OG SURVEY - OBSTETRICS

1. PATIENT SAFETY AND LABOUR WARD SIZE: IS BIGGER BETTER? (MARCH 2014)Milland M. Acta OG Scand 2013;92:12171 - 12176This study from Denmark looked at the safety of birth units by using negligence claims as an index. They reviewed claims made to and claims accepted by the Danish Patient Insurance Association over the 15 years 1995 – 2009 inclusive.

The findings were: The overall number of claims made was 1.5 per 1000

o Claims made were not significantly different between birth units of varying sizes The overall rate of claims substantiated by the DPIA was 40% (0.6 per 1000)

o Claims substantiated varied with birth unit size :Births per year Claims Substantiated

3000 – 4000 34% LOWEST > 4000 39% 1000 – 3000 42% < 1000 50% HIGHEST

Previous studies have also found that small hospitals have higher rates of maternal and neonatal morbidity, including birth asphyxia, because they lack speedy access to OT and paediatricians after hours.

On the other hand, the largest units may also be vulnerable when times of peak patient volumes throw up multiple competing emergencies which overwhelm the otherwise adequate available services. The Editor cites Parkland Hospital in Dallas Texas, the largest maternity unit in the USA, which has divided its maternity service into 3 units, each managing approximately 5000 of the total 15,000 births because the staff have decided such a division makes pregnancy care both more manageable and safer.

ConclusionWhile the optimal size of a birthing service is not known, it appears that both the smallest units and the largest ones have potential vulnerabilities with respect to outcomes including birth asphyxia.

2. IMPACT OF UNIVERSAL CORD BLOOD GASES AND LACTATE AT DELIVERY (JUNE 2014)White CRH. ANZJOG 2014; 54:71 - 78This group from WA has previously shown an improvement in neonatal outcomes after the introduction of cord blood gas assessment for all deliveries in a tertiary unit. The current study looks at universal ABG or cord lactate at 3 smaller units, which had 1000 – 3300 births at each site over an 18 – 24 months period.

The two smaller units utilised cord lactate assessment (using a hand held meter) rather than formal ABGs and found a significant reduction in abnormal results over time.

For example, at Unit A Cord arterial lactate > 6.7 fell from 8.5% 2.8% of births Cord arterial lactate > 6.1 fell from 16% 8%

Similar reductions occurred at the other two units. Interestingly, there were no significant changes in the rates of caesarean section or instrumental birth over the study period. The mechanism for improvement in outcomes is therefore not clear although immediate objective feedback to staff provided by routine cord gases plays a role in labour management. Of interest, Apgar scores did not change over the study period.

ConclusionUniversal umbilical cord arterial gas assessment is associated with reduced cord blood measures of neonatal acidosis. Cord lactate appears to be as useful as formal cord ABGs and is more cost effective.

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3. MISCARRIAGE MANAGED BY D&C INREASES RISK OF SPONTANEOUS PRETERM BIRTH (MARCH GYNAE 2014) McCarthy FP and SCOPE Consortium. Hum Reprod 2013;28:3197-3206. The aim of this international cohort study group (which included Gus Dekker from Adelaide) was to determine whether :

Women with a previous miscarriage or termination of pregnancy are at increased risk of spontaneous preterm birth (SPTB)

There is any increased risk of prior cervical dilation and uterine curettage (D&C) compared to medical methods of pregnancy evacuation

Prospective data were collected on nearly 5600 nulliparous women with a singleton pregnancy who were enrolled between 2004 – 2011. 78% had no previous pregnancy loss (miscarriage or termination), 17.5% had one loss, 4.5% had two losses and 0.5% had 3 or 4 losses.

The findings were A single prior pregnancy loss was not associated with an increase in SPTB 2 to 4 prior losses were associated with an increase in SPTB with aOR 2.1 Compared to women with no prior loss:

o The use of D&C to manage a prior miscarriage or termination was associated with an increased risk of SPTB (aOR 1.6 for miscarriage, aOR 1.8 for termination)

o The use of medication to manage a prior miscarriage or termination was not associated with an increased risk of SPTB (aOR 0.86 for miscarriage and 0.87 for termination)

The current findings do not constitute a definite causality between D&C and future SPTB but do raise concerns which need to be addressed by future prospective studies.

ConclusionA single pregnancy loss managed by D&C was associated with an increased risk of SPTB. In contrast, a single pregnancy loss managed nonsurgically was not associated with an increased risk of SPTB. However, 2 to 4 losses were associated with increased risk. Further studies are needed to explore this possible association.

4. PREGNANCY TERMINATION AND MENTAL HEALTH (JUNE GYNAE 2014) Steinberg JR. Obstet Gynecol 2014;123:263 – 270. A previous study from the USA found a strong association between termination of pregnancy and several post-termination mental health disorders. However, the authors corrected only for socio-demographic factors and not for the effects of pregnancy itself or for pre-pregnancy mental health disorders.

In this current study, also from the USA, cohort data were obtained using structured psychiatric interviews among 260 women after first termination of pregnancy and 700 women after first childbirth.

The percentage of women with mental health disorders before first termination was significantly higher than before first pregnancy and, after correcting for these, there were no differences in the following 5 disorders: anxiety, mood, impulse control, eating disorder and suicidal ideation. Only substance abuse was more common in the women having first termination compared to first birth (hazard ratio = 3).

ConclusionPre-pregnancy mental health was a strong predictor of post-pregnancy mental health. After controlling for confounding factors, termination of pregnancy was not a statistically significant predictor of post-pregnancy anxiety, mood, impulse-control, eating-disorder or suicidal ideation.

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5. BIRTH – VBAC RISK AND SONOGRAPHIC MEASUREMENT OF LOWER SEGMENT THICKNESS: A META-ANALYSIS (MARCH 2014) Kok N. Ultrasound OG 2013;42:132-139. Get StudyThe risk of catastrophic uterine rupture during a VBAC attempt limits the number of women who make such an attempt. The rupture risk is increased with oxytocin use, short inter-delivery interval, prior chorioamnionitis and more than one previous CS but even then the risk is low with over 98% of women having a trial of labour not experiencing rupture. How to better refine the groups at low and high risk?

