Cognitive outcome in childhood of birth weight discordant monochorionic twins: the long-term effects of fetal growth restriction.

AIM: Intrauterine growth restriction (IUGR) is associated with poorer outcomes in later life. We used a monochorionic twin model with IUGR in one twin to determine its impact on growth and neurocognitive outcomes. METHODS: Monochorionic twins with ≥20% birth weight discordance born in the north of England were eligible. Cognitive function was assessed using the British Ability Scales. The Strength and Difficulties Questionnaire was used to identify behavioural problems. Auxological measurements were collected. Generalised estimating equations were used to determine the effects of birth weight on cognition. RESULTS: Fifty-one monochorionic twin pairs were assessed at a mean age of 6.3 years. Mean birth weight difference was 664 g at a mean gestation of 34.7 weeks. The lighter twin had a General Conceptual Ability (GCA) score that was three points lower (TwinL -105.4 vs TwinH -108.4, 95% CI -0.9 to -5.0), and there was a significant positive association (B 0.59) of within-pair birth weight differences and GCA scores. Mathematics and memory skills showed the largest differences. The lighter twin at school age was shorter (mean difference 2.1 cm±0.7) and lighter (mean difference 1.9 kg±0.6). Equal numbers of lighter and heavier twins were reported to have behavioural issues. CONCLUSIONS: In a monochorionic twin cohort, fetal growth restriction results in lower neurocognitive scores in early childhood, and there remain significant differences in size. Longer term follow-up will be required to determine whether growth or cognitive differences persist in later child or adulthood, and whether there are any associated longer term metabolic sequelae.

The North of England Survey of Twin and Multiple Pregnancy.

The population-based Northern Survey of Twin and Multiple Pregnancy (NorSTAMP, formerly the Multiple Pregnancy Register) has collected data since 1998 on all multiple pregnancies in North of England (UK) from the earliest point of ascertainment in pregnancy. This paper updates recent developments to the NorSTAMP and presents some early mortality data from the first 10 years of data collection (1998-2007). Since 2005, mothers have been asked to give explicit consent for their identifiable data to be held by the survey, in line with changing guidance and legal frameworks for identifiable data. In 2009, regional standards of care for multiple pregnancies were developed, agreed, and disseminated. During 1998-2007, 4,865 twin maternities (pregnancies with at least one live birth or stillbirth) were registered, with an average twinning rate of 14.9 per 1,000 maternities. The overall stillbirth and neonatal mortality rates in twins were 18.0/1,000 births and 23.0/1,000 live births respectively. Stillbirth and neonatal mortality rates were significantly higher in monochorionic than dichorionic twins: 44.4 versus 12.2 per 1,000 births (relative risk [RR] 3.6, 95% Confidence Intervals [CI] 2.6-5.1), and 32.4 versus 21.4 per 1,000 live births (RR 1.5, 95% CI 1.04-2.2) respectively. There was no significant improvement during this period in either stillbirth or neonatal mortality rates in either chorionicity group. This population-based survey is an important source of data on multiple pregnancies, which allows monitoring of trends in multiple birth rates and pregnancy losses, providing essential information to support improvements in clinical care and for epidemiological research.

Stillbirth and neonatal mortality in monochorionic and dichorionic twins: a population-based study.

BACKGROUND: Chorionicity is one of the main predictors of higher perinatal mortality in twins. The aim of this large population-based study was to analyse stillbirth and neonatal mortality by cause of death and chorionicity and to quantify the risk of stillbirth by gestational age in dichorionic (DC) and monochorionic (MC) twins. METHODS: We used data on twin maternities delivered in the North of England from 1998 to 2007 and notified to the Northern Survey of Twin and Multiple Pregnancy. Prospective risk of stillbirth by gestational age at death was calculated using number of stillborn fetuses at or beyond a given gestational period per 1000 fetuses in ongoing pregnancies. RESULTS: There were 4565 twin maternities (9130 twins) with an overall twinning rate of 14.9 per 1000 maternities. The overall stillbirth and neonatal mortality rates in twins during 1998-2007 were 18.0/1000 births and 23.0/1000 live births, respectively. Stillbirth and neonatal mortality rates were significantly higher in MC than DC twins: 44.4 versus 12.2 per 1000 births [relative risk (RR): 3.6; 95% CI: 2.6-5.1], and 32.4 versus 21.4 per 1000 live births (RR: 1.5; 95% CI: 1.04-2.2), respectively. There was no significant improvement over time in either stillbirth or neonatal mortality rates in either group. The prospective risk of antepartum stillbirth was higher for MC than DC twins at all preterm gestations and the highest risk was before 28 weeks' gestation. CONCLUSIONS: MC twins have higher rates of stillbirth and neonatal mortality than DC twins, and rates did not improve over 1998-2007. The prospective risk of antepartum stillbirth is much higher for MC twins at all gestational ages.

