Griff Jones, Darryl Maxwell (Division of Perinatology, Ottawa General Hospital and Fetal Medicine Unit Guy’s and St.Thomas’ Hospital, London)
Cervical Ultrasound in Pregnancy
Prog. Obstet & Gynaec, 14, p.80
The uterine cervix undergoes considerable physiological, biochemical and anatomical changes during the transition between the antenatal and intrapartum periods. Digital examination consistently underestimated length by more than 13mm. In contrast, ultrasonographic measurements correlated well with those obtained using a ruler on the postoperative specimen.
The average cervical length to be between 35-40mm. Up to 6mm dilatation at the internal os was normal with no significant cervical change seen from the 10th to the 36th week of gestation.
115 women with risk factors for cervical incompetence were studied. Patient management was largely based on clinical (as opposed to ultrasound) findings. Of the women with evidence of moderate cervical weakness on ultrasound, one-third were found to have clinically normal cervices. With expectant management, 75% delivered before 34 weeks’ gestation. Most of the remaining two-thirds, underwent cerclage with 25% delivering before 34 weeks.
Riley et al report a 50% risk of preterm birth in women co-incidentally found to have cervical shortening and membrane funneling on transabdominal scanning.
Brown et al suggest that adequate cervical images were more likely to be obtained by transvaginal scanning than by transabdominal U.S.G. The cervix could be visualized transvaginally 99% of the time. When transabdominal and transvaginal cervical length measurements from the same woman were compared, transabdominal measurements were on average 5mm longer, presumably secondary to bladder filling. Of the 30 women, 29 demonstrated an increase in cervical length with increasing bladder volume. Confino et al also reported cases in which quantified bladder filling or manual pressure exerted via the transducer led to significant reductions in internal os dilatation in patients with suspected incompetence.
Digital examination only assesses that portion of the cervix below the vaginal wall. Goldberg et al found the mean cervical lengths in 43 pregnant women measured by transvaginal ultrasound (39mm) to be over twice as long as those measured digitally (19mm) by experienced examiners. Similarly, Sonek et al found that digital measurement of cervical length showed a poor correlation with vaginal ultrasonography.
Safety and acceptability:
Heath et al questioned 100 consecutive women about the acceptability of a transvaginal scan at 23 weeks gestation: 94% experienced no, or minimal, discomfort only and 98% reported no or only mild embarrassment. Half of the women found it to be less uncomfortable than a speculum examination.
Normal values for cervical length
There appears to be no clinically significnat difference between the mean cervical lengths of primiparous and multiparous women.
It is possible that ethnic differences in cervical length exist. The work of National Institute of Child Health and Human Development Maternal-Fetal Medicine Unit Network has shown a short cervix (£ 25mm) to be significantly more common in high risk women.
Murakawa et al studied 32 women presenting with threatened preterm labour. None of the 15 women with cervical lengths greater than 30 mm delivered preterm. If the cervix was less than 30mm, 65% delivered preterm and all early births were identified. All women with a cervical length below 20mm delivered preterm.
Gomez et al developed the term cervical index to include information about endocervical length and funnel length in a single figure. Funneling was present in 58% of women and associated with a nearly 3-fold increase in the risk of preterm birth. A complex statistical analysis suggested that a cervical index ³0.52, cervical length < 18mm, funnel length > 9mm and funnel width > 6mm were all significantly associated with preterm birth. All the patients who delivered preterm had a funnel present.
The ability to diagnose (or exclude) placenta praevia is one of the main benefits ascribed to antenatal ultrasound. Provided that the placental edge is at least 20mm from the internal os, a vaginal birth appears safe.
Cervical conization may iatrogenically predispose to cervical incompetence.
Assessment of risk of preterm birth
3000 women of mixed-risk were screened at both 24 and 28 weeks of gestation. The mean cervical length was approximately 35mm and the overall incidence of spontaneous preterm birth £ 35 weeks’ gestation was 4.3%. There was a clear inverse relationship between cervical length and risk of preterm birth. A short cervix (£ 25mm) was associated with an 8% probability of spontaneous preterm delivery £ 35 weeks gestation in low-risk parous women. In high-risk women, this probability climbed to 31% with the same cervical measurement.
