labetalol and nifedipine, additionally assessing the impact of ethnicity on treatment efficacy. Pregnant women with chronic hypertension (12+0–27+6 weeks’ gestation) were enrolled at 4 UK centers (August 2014 to October 2015). Open-label first-line antihypertensive treatment was randomly assigned: labetalol- (200–1800 mg/d) or nifedipine-modified release (20–80 mg/d). Analysis included 112 women (98%) who completed the study (labetalol n=55, nifedipine n=57). Maximum blood pressure after randomization was 161/101 mm Hg with labetalol versus 163/105 mm Hg with nifedipine (mean difference systolic: 1.2 mm Hg [−4.9 to 7.2 mm Hg], diastolic: 3.3 mm Hg [−0.6 to 7.3 mm Hg]). Mean blood pressure was 134/84 mm Hg with labetalol and 134/85 mm Hg with nifedipine (mean difference systolic: 0.3 mm Hg [−2.8 to 3.4 mm Hg], and diastolic: −1.9 mm Hg [−4.1 to 0.3 mm Hg]). Nifedipine use was associated with a 7.4-mm Hg reduction (−14.4 to −0.4 mm Hg) in central aortic pressure, measured by pulse wave analysis. No difference in treatment effect was observed in black women (n=63), but a mean 4 mm Hg reduction (−6.6 to −0.8 mm Hg; P=0.015) in brachial diastolic blood pressure was observed with labetalol compared with nifedipine in non-black women (n=49). Labetalol and nifedipine control mean blood pressure to target in pregnant women with chronic hypertension. This study provides support for a larger definitive trial scrutinizing the benefits and side effects of first-line antihypertensive treatment. Clinical Trial Registration— URL: https://www.isrctn.com. Unique identifier: ISRCTN40973936.

Commentary on 'A multicentre randomised controlled trial comparing elective and selective caesarean section for the delivery of the preterm breech infant'.

The optimal mode of delivery of the preterm infant presenting in the breech position remains an unanswered question for obstetricians providing intrapartum care, and practice varies according to clinician and patient preference. In 1989 Penn et al. designed and began a multicentre randomised controlled trial comparing vaginal delivery with caesarean section for preterm breech infants. Unfortunately recruitment fell way short of targets, and the trial was called to a halt after 13 recruits in 27 months. The low incidence of the condition, lack of clinician equipoise and ethical issues of taking truly informed consent from laboring women are all to blame. Yet, the intrapartum period is a time when good quality trials are vital, and evidence is lacking. Are we any closer to facilitating research in this environment? The obstetric labour ward setting provides a unique and challenging environment in which rapid clinical judgement and decision-making skills must be deployed to ensure a safe outcome for both baby and mother. The safety and optimal outcome for one is often linked to, but not always directly related to, the other and conflict may arise. The natural desire of mothers to put their babies health before their own can be hard for clinicians to ignore, nor should they, but the anticipated morbidity and mortality for both mother and baby must be carefully weighed and considered in the often urgent actions we take at delivery of these infants. Underpinning these decisions should be the conscientious use of current research and evidence to make decisions about care. In 1989, Penn et al. designed a randomised controlled trial aiming to address one such obstetric unknown; the optimal mode of delivery of the preterm infant presenting in the breech position. At the time of trial conception, common practice dictated that the premature infant should be delivered via caesarean section. The surgery is associated with risk of complications for the mother, particularly at early gestations when the lower uterine segment may not be well formed and the classical technique may be required, as well as carrying risk to future pregnancies, but it is unclear whether caesarean or vaginal delivery is safest for the preterm baby. Before study conception, existing practice was influenced by observational retrospective data subject to significant bias and particularly by clinician ‘preference’. For example, the preterm infant born vaginally may have presented in more advanced labour when the benefit of corticosteroids may be lost, or be at extremes of viability such that a clinician may be disinclined to perform a caesarean section, falsely suggesting that vaginal delivery is dangerous. Alternatively, fetal distress in labour may result in both a caesarean section, and an infant born in poor condition, therefore favouring vaginal delivery. Nevertheless, at the time this study was considered, it was common practice to perform a caesarean section for these premature infants with the aim of avoiding presumed neonatal morbidity (to avoid the ‘stress’ of labour and risk of cervical head entrapment) despite the likely increased maternal morbidity. On this background in 1975 the Royal College of Obstetricians and Gynaecologists (RCOG) recommended a randomised controlled trial to address this issue, taken up by Penn et al. in 1989. Women in labour between 26 and 32 weeks of gestation with a singleton live pregnancy in breech presentation and