Progesterone for the prevention of preterm birth in twin pregnancy (STOPPIT): a randomised, double-blind, placebo-controlled study and meta-analysis.

BACKGROUND: Women with twin pregnancy are at high risk for spontaneous preterm delivery. Progesterone seems to be effective in reducing preterm birth in selected high-risk singleton pregnancies, albeit with no significant reduction in perinatal mortality and little evidence of neonatal benefit. We investigated the use of progesterone for prevention of preterm birth in twin pregnancy. METHODS: In this double-blind, placebo-controlled trial, 500 women with twin pregnancy were recruited from nine UK National Health Service clinics specialising in the management of twin pregnancy. Women were randomised, by permuted blocks of randomly mixed sizes, either to daily vaginal progesterone gel 90 mg (n=250) or to placebo gel (n=250) for 10 weeks from 24 weeks' gestation. All study personnel and participants were masked to treatment assignment for the duration of the study. The primary outcome was delivery or intrauterine death before 34 weeks' gestation. Analysis was by intention to treat. Additionally we undertook a meta-analysis of published and unpublished data to establish the efficacy of progesterone in prevention of early (<34 weeks' gestation) preterm birth or intrauterine death in women with twin pregnancy. This study is registered, number ISRCTN35782581. FINDINGS: Three participants in each group were lost to follow-up, leaving 247 analysed per group. The combined proportion of intrauterine death or delivery before 34 weeks of pregnancy was 24.7% (61/247) in the progesterone group and 19.4% (48/247) in the placebo group (odds ratio [OR] 1.36, 95% CI 0.89-2.09; p=0.16). The rate of adverse events did not differ between the two groups. The meta-analysis confirmed that progesterone does not prevent early preterm birth in women with twin pregnancy (pooled OR 1.16, 95% CI 0.89-1.51). INTERPRETATION: Progesterone, administered vaginally, does not prevent preterm birth in women with twin pregnancy. FUNDING: Chief Scientist Office of the Scottish Government Health Directorate.

Monozygotic triplet pregnancy following egg donation and transfer of single frozen-thawed embryo.

OBJECTIVE: To describe a case of monozygotic triplet pregnancy following egg donation and the transfer of a single frozen-thawed embryo. DESIGN: Case report. SETTING: District general hospital and regional department of fetal medicine in northeast England. PATIENT(S): A 38-year-old woman with a 2-year history of primary infertility due to severe endometriosis and poor ovarian reserve who conceived after egg donation and transfer of a single frozen-thawed embryo. INTERVENTION(S): Transfer of a single frozen-thawed embryo and delivery of three identical female infants by emergency caesarean section because of preterm labor at 32 weeks' gestation. MAIN OUTCOME MEASURE(S): Review of effect of assisted conception on monozygotic twinning rates. RESULT(S): Healthy outcome for all three infants. CONCLUSION(S): Assisted reproductive treatments may lead to disturbances in zona pellucida architecture and an increase in monozygotic twinning rates. Couples need to be informed of this and the increased risks associated with these pregnancies before they begin with treatment.

PLUTO trial protocol: percutaneous shunting for lower urinary tract obstruction randomised controlled trial.

OBJECTIVES: The primary objective is to determine whether intrauterine vesicoamniotic shunting for fetal bladder outflow obstruction, compared with conservative, noninterventional care, improves prenatal and perinatal mortality and renal function. The secondary objectives are to determine if shunting for fetal bladder outflow obstruction improves perinatal morbidity, to determine if improvement in outcomes is related to prognostic assessment at diagnosis and, if possible, derive a prognostic risk index and to determine the safety and long-term efficacy of shunting. DESIGN: A multicentre randomised controlled trial (RCT). SETTING: Fetal medicine units. POPULATION: Pregnant women with singleton, male fetus with isolated lower urinary tract obstruction (LUTO). METHODS: Following ultrasound diagnosis of LUTO in a male fetus and exclusion of other structural and chromosomal anomalies, participation in the trial will be discussed with the mother and written information given. Consent for participation in the trial will be taken and the mother randomised via the internet to either insertion of a vesicoamniotic shunt or expectant management. During pregnancy, both groups will be followed with regular ultrasound scans looking at viability, renal measurements and amniotic fluid volume. Following delivery, babies will be followed up by paediatric nephrologists/urologists at 4-6 weeks, 12 months and 3 and 5 years to assess renal function via serum creatinine, renal ultrasound and need for dialysis/transplant. MAIN OUTCOME MEASURES: The main outcome measures will be perinatal mortality rates and renal function at 4-6 weeks and 12 months measured via serum creatinine, renal ultrasound and need for dialysis/transplant. FUNDING: Wellbeing of Women. ESTIMATED COMPLETION DATE: September 2010. TRIAL ALGORITHM: [flowchart: see text].