Over the years a number of ultrasound studies have looked at the correlation between the lower uterine segment (LUS) thickness on ultrasound in the late third trimester (34 – 39 weeks) and the presence of a lower uterine segment defect after at or after delivery. This study from The Netherlands is a meta-analysis of such research. After reviewing the available literature, 21 cohort studies involving nearly 2800 women were included. While the studies were high quality, there was considerable heterogeneity in measurement ranges, techniques and outcomes. The overall VBAC rate in the studies reviewed varied from 19 – 68% (number of successful VBAC/number of all women with a previous CS) with the success rate in those attempting a trial of labour ranging from 20 – 78% (number of successful VBAC/number attempting VBAC).

Defects were defined as including both dehiscence and scar rupture.

Uterine scar dehiscence was defined as Loss of continuity of the myometrial layer without complete rupture of the lower uterine segment (LUS),

a so-called uterine ‘window’. Rupture was defined as

Complete separation of the uterine scar resulting in communication between the uterine and peritoneal cavities.

NOTE: True rupture was rare while dehiscence was more common

Full LUS thickness was defined as The distance between the bladder wall and the amniotic cavity; this was measured by placing one

caliper at the interface between urine and bladder wall the other at the interface between amniotic fluid and decidual endometrium.

Myometrial thickness was defined as The minimum thickness overlying the amniotic cavity at the level of the uterine scar and with only the

myometrium being measured.

The findings were (note, these were from many studies, each using different thickness cut-offs):

Full LUS thickness ≤ 2 – 3mm and risk of defect during or immediately after birtho 61% Sensitivity o 91% Specificity

Full LUS thickness ≤ 3.1 – 5.1mm and risk of defect during or immediately after birtho 96% Sensitivity o 63% Specificity

Note: No comparison regarding TA v TV scan could be made on the basis of the available data. Full thickness and myometrial thickness LUS had similar predictive values (though different numbers)

ConclusionThere is a strong negative relationship between third trimester ultrasound lower uterine thickness and the risk of a defect at or just after birth when a trial of labour is attempted. The studies in the meta-analysis used a mix of approaches (TV scan, TA scan, both TA and TV) and a range of thickness cut-offs.

NOTE: While such ultrasound measurements appears promising in the planning of VBAC, before LUS measurements can be adopted the following must occur:

Standardisation of the measurement techniqueo Which part of lower segmento TA v TVo Myometrium only v full thickness

Validation of the standardised approach (as occurred with TV scan assessment of cervical length)

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6. BIRTH – OUTCOMES OF TERM IOL FOR SGA (APRIL 2014) Ofir K. Eur J OG Rep Biol 2013;171:257-261. Babies with suspected IUGR are commonly induced at 37 – 9 weeks to reduce the risk of stillbirth and other morbidity. But ‘early term’ delivery is associated with worse longer term outcomes, including cognitive performance, than being born after 39 weeks. This retrospective study from Israel looked at 2400 babies who were born SGA according to birth weight, corrected for sex (6.4% of neonates). The researchers compared outcomes for the 400 where IUGR was suspected in utero leading to induction at 37 – 9 weeks with the 2000 SGA babies who were not induced.

The results were Higher rates of jaundice needing phototherapy (aOR 1.8 SIG) and hypoglycaemia (aOR 2.4 SIG) in

the IOL group while 2 neonates in the IOL group had respiratory complications. All other neonatal outcomes were similar between the two groups. No neonates died. There were 33 stillbirths in the whole birth cohort of 37,000 singletons ≥ 37 weeks (0.88 per 1000) of

which only one was SGA (stillbirth at 37 weeks).

While this is a retrospective study, a previous large RCT (n = 320 each arm) has also looked at this issue, randomising suspected IUGR pregnancies ≥ 36 weeks to IOL or expectant management with fetal surveillance.

On average, the IOL group were delivered 10 days earlier and were 130g smaller. There was no difference in outcomes of perinatal wellbeing with the composite index (mortality, cord

pH, Apgars, NICU admission) being 6% in both groups. There was also no difference in the CS rate which was 14% in both groups. The study was underpowered to detect a significant difference in stillbirth rates while there was a

higher rate of SCN admission (48% v 36%) in the IOL group. (DIGITAT from Europe BMJ 2010;341:c7087).

ConclusionWhen planning IOL between 37 and 39 weeks for suspected SGA, an obstetrician should take into account the possible small increase in neonatal morbidity associated with such a decision.

7. BIRTH – SUBSEQUENT PREGNANCY OUTCOMES AFTER PLANNED versus EMERGENCY CAESAREAN IN THE FIRST BIRTH (MAY 2014) Kok N. BJOG 2014;121:216-223. Using the Dutch Perinatal Registry, outcomes for second births after prior caesarean delivery were analysed comparing prior planned caesarean delivery (pCD, ie elective) with prior emergency caesarean delivery (eCD). 75% of the prior pCD had been for breech presentation.

11,000 women had prior pCD and 30,000 had prior eCD.

Outcomes in next birth were Prior pCD Prior eCD Uterine rupture in trial of labour 0.3% 0.2% NS Stillbirth 4.8 per 1000 3.2 per 1000 Sig Prematurity 4.3% 3.8% Sig PPH 5.8% 5.0% Sig Composite adverse maternal outcomes 6.0% 5.2% Sig Composite adverse neonatal outcomes Equivalent

ConclusionThe results show a small increase in PPH, stillbirth and uterine rupture in the next birth after prior planned CD compared to emergency CD. Previous studies have shown an increased rate of accreta in the next pregnancy after a prior elective versus emergency caesarean. Whether this has implications for practice (most elective caesareans have a valid indication) is unclear.

8. PRETERM BIRTH PREVENTION – GENERAL COMMENTS (MAY 2014) Iams JD. NEJM 2014;370:254 - 361 This is a review article looking at the management of a theoretical woman with two previous preterm births – 30 weeks and 19 weeks. It examines the role of

Routine progesterone until 36 weeks Fortnightly cervical screening between 16 – 24 weeks (weekly if CL < 30mm) Consideration of cerclage if TV CL < 25mm before 24 weeks of gestation.

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9. PRETERM BIRTH PREDICTION – CERVICAL LENGTH U/S MEASUREMENT IN MIDPREGNANCY: TA versus TV LENGTH. (MARCH 2014) Roh HJ. J Ultrasound Med 2013;32:1721-1728 The risk of delivering preterm is inversely related to the cervical length (CL) as measured on transvaginal (TV) scan at 18 – 24 weeks. Several studies have now shown that vaginal progesterone therapy administered to women with CL < 20 mm can reduce the preterm birth risk by about 50%.