The second study was carried out at a single inner city centre in the UK. Results from cervical scans at 23 weeks’ gestation were blinded unless the length was less than 16mm. A cervical length of £ 15mm at 23 weeks’ gestation carried a risk of spontaneous delivery £ 32 weeks of 50% and correctly identified 58% of these births.
The third study was from a well-defined geographical area in Helsinki, Findland with a 99% white population. The mean cervical length was just over 40mm and a short cervix was defined as one £ 29mm, corresponding to the 3rd centile.
All three studies confirm the ability of transvaginal cervical ultrasound to reliably stratify women by risk of spontaneous preterm birth. Even more importantly, the background or pre-test risk of spontaneous preterm birth must be taken into account when interpreting cervical sonograms.
If the funnel length was greater than the length of closed cervix below it, 75% of patients delivered before 37 weeks’ gestation. A funnel width exceeding 15mm was another risk factor. Heath et al found that all women with a cervical length £ 15mm exhibited funneling compared to only one-third of those with a cervical length of 16-25mm.
Sonek subsequently reported the same phenomenon in women not believed to have cervical incompetence, using transvaginal scanning. He stated that the funneling could be accentuated or brought on by gentle manual pressure on the uterine fundus and advocated this as an ‘internal os stress test’.
At present, transfundal pressure cannot be standardised. More recently, reports have appeared advocating the use of a postural challenge, with the cervix being scanned first while the mother is supine and then when upright.
The final report of the MRC/RCOG Multicentre Randomised Trial of Cervical Cerclage suggested benefit in only 4% of cases with prior clinical uncertainty. Detailed inspection revealed that cerclage improved outcome only after three or more previous very early deliveries. The mean interval between cerclage removal and delivery was 2.3 weeks.
Both Andersen et al and Quinn reported all the McDonald sutures in their series to be in the middle third of the cervix. The optimal placement of a suture was obtained in the single patient that was treated with a Shirodkar-type cerclage, involving preliminary dissection of the anterior vaginal wall.
Post cerclage follow up
Between 25-30% of patients developed funneling above the cerclage.
Goldenberg et al scanned 147 twin pregnancies at 24 and 28 weeks’ gestation. A cervical length of less than 25mm was twice as common in twin pregnancies as in singletons and became more common as gestation advanced, occurring in 18% of women at 24 weeks and 33% at 28 weeks.
Cervical ultrasound and routine antenatal care
Although Zalar suggested that knowledge of transvaginal cervical ultrasound measurements can lead to a reduction in spontaneous low birth-weight deliveries, it cannot yet be concluded that cervical ultrasound has a place in routine antenatal care in low-risk pregnancies.
Preterm prelabour rupture of the membranes
The authors were unable to demonstrate a significant relationship between cervical length and the number of days to spontaneous labour.
TECHNIQUES FOR CERVICAL SCANNING
Cervical images are best obtained transabdominally with a full bladder. Unfortunately, this is associated with artificial lengthening of the cervix and potential closure of a dilated internal os. Therefore, it will lead to false reassurance in some cases. The external os can also be difficult to identify transabdominally. In the studies of Varma et al, an inflated Foley catheter balloon was placed against it to overcome this problem.
This remains the gold standard for cervical imaging. Sonek et al have advocated the use of a probe with a 240° scanning field, this would appear to be unnecessary. Pressure on the cervix can falsely increase the measured length and obscure funneling at the internal os. Failing to appreciate that not all cervical canals follow a straight line can lead to underestimates of length. At least 3 measurements should be taken and the shortest (not the average) used. Most authors advise scanning over approximately 5 min to detect dynamic changes. The presence of a funnel should be noted and funnel width and length recorded. Some authors have reserved the term ‘funnel’ for membrane protrusions greater than 5mm down the endocervical canal, referring to anything less as ‘nippling’.