Management of small-for-gestational-age twins with absent/reversed end diastolic flow in the umbilical artery: outcome of a policy of daily biophysical profile (BPP).

OBJECTIVES: To evaluate a strategy of daily biophysical profile (BPP) for pregnancies with small-for-gestational-age twins and with absent or reversed end diastolic flow (AREDF) in the umbilical artery of one twin and to assess the latency interval between detection and delivery in monochorionic (MC) and dichorionic (DC) twin pregnancy. METHODS: A search of the Fetal Medicine Database was carried out between 2000 and 2005 at a single tertiary centre to identify all cases with AREDF in the umbilical artery with one small-for-gestational-age twin. Active monitoring with daily BPP was undertaken, once the estimated fetal weights (EFW) was >or= 500 g and at a gestational age of >or= 24 weeks in both twins. Delivery was timed on the basis of an abnormal BPP, two equivocal BPP within 12 h or gestational age of >or= 32(+0) weeks. RESULTS: Twenty-two MC and 17 DC twin pregnancies were identified. There were no fetal losses in the viable actively monitored MC (19) and DC (13) twins. There was a longer latency interval in the MC group at 21.7 days versus 14.4 days in the DC group (p = 0.13). Delivery was indicated for an abnormal BPP (57.8% MC vs 30.8% DC). CONCLUSIONS: A strategy of daily BPP can be used to monitor preterm twin fetuses with AREDF, prolonging pregnancy with an acceptable perinatal outcome.

Population-based outcomes after acute antenatal transfer.

Acute antenatal transfer to specialist centres is an accepted practice but few or no regular data are collected regarding the numbers of transfers performed or subsequent pregnancy outcome. We wished to determine the numbers, and the maternal and fetal outcomes following acute antenatal transfer between consultant obstetric units in the former Northern Region of the UK over a 12-month period (1 January-31 December 99). This is a geographically defined population in terms of provision of perinatal services. All acute antenatal transfers were notified centrally. Data pertaining to each transfer were collected at the time of transfer. Subsequent maternal and fetal outcomes were determined from patient records and neonatal databases. The regional annual acute antenatal transfer rate was 3.7 per 1000 deliveries. Most were for fetal reasons, although transfer rates varied between hospitals. The decision to transfer was influenced by distance and availability of paediatric staff. Even units that have similar characteristics show considerable variation in their transfer rates. No adverse incidents occurred during transfer and no major changes in maternal management occurred following transfer. Twenty-four per cent of women remained undelivered following transfer. Women with preterm labour in the absence of ruptured membranes were less likely to deliver than those transferred for other reasons and if they did deliver, their infants were also less likely to need intensive care. We believe audit of acute antenatal transfers should be routinely undertaken. Numbers of transfers might be reduced if delivery and the need for neonatal intensive care could be predicted with greater accuracy. The psychological and financial costs of transfer to women and healthcare providers need to be addressed.

A multiple pregnancy register in the north of England.

A regional population-based Multiple Pregnancy Register was established in 1998, with the aim of collecting detailed information on multiple pregnancies to enable research into mortality and morbidity in multiples. Multiple pregnancies are notified to the Register as soon as they are detected, irrespective of whether they resulted in a spontaneous abortion, termination of pregnancy or registered birth. Nine hundred and twenty-six twin pregnancies were recorded during 1998-99, giving a twinning rate of 14.8 per 1000 maternities (rate at birth 13.0 per 1000 maternities). Sixty one per cent of twin pregnancies were detected before 13 weeks of gestation. Chorionicity was determined in 82.6% of 849 twin maternities with at least one stillbirth or livebirth. The fetal loss rate before 24 weeks of gestation was 10.5% (194/1852). The perinatal and infant mortality rates were 40.6 per 1000 births and 32.6 per 1000 livebirths respectively. A prospective Multiple Pregnancy Register not only allows monitoring of trends in multiple birth rates and mortality, but also etiological research and long-term follow-up studies.