While there is economic modelling suggesting a possible cost benefit (depending on the cost of the scan and the efficacy of progesterone), adding a TV scan to every morphology scan in low risk women is time consuming and expensive. There is therefore considerable interest in the efficacy of CL assessment by transabdominal (TA) versus TV scan. A previous study showed that a TA CL ≤ 35mm detected 100% of TV CL ≤ 20mm.

In this study from Korea, 315 women having a TV CL between 20-30 weeks also had a TA CL attempted. 50 had unsuccessful TA CL because the internal os could not be visualised 65 had 4mm discrepancy between TA CL and TV CL when the internal but not the external os could

be visualised 190 had negligible discrepancy between TA and TV CL when both internal and external os were

visualised (mean TA CL 38.8mm and mean TV CL 39.3mm) The TA CL tended to be slightly shorter than TV CL

ConclusionThe study suggests that TA CL as the initial screen is reasonable with TV CL undertaken if the view is not adequate. What needs to happen now is a large study looking at whether routine TV CL offers any benefit compared to TA CL with reflex performance of TV CL only when indicated.

10. PRETERM BIRTH PREVENTION – PRENATAL HOME VISITING IN AT-RISK FIRST-TIME MOTHERS (MARCH 2014) Goyal NK. Pediatrics 2013;132:S118-S125 In the USA about 4 million babies are born annually with 1 in 8 or 500,000 being born prematurely. Socially disadvantaged women are significantly more likely to deliver preterm and also to have SGA babies.

This retrospective cohort study from Ohio between 2007 - 2010 looked at the effect of prenatal home visits during the first and second trimesters of pregnancy on preterm birth and SGA rates among socially disadvantaged women in their first ongoing pregnancy.

The results were: Compared to the reference group of ≤ 3 home visits: Completion of ≥ 8 home visits by 26 weeks was associated with an adjusted odds ratio of 0.38 for

preterm birth (sig) Completion of ≥12 home visits by 26 weeks was associated with an adjusted odds ratio of 0.32 for

having an SGA baby (sig)

ConclusionIn a non-randomised study, an intensive prenatal home visit program among at-risk first time mothers significantly reduced (by about two-thirds) the risk of both preterm birth and SGA.

11. PRETERM BIRTH ASSOCIATION – POOR AIR QUALITY AND RISK FOR PRETERM BIRTH (MAY 2014) Pereira G. Am J Epidemiol 2014;179:67 - 74 Causes of or associations with preterm birth are constantly sought and this study from the USA looked at the association of poor air quality (fine particulate material in the air) with preterm birth.

The findings were An association between poor air quality and preterm birth was found

o There was a small increase in preterm birth overall in women exposed to poor air qualityo There was a large increase in preterm birth in Hispanic women exposed to poor air quality

ConclusionAn association was found between poor air quality and preterm birth. This could be due to substantial confounding (eg poverty). Alternatively, the air quality may have direct toxic effects on the pregnancy or could induce harm via proinflammatory changes. Further study is needed.

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12. PREGNANCY OUTCOME – ROUTINE T3 ULTRASOUND: A RCT (APRIL 2014) Skrastad RB. Acta OG Scand. 2013;92:1353 – 1360.

Our current screening test for fetal growth disorders, the fundal height assessment, is a poor tool for detecting SGA, with a sensitivity of only 20-40%. This RCT from Norway (conducted 1989 -1992 but published in 2013, not clear why) allocated approx. 3200 women to routine care and approx. 3200 women to an extra ultrasound at 33 weeks gestation to assess for growth disorders.

The definition of SGA is different from what we would use now (and a bit confusing). They defined SGA as more than -5% growth deviation in utero and -22% weight deviation at birth. Umbilical artery Doppler studies were not used.

In the ultrasound group 467 fetuses were thought to be SGA. Of these, 77 were actually SGA at birth while 390 were non-

SGA. 2689 fetuses were thought to be non-SGA. Of these 2670 were actually non-SGA at birth while 19

were SGA. For detection of SGA this gives

o Sensitivity 80%o Specificity 87% o PPV 16.5%

In the control group 217 fetuses were thought to be SGA. Of these, 44 were actually SGA at birth while 173 were non-

SGA. 2984 fetuses were thought to be non-SGA. Of these 2932 were actually non-SGA at birth while 52

were SGA. For detection of SGA this gives

o Sensitivity 46%o Specificity 94%o PPV 20%

They also looked at LGA which they defined as more than +10% growth deviation in utero and more +22% weight for gestational age at birth. The comparable results were

Ultrasound groupo Sensitivity 91% o Specificity 70%

Control groupo Sensitivity 36%o Specificity 90%

Compared to the control group, the study group had A significant increase in CS and IOL because of suspected SGA A significant decrease in CS and IOL because of suspected LGA (because this finding was reassuring

of fetal health) No difference in perinatal mortality and morbidity.

Overall, routine ultrasound at 33 weeks identified 41% (33 fetuses) more truly SGA cases than palpation but at the cost of an additional 7% of women (250 fetuses) being wrongly identified as SGA which were not SGA at birth. Weighing these up:

High sensitivity of SGA detection has the potential to avoid stillbirth and other morbidity by early delivery of fetuses at risk.

However, false positive SGA cases may be delivered late preterm / early term when this is not necessary and this may have long-term cognitive consequences (children born 34 – 37 weeks have poorer educational outcomes than those born later).

ConclusionIn this study performed two decades ago and without umbilical artery Doppler measurement, a routine 33 week scan gave significantly better detection of SGA than a scan performed only for clinical indication. However there was a considerable false positive rate and resultant low positive predictive value. If the study was done now, the false positive may be less. There is no doubt that a large prospective trial is needed to determine the optimal way to screen for fetal growth abnormality given the poor detection rates with palpation.

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13. PREGNANCY OUTCOME DIABETES/OBESITY – PRE-EXISTING DIABETES, HbA1c and FETAL/INFANT DEATH (JUNE 2014) Tennant PWG. Diabetologia 2014;57:285 - 294 In Newcastle, north England, data were obtained on singleton pregnancies progressing beyond 20 weeks over the period 1996-2008 to compare perinatal death rates in offspring of women with and without pre-existing diabetes. Congenital abnormality pregnancies were excluded.

