Stephen Sturgiss

MATERNAL UNIPARENTAL DISOMY FOR CHROMOSOME 2 IN ASSOCIATION WITH CONFINED PLACENTAL MOSAICISM FOR TRISOMY 2 AND SEVERE INTRAUTERINE GROWTH RETARDATION

We report a liveborn infant with severe intrauterine growth retardation and renal failure, delivered following detection of non‐mosaic trisomy 2 by chorionic villus biopsy in the first trimester. Detailed analysis post‐delivery indicated apparent complete trisomy 2 of the chorionic tissues, with a chromosomally normal infant demonstrating maternal uniparental disomy for chromosome 2.

Renal Abnormalities on Obstetric Ultrasound as a presentation of DiGeorge Syndrome

We describe three pregnancies that presented with renal anomalies on obstetric ultrasound as the main abnormality and were subsequently found to have interstitial deletions within chromosome 22q11. A cardiac defect, double‐outlet right ventricle, was also seen in the first case. Amnio infusion was refused in the second pregnancy and the perimembranous ventricular septal defect was not identified prior to termination. In the third case, there was no cardiac defect. The genitourinary abnormalities were a right hydroureter and hydronephrosis with a ureterocele bulging into the bladder lumen, bilateral multicystic kidneys with associated oligohydramnios, and a left multicystic kidney with right renal agenesis and associated oligohydramnios. Absence of thymus at autopsy in all three cases led to fluorescent in situ hybridization studies looking for the submicroscopic deletion of chromosome 22q11 associated with DiGeorge syndrome.

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.

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.

Fetal hepatic necrosis following blood sampling from the intrahepatic vein

Previous reports have suggested that fetal blood sampling from the intrahepatic vein is not associated with significant fetal hepatic injury. We report a case of fetal liver necrosis occurring 24 h following blood sampling from the intrahepatic vein of a fetus with severe growth retardation at 34 weeks. The placenta was in a posterior position, precluding either blood sampling from the placental insertion or placental biopsy. Fetal death occurred in utero within 24 h of the procedure, which was carried out by an experienced operator. At post‐mortem the liver appeared normally formed, but the right lobe was diffusely congested, with a well‐defined demarcation line between the right and left lobes. Liver histology revealed extensive recent haemorrhagic necrosis of the right lobe.

ABSENT-END-DIASTOLIC FLOW VELOCITY IN THE UMBILICAL ARTERY

Fetal growth restriction (FGR) as a consequence of uteroplacental insufficiency is an important contributor to perinatal death, neonatal morbidity and long-term health problems. Progressive uteroplacental dysfunction leads to placental respiratory failure and fetal hypoxaemia, which triggers compensatory fetal haemodynamic changes including blood flow redistribution towards essential fetal organs (brain, heart and adrenal glands) at the expense of the other body systems. The duration of the compensatory phase is variable, sometimes lasting weeks, and appears not to have deleterious short-term consequences. With further disease progression, the compensatory mechanisms reach their limit and myocardial dysfunction occurs. Once the disease enters this decompensatory phase, the fetus is at high risk of multisystem organ failure and in-utero demise. There is no effective in-utero therapeutic intervention. The main aim of management is to deliver the baby when the risks of antenatal demise and irreversible end-organ dysfunction associated with further prolongation of the pregnancy are greater than the risks from delivery.

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.

Prevalence, antenatal management and perinatal outcomes of monochorionic monoamniotic twin pregnancies: a collaborative multicentre study in England, 2000‐2013

To determine the prevalence of monochorionic monoamniotic (MCMA) twin pregnancy and to describe perinatal outcome and clinical management of these pregnancies.

Effect of Pregnancy on Long-Term Function of Renal Allografts

Pregnancy in renal allograft recipients is associated with hyperfiltration with the potential for glomerular damage and adverse effects on long-term graft prognosis. We have undertaken a case-controlled study of posttransplant follow-up for a mean of 12 years (range, 4 to 23) in 36 female renal allograft recipients, 18 who became pregnant and 18 controls (matched to underlying disease and renal function) who did not. Assessments included plasma creatinine (PCr), glomerular filtration rate (GFR) by infusion clearance of inulin (Cin), mean arterial pressure (MAP), and documentation of antihypertensive therapy. By the end of follow-up, PCr in the pregnancy group (112 +/- 73 mumol/L [1.26 +/- 0.83 mg/dL]) and controls (127 +/- 52 mumol/L [1.44 +/- 0.59 mg/dL]) had increased by 19% and 8%, respectively, and GFR in the pregnancy group (58 +/- 29 mL/min) and controls (56 +/- 32 mL/min) had decreased by 18% and 7%, respectively. Graft loss or chronic rejection occurred in two patients in each group and there was a death in the pregnancy group 9 years after the second of two successful pregnancies. MAP in the pregnancy group (96 +/- 12 mm Hg) had decreased by 1%, and in the controls (101 +/- 9 mm Hg) had increased by 5%. Two patients in the index group and three in the control group commenced antihypertensive therapy during follow-up. There was, therefore, no evidence of an adverse effect of pregnancy in renal allograft recipients on long-term renal function or development of hypertension.