A glove-covered 3.5MHz or 5 MHz sector or curvilinear transducer is applied to the perineum to visualize the cervix. It is reportedly easily tolerated by patients, but is best performed before digital or speculum examination which, by introducing air into the vagina, produce artefact. The technique has been particularly useful in cases of prolapsing membranes when cerclage is not being undertaken. The contrast provided by the funnel or membranes usually allows excellent visualization and serial monitoring. Transperineal ultrasonography may prove to be an acceptable mass screening technique.
As proposed by Iams et al, ultrasound imaging suggests cervical competence to be a continuous variable. Infection has attracted considerable interest as one of the most important aetiologies behind preterm labour and delivery. A weak or short cervix could offer less resistance to ascending infection. Half have positive amniotic fluid cultures.
Iams et al have recently reported that a cervical length of less than 25mm at 24 weeks’ gestation is strongly associated with subsequent perinatal infection. Bacteria can ascend the genital tract attached to motile sperm. Antibiotics may play just as important a role as cervical cerclage in preventing prematurity. As prostaglandins are implicated in the process of cervical ripening, non-steroidal anti-inflammatories such as indomethacin may have role for ultrasonographic cervical change, at least before 28 weeks’ gestation. Cervical ultrasound undoubtedly allows a far better assessment of risk than clinical examination.
Frank Johnstone (Department of Obstetrics and Gynaecology, University of Edinburgh UK)
Drug Use in Pregnancy
Progress in Obstetric and Gynaecology vol.14
This article is about a broad range of drugs which have some psycho-active properties and which are used for non-therapeutic reasons in pregnancy.
All the drugs (with the possible exception of benzodiazepines) appear to have a common final pathway. They all act by increasing dopamine release. But for all of them, the common end-point where dopamine is released forms part of a circuit known as the brain reward system, consisting of a small group of nerve cells extending from the ventral tegmental area of the midbrain to limbic areas such as the nucleus accumbens, with projections to the pre-frontal cortex. The markedly reduced activity in the brain reward circuits on withdrawal also explains dependence.
Over the past few decades, use has spread to most countries of the world. This is due partly to a general increase in use of psycho-active drugs, improvements in communication and transportation and the globalisation of the world economy. Indeed, tobacco companies have used international trade agreements to open up markets in the developing world, and the same factors facilitating trade in legal goods also facilitate trade in illicit drugs.
Many women, who do not acknowledge any problem with their drug pattern, may present for the first time to the health care system because of the pregnancy. This presents a window of opportunity for harm minimisation and education. Pregnancy can be a great motivator. Drug use in pregnancy is already known to be a major public health problem.
Some Effects of Drugs on Pregnancy
Effects in animal studies (often with high doses) may be due to maternal toxicity rather than direct effects on the fetus (e.g. drug induced anorexia). There may be selection bias based on obvious chaotic drug use, so that the women studies are quite unrepresentative of population use. The small numbers studied may be inadequate to study infrequent events. Because of editorial and reviewer bias there may be preferential publication of studies which report harmful effects. Many drug users are polydrug users and this makes it difficult to isolate the effect of one drug. There are major problems in separating the effects of drug use from the other adverse personal, psychological and social circumstances in which drug use is taking place.
Injecting street heroin is dangerous and in most cohorts of users the mortality is at least 1% each year. The commonest cause of death is respiratory depression due to overdose. The other major medical complications relate largely to non-sterile injecting, resulting in transmission of hepatitis B, and most importantly hepatitis C and HIV.
There is no convincing evidence that opioids cause fetal abnormalities.They probably have a small inhibiting effect on fetal growth, though this is less than the effects of smoking. In all large studies, there is a modest increase in perinatal mortality due to preterm delivery and late pregnancy stillbirth, but it is uncertain how much of this drug is a drug effect rather than due to the effect of other variables. Preterm labour does seem to be more common in women injecting drugs rather than taking orally, possibly related to a higher risk of alternation between intoxication and withdrawal with relatively short acting injected drugs. An increase in meconium staining of the liquor is also consistently reported, related to episodes of fetal drug withdrawal.
There is a high rate of neonatal abstinence syndrome (NAS), ranging from 50-90% in women taking opiates daily. Symptoms may last for weeks or even months in a mild form. Typically, babies feed poorly and have tremor on handling, a shrill cry, sneeze and may have watery stools. Untreated, they can develop projectile vomiting and electrolyte disturbance, seizures and coma.