Of nearly 400,000 births, nearly 1600 women had pre-existing diabetes a prevalence of 4 per 1000. 78% were Type 1, 22% were Type 2.

The results were The median HbA1c levels were 7.8% around conception and 6.7% in the third trimester. Fetal Death

o Prevalence was 4 x higher among women with pre-existing diabetes o Rate was the same in Type 1 and Type 2 diabetes (both about 3%)

Infant Deatho Prevalence was 2 x higher among diabeticso Rate was the same in Type 1 and Type 2 diabetes (about 0.6%)

The HbA1c level was significantly associated with stillbirth and infant death. A lack of pre-pregnancy folic acid was significantly associated with stillbirth and infant death.

ConclusionStillbirth is 4 x higher in diabetic women and infant death 2 x higher compared to those without diabetes. Type 1 and Type 2 diabetes have the same outcomes. The HbA1c level and lack of pre-pregnancy folic acid are significantly associated with stillbirth and infant death.

14. PREGNANCY OUTCOMES DIABETES/OBESITY – OBESITY ANTENATAL LIFESTYLE ADVICE (JUNE 2014) Dodd JM for LIMIT Trial. BMJ 2014;348:g1285. This Australian RCT (n > 1000 each group) recruited women between 10 – 20 weeks gestation who had Booking BMI > 25 (41% were BMI 25 - 30, 59% were BMI > 30) and randomised them to comprehensive information about weight gain, diet and exercise in pregnancy or to usual care.

The results were: Intervention Control Gestational weight gain average 9.4kg 9.4kg NS GWG > recommended 42% 42% NS GWG < recommended 25% 25% NS Birthweight ≥ 90th centile for age/sex 19% 21% NS Birthweight ≥ 4000g 15% 19% Sig

ConclusionDisappointingly, the intervention group did essentially no better than the control group but for a small reduction in birth weight > 4000g. However, in both groups the GWG, though greater than recommended by 2009 Institute of Medicine (9kg for BMI 25-30, 7kg BMI > 30) was less than is commonly seen suggesting that the control group knowing they were in a study, possibly paid more attention to weight gain than they may otherwise have done – GWG only 9.4kg, we often see 30 kg!

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15. PREGNANCY OUTCOME AFTER FERTILITY TREATMENT – DONOR OOCYTE CYCLES: TRENDS AND OUTCOMES USA. (APRIL 2014) Kawwass JF. JAMA 2013;310:2426-2434. In the USA, with respect to donor oocyte IVF

Donor oocyte cycles increased significantly between 2000 – 2010 from 11,000pa to over 18,000 pa. Mean donor age was 28yo. Mean recipient age was 41yo. The recipient age had no negative impact on good perinatal outcome. Good outcomes were more likely with embryo transfer on Day 5 compared to Day 3 The mean number of oocytes retrieved increased from 17 to 19 over the 10 years The percentage of cycles using frozen oocytes/embryos increased from 27% to 40% Single embryo transfer (recommended when donor is < 35yo) remained very low although it increased

from 0.8% in 2000 to 15% by 2010. The low SET rate twin pregnancy rate of 37%. (In a survey of USA fertility experts in 2010, only 34% discussed SET with their patients. The situation is very different in Australia where SET is the norm).

A single live birth > 37 weeks and > 2500g resulted from 28% of fresh cycles

ConclusionAs above

16. PREGNANCY OUTCOME AFTER FERTILITY TREATMENT – SINGLE EMBRYO TRANSFER WITH ANEUPLOIDY SCREENING. ‘BEST’ RCT. (JUNE 2014) Forman EJ. AmJOG 2014;210:157.e1-6. Nearly 50% of all USA babies born after IVF are multiple gestations mostly because more than one embryo is returned. Twin gestations are associated with 4 – 16 x increased risks of

Preterm birth, SGA, respiratory morbidity, jaundice and cerebral palsy in the children Preeclampsia, diabetes, caesarean birth in the mothers.

In many other parts of the world, including Australia, single embryo transfer (SET) is the norm with the goal of IVF being the achievement of a singleton term birth.

The reason IVF units in the USA put back more than one embryo is to increase the overall live birth rates and because a cycle of IVF costs up to $20,000. However, a number of studies have shown that, while a double embryo transfer (DET) results in higher live birth rates than a fresh SET cycle (42% v 27%) the addition of a frozen SET cycle (using an embryo left over from the initial cycle) results in a cumulative birth rate of nearly 40%. This is comparable to one DET cycle but with considerably less morbidity.

This current USA randomised controlled trial (RCT) provides a slightly different take on this approach and compares the outcomes of a euploid (blastocyst biopsied) SET (n = 89 patients) with a DET transfer of 2 untested embryos (n = 86 patients). One fresh and up to one frozen cycle were included.

The results were: Mean number of blastocysts suitable for transfer were 5 – 6 in each group In the SET group, blastocyst biopsy revealed aneuploidy in 31% of embryos The cumulative delivery rate after up to 1 frozen transfer was

o 69% for the euploid SET NSo 72% for the DET

Multiple births wereo 1.6% for euploid SET Sigo 47% for DET

Preterm birth waso 13% for euploid SET Sigo 29% for DET

Birth weight < 2500g waso 11% for euploid SET Sigo 33% for DET

NICU admissiono 11% for euploid SET Sig o 26% for DET

ConclusionA single embryo transfer (SET) fresh cycle plus up to one frozen cycle with pre-implantation genetic screening (PGS) has the same live born rate as DET without PGS with much lower rates of multiple pregnancy, preterm birth and low birth weight. Note that even though it is widely practised, there is still debate in IVF circles about the benefits and disadvantages of PGS . Older techniques of PGS were associated with poorer outcomes than simple morphological selection of the best looking embryos but newer techniques such as blastocyst biopsy may be superior and further studies are being undertaken.

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17. PREGNANCY OUTCOME – SEVERE PREECLAMPSIA: EXPECTANT MANAGEMENT REMOTE FROM TERM: A RCT (MARCH 2014) Vigil-De Gracia P. Am JOG 2013;209:425.e1-e8. Preeclampsia occurs in +/- 5% of pregnancies with severe early onset preeclampsia accounting for 25% of cases. This randomised multicentre clinical trial in Central and South America was undertaken to determine whether expectant management (EXM) of severe preeclampsia at 28 – 33 weeks results in better perinatal outcomes than prompt delivery (PD) after steroid administration.