A Multicenter Cohort Study of Histologic Findings and Long-Term Outcomes of Kidney Disease in Women Who Have Been Pregnant

BACKGROUND AND OBJECTIVES For many women pregnancy is the first contact with health services, thus providing an opportunity to identify renal disease. This study compares causes and long-term renal outcomes of biopsy-proven renal disease identified during pregnancy or within 1 year postpartum, with nonpregnant women. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Native renal biopsies (1997-2012), in women of childbearing age (16 to <50 years), from 21 hospitals were studied. The pregnancy-related diagnosis group included those women with abnormal urinalysis/raised creatinine identified during pregnancy or within 1 year postpartum. Pregnancy-related and control biopsies were matched for age and ethnicity (black versus nonblack). RESULTS One hundred and seventy-three pregnancy-related biopsies (19 antenatal, 154 postpregnancy) were identified and matched with 1000 controls. FSGS was more common in pregnancy-related biopsies (32.4%) than controls (9.7%) (P<0.001) but there were no differences in Columbia classification. Women with a pregnancy-related diagnosis were younger (32.1 versus 34.2 years; P=0.004) and more likely to be black (26.0% versus 13.3%; P<0.001) than controls, although there were no differences in ethnicities in women with FSGS. The pregnancy-related group (excluding antenatal biopsies) was more likely to have a decline in Chronic Kidney Disease Epidemiology Collaboration eGFR in the follow-up period than the control group (odds ratio, 1.67; 95% confidence interval, 1.03 to 2.71; P=0.04), and this decline appeared to be more rapid (-1.33 versus -0.56 ml/min per 1.73 m2 per year, respectively; P=0.045). However, there were no differences between groups in those who required RRT or who died. CONCLUSIONS Pregnancy is an opportunity to detect kidney disease. FSGS is more common in women who have been pregnant than in controls, and disease identified in pregnancy or within 1 year postpartum is more likely to show a subsequent decline in renal function. Further work is required to determine whether pregnancy initiates, exacerbates, or reveals renal disease.

The Effect Of Labetalol And Nifedipine MR On Blood Pressure In Women With Chronic Hypertension In Pregnancy

AIM To compare the blood pressure (BP) lowering effects of labetalol and nifedipine modified release (MR) in hypertensive pregnant women. We also investigated the effect on the heart rate (HR) and determined the proportion of time spent in target. METHODS This was an exploratory study. Women with chronic hypertension taking either labetalol or nifedipine were offered 24-h ambulatory blood pressure monitoring (ABPM). Sleep, wake and drug ingestion times were self-reported. An indirect response model was used to analyse the systolic BP (SBP), diastolic BP (DBP) and HR time-series; the effect of gestation and type of drug was evaluated. RESULTS Forty-eight women were recruited: 24 in each group. There was no difference in clinical characteristics. In women taking nifedipine there was a positive association between the dose of nifedipine and pre-dose BP p = .002, this was not present in the labetalol group. There was a difference between the drug effects on both the SBP and DBP time-series (p = .014). In comparison to labetalol, there was less variation in day time BP in those women prescribed nifedipine. Women on labetalol spent a larger proportion of time with their DBP below target (<80 mmHg). The HR dynamics were qualitatively different, a stimulatory effect was found with nifedipine compared to an inhibitory effect with labetalol. CONCLUSION There are significant and important differences between the BP lowering effects of nifedipine and labetalol. A large randomised control trial is required to investigate the relationship between BP variability and time in target on pregnancy outcomes.

The challenges of licensing drugs for use in pregnancy

Most recommended obstetric therapeutic agents are not licensed for their purpose. There is a lack of funding for research and little development of new therapeutic agents for use in the treatment of pregnancy-related disorders. Current therapeutics used in maternal health and their licensing status are reviewed and suggestions for these shortfalls together with possible solutions considered.

The impact of ethnicity on adverse perinatal outcome in women with chronic hypertension: a cohort study: Ethnicity and chronic hypertension in pregnancy

To assess the impact of maternal ethnicity on the risk of adverse perinatal outcome in pregnant women with chronic hypertension.