The EXM group were delivered for specific fetal or maternal indications - uncontrolled maternal BP, maternal complications, fetal compromise, persistent symptoms or upon reaching 34 weeks. 25% reached 34 weeks with the rest of the EXM group delivered earlier for the other indications.

There were just over 130 patients in each group. The results were :

Prompt Delivery Expectant Pregnancy Prolongation 2 days 10 days Sig Perinatal Mortality 9.4% 8.7% NS Composite Neonatal Morb 56% 56% NS Birth Weight 1540g 1660g Sig SGA 9% 22% Sig Abruption 1.5% 8% Sig Maternal morbidity 14% 38% Sig

ConclusionSevere preeclampsia < 34 weeks is best managed by prompt delivery after corticosteroid administration.

18. PREGNANCY OUTCOME – PREECLAMPSIA RECOVERY SPEED WITH IMMEDIATE POSTPARTUM CURETTAGE OF UTERUS: A RCT (MARCH 2014) Ragab A. Arch Gynaecol Obstet 2013;288:1035-1038 On the basis that preeclampsia is at least partly an immune response to the trophoblast, this group from Egypt randomised women with severe preeclampsia to blunt curettage or no curettage immediately after delivery. The treatment group had 220 women (170 severe pre-eclampsia, 50 eclampsia) while the control group had 200 women (160 severe preeclampsia, 40 eclampsia). Mean GA at birth was 31 weeks in both groups, and CS about 60% in both.

The results were: Curettage No Curettage Time for MAP to fall to 105mmHg postpartum 40 h 86h Sig Eclampsia 2 patients 11 patients Sig Platelet count recovery Faster Creatinine recovery No difference

ConclusionImmediate postpartum curettage possibly aids faster recovery from preeclampsia and reduces maternal morbidity. Further large studies are needed.

19. PREGNANCY OUTCOME – PREECLAMPSIA RISK: ROLE OF PERSONAL AND FAMILY PREECLAMPSIA HISTORY (APRIL 2014) Boyd H. Am J Epid 2013;178:1611-1619. Using multiple linked Danish health registries, the role of previous preeclampsia and family history of preeclampsia in the development of preeclampsia in 1.4 million singleton live births during the period 1978 – 2008 was investigated.

The findings were: Previous preeclampsia increased the risk of preeclampsia occurring at the same gestation in the index

pregnancy : o Previous preeclampsia < 34 weeks 25x increaseo Previous preeclampsia 34-6 weeks 20x increaseo Previous preeclampsia > 36 weeks 10x increase

If the woman’s mother had suffered preeclampsia, the woman had a 2x increased risk If relatives on her father’s side had suffered preeclampsia, the woman had a small increased risk

ConclusionA woman’s personal history of preeclampsia is the biggest predictor of future preeclampsia, especially a history of early onset preeclampsia.

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20. CONGENITAL ABNORMALITY – BREECH PRESENTATION AT DELIVERY: A MARKER FOR CONGENITAL ABNORMALITY (MAY 2014) Mostello D. J Perinatol 2014;34:11 – 15. Although it has long been held that breech presentation at term is associated with an increase in anomalies there is, in fact, little research into the topic. This population-based retrospective cohort study from the USA investigated the rates of anomalies in singleton breech v singleton cephalic born after 24 weeks.

The results were Breech Anomaly Rate Cephalic Anomaly Rate Term 9.4% 4.6% Sig Preterm 20.1% 11.6% Sig Anomalies over-represented in breech births were CNS, cardiovascular and musculoskeletal. Oligo and poly hydramnios were also more common with breech births

ConclusionBreech presentation at both term and preterm is twice as likely to be associated with fetal structural abnormality as cephalic presentation.

21. CONGENITAL ABNORMALITY – ISOLATED SINGLE UMBILICAL ARTERY: FETAL GROWTH, ANEUPLOIDY, MORTALITY: SYSTEMATIC REVIEW AND META-ANALYSIS (APRIL 2014) Voskamp BJ. Ultrasound OG. 2013;42:622-628. We have looked at isolated single umbilical artery (SUA) in previous OGS reviews Sept 2010: Relative risk for other anomalies: Cardiac 20 x, Renal 3 x, IUGR 2 xDec 2010: SUA aneuploidy rates were 0% if no other anomaly, 4% if one other anomaly, 50% if multiple anomaly in a cohort where many had also undergone prior NT screening (Nicolaides).

Isolated SUA is thought to be due to secondary atrophy of one of the umbilical arteries such that the cord has one artery and one vein rather than two arteries and one vein. It is very common, occurring in 1% of fetuses (up to 5% of twins). Cardiac and renal anomalies should be sought but, having been excluded, the outcome is little different from babies with two umbilical arteries apart from a possible small increase in growth restriction. There is no increased risk of aneuploidy in the absence of other abnormalities.

This study is a review of the literature of outcomes of seemingly isolated SUA (iSUA) foetuses identified on ultrasound before 24 weeks. Studies were eligible if they contained more than 30 fetuses with apparently isolated SUA and presented outcomes for these fetuses in comparison to non-iSUA fetuses. 3 cohort and 4 case control studies met inclusion criteria for a total of nearly 1000 patients analysed.

Compared to non-iSUA fetuses, iSUA fetuses had SGA at birth OR 1.6 (0.97 – 2.6) NS (effect seen in the smaller studies only) Preterm birth < 37w OR 2.1 (1.4 – 3.2) Sig (?iatrogenic from too much monitoring) Preterm birth < 34w OR 3.3 (1.4 – 7.7) Sig PNMortality OR 2.0 (0.9 – 4.2) NS (effect seen in the smaller studies only) Aneuploidy 0.6% (4 cases – any comparison?)

The editor suggests that the preterm birth rate may possibly be iatrogenic, related to excessive fetal surveillance and monitoring. There was no significant increase in SGA or perinatal mortality with such increases seen only in the smaller studies, not the larger ones. ConclusionIsolated SUA is common and is not clearly associated with any adverse outcome although there is a trend toward impaired fetal growth and perinatal mortality. How to manage?

A single growth scan at 32 weeks may be appropriate (but is probably not necessary) CTGs should be reserved for those shown to be growth restricted. Pregnant women should be reassured that isolated SUA is unlikely to represent any adverse risk for

their pregnancy.

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22. CONGENITAL ABNORMALITY – MATERNAL REPORTING OF PRENATAL ULTRASOUND DEFECTS (MAY 2014) Weedn AE and USA National Birth Defects Prevention Study. Birth Defects Research (Part A) 2014;100:4 – 12. This USA National Birth Defects Prevention Study is an ongoing multisite population-based case-control series of studies implemented by the CDC in 1997. Its goal is to identify causes of anomalies by comparing pregnancy features in pregnancies with versus without anomalies.

This particular study’s focus is on the detection rate of anomalies prior to birth. It ascertains this rate by telephoning women who have given birth to a baby with one of 30 reportable anomalies and asking them if the anomaly was detected during pregnancy. The phone call takes place between 6 weeks to 2 years after birth.

The findings were: 46% of women reported that the anomaly had been detected before birth The best rates of detection, 73 – 83%, were for anencephaly, isolated omphalocoele, gastroschisis and

renal agenesis The worse rates of detection, 15 – 28%, were for isolated cleft palate, cleft lip with or without cleft

palate and limb deficiency Obese women were 20% less likely to have had the anomaly detected Hispanic women were 20% less likely to have had the anomaly detected

Possible reasons for the low rates of reporting that ultrasound detected the anomaly before birth are Detection of some anomalies is difficult The quality of ultrasound services is variable Some poor women eg some Hispanics, do not have a pregnancy ultrasound Some women do not recall or understand if they have been told the ultrasound is abnormal.

ConclusionThe antenatal diagnosis of fetal anomalies in the USA appears to be low at 45%.

23. ANTENATAL FETAL DIAGNOSIS – OBSTETRICIAN RECOMMENDATION FOR INVASIVE PRENATAL TESTING AND THE INFLUENCE OF THE ‘PRECIOUS BABY’ (MARCH 2014) Srebnik N. Hum Reprod. 2013;28:3007-3011. This study from psychologists in Israel quantitates what we all know – pregnancy care is affected by mode of conception, with IVF pregnancies being treated as more precious/vulnerable than spontaneously conceived pregnancies.

Two scenarios were presented to 163 Israeli obstetricians: Both involved a 37yo woman at 18 weeks with normal biochemical and ultrasound findings regarding

Down syndrome (low risk, < 1 in 380). The only difference was that one woman had conceived spontaneously and the other on the 4 th IVF

cycle after 3 years of infertility.

The obstetricians were asked whether they would recommend amniocentesis for Down syndrome testing. The results were:

Obstetricians advising amniocentesis To the woman who had conceived spontaneously 44% To the woman who had conceived after IVF and infertility 19% Sig

ConclusionObstetricians vary the advice they give to pregnant women regarding amniocentesis according to mode of conception. Whether or not they should is another question.

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24. ANTENATAL FETAL DIAGNOSIS –POTENTIAL DIAGNOSTIC CONSEQUENCES OF APPLYING NIPT IN A COUNTRY WITH EXISTING T1 SCREENING (JUNE 2014) Peterson OB, Hyett J and the Danish Fetal Medicine/Clinical Genetics Study Groups. Ultrasound OG 2014;43:265 – 271.

Free fetal DNA (cffDNA) in the maternal circulation, known as non-invasive pre-natal testing (NIPT) detects 99% of T21 and > 90% of T18, T13 and monosomy 45X0. However, currently it does not detect aneuploidies except numerical (but not structural) abnormalities of T21, T18, T13 and the sex chromosomes. It does not detect ‘atypical aneuploidies’ including deletions, duplications and translocations or aneuploidy those in autosomes other than 13, 18 and 21. These account for over 25% of all significant aneuploidies.

Researchers and public health experts in countries all around the world are trying to determine which combination of first trimester screening provides

Best detection rates for all significant aneuploidies (but especially those where the child will survive but have disability)

Lowest invasive testing / iatrogenic miscarriage rates Best cost-effectiveness

In Denmark, all women are routinely offered late first trimester combined nuchal translucency (NT) and PAPP-A/fbHCG (cNTS). This study re-analysed women who had been screened by cNTS to investigate how many aneuploidies would have been missed by moving to NIPT for all women rather than continuing with cNTS. The researchers made the mathematical assumption that the detection of T21, T18, T13 was 100% and instead focused on atypical aneuploidies.

Just under 200,000 pregnancies in Denmark had combined first trimester nuchal translucency screening. Of these, 10,000 (5%) were high risk for T21 (risk higher than 1:300). Karyotyping showed that 1100 (1 in 9) had an abnormal result. Of these abnormal results, 310 (27%) were atypical aneuploidies which would have been missed by NIPT. Most were phenotypically significant aneuploidies.

Trisomy 21 o cNTS detects over 90% of T21o NIPT detects 99% of T21, a significant improvement in T21 detection

Atypical aneuploidies (account for about 25% of significant aneuploidy)o NTS detects 33%.

Most atypical aneuploidies are not detected because they occur in women with a low risk for T21 (<1 in 300).

o NIPT detects nil atypical antibodies

In looking for the best detection / lowest invasive testing regimen, the authors (like others) suggest a possible sequential combination of tests that may offer the best detection with lowest invasive testing rates:

cNTS for all women, then :

High risk cNTS 1:100 or higher

OR any of

Maternal age ≥ 40years, NT thickness > 99th centile, PAPP-A < 0.2 MoM, fbHCG < 0.2 or ≥ 5 MoM

invasive testing (about 3% of women)

Intermediate risk, say 1:1000 and no maternal age, NT thickness, PAPP-A, fbHCG concerns:

NIPT (about 7% of women)

ConclusionThe search for the best approach - highest detection, lowest invasive testing/miscarriage, optimal cost-effectiveness - to antenatal aneuploidy detection continues.

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25. ANTENATAL FETAL DIAGNOSIS – CELL FREE DNA TESTING (NIPT): FALSE POSITIVE RESULTS (MARCH 2014) Mennuti MT, Dugoff L. AmJOG 2013;2009:415-419. Since 2011, testing of cell free fetal DNA in the maternal circulation has been commercially available, a technique known as non-invasive prenatal diagnosis (NIPT).

Using NIPT: The detection rate for Trisomy 21 is 99% while it is lower for Trisomy 18 and 13. The improved

performance for T21 is largely because T18 and T13 often have placental mosaicism leading to some false negative results. This is much less commonly the situation with T21.

False positive rates are about 0.5% for all three of these trisomies. However, with low prevalence conditions such as T18 and T13, false positives can actually be more common than true positives

In the study abstracted, 8 false positive results are reviewed (5 x T18, 3 x T13). All were confirmed as false positives on invasive testing.

Conclusion False negatives for T21 do occur but NIPT is the most accurate T21 test we have while, for T18 and

T13, it is not yet clear if NTS/ultrasound is superior to NIPT NIPT is not a diagnostic test. Confirmation of a positive result via invasive techniques is always

needed before TOP. After an NIPT positive result for T13 and T18, amniocentesis may be preferable to CVS given

placental mosaicism may be reflected in CVS results as well as NIPT

26. ANTENATAL FETAL DIAGNOSIS – NIPT DNA SEQUENCING versus STANDARD ANEUPLOIDY SCREENING (JUNE 2014) Bianchi DW for CARE Study Group. NEJM 2014;370:799-808. This small study, just over 2000 women in a general population, not a high risk population, compares free fetal DNA testing with ‘standard’ USA screening for T21, T18 and T13 which involves serum screening in the first or second trimesters (NT screening is little used in the USA because of the shortage and expense of sonographers). The primary aim was to compare the false positive rates.

There were 5 cases of T21, 2 cases of T18 and 1 case of T13. All were detected by both methods.

The results were NIPT ‘conventional’ serum testing T21 false positive 0.3% 3.6% Sig T21 positive predictive value 45% 4% Sig T18 false positive 0.2% 0.6% Sig T18 positive predictive value 40% 8% Sig T13 false positive 0.1% 0.5% NS

The false positive cases detected by the two methods did not overlap.

The editor criticised the study on the following grounds: The study is too small to compare detection rates for a rare condition such as aneuploidy while

comparing false positive rates without discussing detection rates is not scientifically valid A high percentage of DNA samples were collected in the third trimester when the amount of fetal DNA

in the maternal circulation is higher but the utility of aneuploidy detection is generally lower The ‘routine’ serology screening undergone by the women in the comparison group was actually not

very comprehensive, with only 3% having the integrated screening regimen which is associated with the lowest false positive rate

The cffDNA/NIPT test remains extremely expensive for an outcome as rare as aneuploidy (≤1%) in a general population

ConclusionCell free DNA Is a promising technology and no doubt the way of the future with respect to fetal aneuploidy detection. For now, however, it is too expensive and too limited in application (even in terms of aneuploidy detection) to be universally introduced. In addition, it does not detect major structural but non-aneuploid abnormalities which can be seen on the 12 week NT screening ultrasound.

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27. ANTENATAL FETAL DIAGNOSIS – NIPT CELL FREE DNA TESTING: FETAL SEX CHROMOSOME ANEUPLOIDY (MAY 2014) Nicolaides K. Fetal Diagn Ther 2014;35:1 – 6. Cell free fetal DNA (cffDNA) non-invasive pre-natal testing (NIPT) has been extended to assess sex chromosome aneuplodies as well as T21, T18 and T13.

To assess the accuracy of cffDNA/NIPT in the diagnosis of sex chromosome anomalies, maternal serum samples from pregnancies with known sex chromosome results were analysed using cffDNA.

The results were: 5 of the 177 samples did not yield results leaving 172 with results. 59 cases of 46 XX

o 57 identified correctly as 46 XX by cffDNA/NIPTo 1 identified incorrectly as 47 XXX (2% false positive)o 1 failed to provide a result

59 cases of 46 XYo 58 identified correctly as 46 XYo 1 failed to provide a result

59 cases of sex chromosome aneuploidieso 49 cases of 45 X0

43 identified correctly as 45 X0 (8.5% false negative) 3 misidentified as 46 XX 1 misidentified as 46 XY 2 failed to provide a result

o Other sex chromosome aneuploidies 5 cases of 47 XXX all correctly identified 3 cases of 47 XYY all correctly identified 1 case of 47 XXY correctly identified 1 case failed to provide a result

ConclusionNIPT is most accurate with respect to T21 detection – < 1% false negatives and false positives. Accuracy with respect to other aneuploidies is not quite as good. Consequently, as the panel of tests offered by NIPT expands, its overall accuracy diminishes

28. GENETICS AND ETHICS: 23andME AND THE FDA (JUNE 2014) Annas G, Elias S. NEJM 2014; 370:986 -988. Direct to consumer gene testing has been banned in Germany on the basis that risk (error, uncertain significance of results, need for GPs to spend hours counselling after such tests, need to spend large amounts of money to further investigate possible increased risks etc) exceeds benefit at the present time.

Such restrictions are not in place in most other countries and in August 2013, the genetic testing company 23andMe (CEO is the ex-wife of Sergei Brin so lots of Google money behind it) began an advertising campaign touting direct-to-consumer (DTC) testing kits using a saliva swab to identify genetic markers associated with 254 specific diseases and conditions. However, in November 2013, the USA Food and Drug Administration (FDA) ordered the company to stop marketing the kits because of 23andMe’s failure to confirm it had analytically and clinically validated the kits as safe and effective.

With 6 billion base pairs in the human genome, even an error rate of 1 per million DNA base pairs analysed would result in 6000 errors if the entire genome was analysed. While 23andMe does not offer whole genome analysis, instead offering a much more limited genome screen, it nevertheless needs to be able to demonstrate the accuracy of its testing to the FDA because it is a DTC product. In addition, as the Germans have declared, while the initial test is cheap the follow up is expensive in both time and further testing.

A key point in this matter is that, while DTC kits are currently under scrutiny, the accuracy of genetic tests iordered by a doctor (as opposed to DTC) receives essentially no oversight. Even the companies that perform testing for T21 using cell free fetal DNA in maternal blood are not required by the FDA to provide any validation of their test accuracy.

ConclusionAt the present time, genetic testing capability appears to have exceeded the ability of the law to regulate it.

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29. GENETICS AND ETHICS: PRE-NATAL WHOLE-GENOME SEQUENCING: IS THE QUEST TO KNOW A FETUS’S FUTURE ETHICAL? (APRIL 2014) Yurkiewicz IR. NEJM 2014;370:195 - 197In recent decades, prenatal diagnosis has been focused on the detection of common trisomies and other major anomalies, in order to allow selective termination of pregnancy.

Now we are in the genomic era where, for a few hundred dollars and a saliva sample, anyone can have their genome analysed and their health vulnerabilities identified. It is not surprising to learn that researchers have recently succeeded in sequencing the entire fetal genome from cell free DNA detected in the mother’s blood. Though this option won’t be widespread any time soon, extensive fetal genomic testing is already occurring.

Such extensive fetal DNA analysis capability raises major ethical questions regarding the right of the fetus/child to privacy and how that competes with the parents’ rights to reproductive choice.

Information parents may learn about their fetus from such antenatal testing includes Risks for childhood diseases Carrier status for recessive conditions The risk for complex adult-onset diseases The presence of genes causing adult-onset autosomal dominant diseases The likelihood of certain traits

The consequences of this may be Psychological burden of information on parents and children Damage to self-esteem of the parent or child Alteration of the family’s view of the child Stigmatisation of the child Discrimination against the child Increased rates of pregnancy termination

The American College of Medical Genetics / American Academy of Pediatrics recently stated that screening decisions should be made on the basis of the child’s best interest while a family benefit as the justification for genetic screening was more questionable.

However, many, including the authors of this article, disagree with that position, arguing that, after counselling, parents should be allowed access to as much genetic information about their child as they want. They argue that this opportunity is a basic right of reproductive choice and parental autonomy even if the parents then make a choice that is not in the best interests of the child. Alternatively, being forearmed with knowledge about the child may help parents prepare for the child’s future, they say.

ConclusionPrenatal whole genome sequencing of the fetus raises significant ethical issues around the rights of the fetus/child versus the rights of its parents.

30. TERATOGENESIS/FETAL HARM – SSRI AND RISK OF AUTISM (APRIL 2014)Hviid A. NEJM 2013;369:2406 – 2415 In the USA, SSRIs are used by more than 5% of pregnant women. Recent studies have suggested that the risk of autism is doubled by SSRI intake in pregnancy. However, it is very difficult to sort out causality from association as women on SSRIs have social circumstances and other drug/alcohol/tobacco intake that may be confounders. Depression itself may also be linked to autism.

This cohort study from Denmark looked at 650,000 births for the decade 1996 – 2005 inclusive and the SSRI prescriptions filled by their mothers before and during pregnancy (1% were on SSRI).

Compared to those not on SSRI, the risk of the child having autism spectrum disorder was: Autism RR

Took SSRI in first trimester 1.35 (0.97 – 1.87) NS Took SSRI during pregnancy but not before 1.40 (0.92 – 2.13) NS Took SSRI before pregnancy but not during 1.46 (1.17 – 1.81) SIG

ConclusionThe increased autism risk associated with SSRI use before but not during pregnancy suggests that the risk may possibly be due to the indications for the drugs rather than an effect of the drugs itself. Given the benefits and safety profile of SSRI in appropriately-selected patients, this study provides reassurance for women who are prescribed this class of medication in pregnancy.

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31. TERATOGENESIS/FETAL HARM – SSRI AND NEONATAL PERSISTENT PULMONARY HYPERTENSION: SYSTEMATIC REVIEW AND META-ANALYSIS (MAY 2014)Grigoriadis S. BMJ 2014;348:f6932. A possible association between SSRI use and the development of persistent pulmonary hypertension in the newborn (PPHN) was suggested in 2006. Subsequent data have been contradictory. From Canada, this meta-analysis and systematic review looked at all studies published until 2012 and found 5 cohort and 2 case-control studies which met critera for quantitative analysis.

The findings were SSRI use timing Odds Ratio for developing PPHN

Use for most or all pregnancy 3.3 (1.6 – 7.0) Sig Use in late pregnancy 2.5 (1.3 – 4.7) Sig Use at any time 1.6 (0.8 – 3.0) NS Use in early pregnancy 1.2 (0.6 – 2.6) NS

The absolute risk increase for developing PPHN after exposure to SSRIs in late pregnancy was 2.9 to 3.5 per 1000 infants (compared to baseline of 1 - 2 per 1000 infants). Because PPHN is rare, the authors calculated that 320 women would need to be treated with an SSRI in late pregnancy to result in a mean of 1 additional case of PPHN (NNH = 320).

ConclusionThere is a small increased risk of PPHN in neonates exposed to SSRI in utero in late pregnancy (NNH = 320). SSRIs should not be withheld when indicated but neonatologists must be informed when caring for babies whose mothers have taken such medications. SSRI use in early pregnancy was not associated with PPHN.

32. TERATOGENESIS/FETAL HARM – PERICONCEPTIONAL VITAMINS AND FETAL DEATH (JUNE 2014)Nohr EA. Int J Epidemiol 2014;43:174 – 184. Data from the Danish National Birth Cohort were used to examine the association between periconceptual multivitamin use versus folate only use versus no use with respect to risk for early and late fetal death.

The findings were 62% took multivitamins, 6% took folate only, 32% took neither during the periconception period (6

weeks before to 6 weeks after conception) Compared to non-users, periconception multivitamin use was associated with

o A significant increase in fetal death < 20 weeks HR = 1.2o A significant decrease in fetal death > 20 weeks HR = 0.8

Folate only users had no significant difference in outcomes from non-users

ConclusionIt is difficult to know both what to make of the findings of this retrospective study and how to construct a plausible biologic explanation for them. A large RCT is needed to investigate the issue further.

33. GENERAL: HOUSING AS HEALTHCARE: NEW YORK EXPERIMENT (APRIL 2014) Doran KM. NEJM 2013;369:2374-2377. Of the 34 countries in the Organisation for Economic Co-operation and Development (OECD), the USA ranks first in expenditure on health care and 25th in expenditure on social services. The latter is likely one reason why its health outcomes are so poor despite the billions spent. Estimates suggest good health is due to:

Genetics 30% Behaviour 30% Environment 30% Health Care 10%

Good health is unlikely if someone is homeless or unstably housed. At the same time, such groups are often high-cost health service users, part of the 5% of Medicaid (USA health care for the poor) recipients who account from 50% of Medicaid expenditure. This state government project from New York aims to use the provision of supportive housing (affordable housing plus supportive services) as a means to both reduce health expenditure and improve outcomes in this group. Preliminary findings have shown this to be the case.

ConclusionImproving social services such as housing appears to be an effective way to both reduce healthcare costs and improve outcomes.

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