The largest study of 1760 cases of sudden infant death syndrome, showed a 7 times increased risk with maternal methadone use and a 5 times increased risk with heroin use.
Drug effects, and the consequences of an unstable, impoverished environment, are very difficult to disentangle, but this remains an area of concern.
As well as its central action, this drug has important peripheral effects on inhibition of re-uptake of noradrenaline in presynaptic nerve terminals. Catecholamines diffuse from the nerve terminals and the resulting high vascular levels cause vasoconstriction, tachycardia, hypertension and perhaps uterine contractility.
The vasoconstrictive properties of cocaine raise the possibility that there might be fetal damage during episodes of fetal ischaemia or subsequent reperfusion. However, the overall population risk for users does not seem very high, perhaps because only those with high dosage at key gestations are vulnerable. A large number of studies in women are consistent in reporting a decrease in birth weight. Preterm delivery is common and, although it is very difficult to adjust for multiple co-variates this is probably also a direct drug effect.
Of the 4000 compounds in tobacco smoke, there is good evidence that nicotine is the key drug of addiction and nicotine, carbon monoxide and cyanide are thought to have the greatest adverse effect on the fetus. World-wide, this is the most harmful drug for pregnancy.
There are well documented increased risks of spontaneous abortion, ectopic pregnancy, placenta praevia, placental abruption, preterm premature rupture of the membranes and preterm delivery. Birth weight is depressed by about 250g, with an increased risk of significant intra-uterine growth restriction. Intrauterine death in late pregnancy is more common. Overall, at least in the US, smoking causes an estimated 20-30% of the low birth weight rate and 10% of fetal and infant mortality. Postnatally, maternal milk production is reduced by about 30%. There are strong relationships with sudden infant death syndrome; respiratory disease and hospital admission in the first year of life; and an ongoing effect on respiratory disease in childhood. There are small effects on physical, mental and behavioural development of the child, of uncertain clinical significance.
There may be other long-term complications. Potentially carcinogenic tobacco metabolites are present in the first urine of babies whose mothers smoked in pregnancy. The babies of women who smoke were found to have a much higher frequency of a genomic deletion event that is commonly found in leukaemia and lymphomas of early childhood.
Diazepam overdose in 25 pregnancies was not accompanied by obvious fetal problems. Withdrawal may occur in the neonate, typically with irritability and slowness to feed and respond. There may be ‘floppy infant syndrome’ with poor suck, feeble cry, hypotonia, and sometimes poor temperature control.
Most studies have not reported an association between prenatal marijuana exposure and morphological abnormalities of the baby.
Data currently available do not allow any accurate estimate of risk.
The most widely used drugs at present are amphetamine analogues. Ecstasy (3,4 methylenedioxymethyl amphetamine, MDMA) is one derivative related chemically to both amphetamines and hallucinogens.
This is the only one of these drugs which is proven to be teratogenic. Fetal alcohol syndrome (FAS) has been reviewed in a previous issue of this series. A wide range of other alcohol-related birth defects appear to occur with heavy drinking. These adverse effects have been well documented with very high maternal intakes. Judging by animal experiments, alcohol may affect fetal brain development at any gestation. Threshold effects on subsequent reading, spelling and arithmetic abilities in children have been reported at low intakes.
The commonest substance is cigarette lighter refills (butane) but a wide range of products are used.
OPTIONS FOR DRUG MANAGEMENT
Many women who are not truly dependent on their drug will stop spontaneously as soon as they know they are pregnant. This applies to 15-20% of women who smoke, to many women who use ecstasy or cannabis episodically and it is also true of some controlled users of opiates.
It is said that most girls who smoke 3 cigarettes as adolescents will become dependent, with an average duration of dependence of 40 years. Sadly, having been recruited in adolescence, half of all smokers die because of the habit, one-third of them before the age of 65 years. 20% of all deaths in developed countries are caused by smoking: an enormous human cost which can be completely avoided.
Therefore, antenatal care should include advice to stop smoking, with easy access to programmes to support those who choose this. Brief intervention by family doctors is effective. Cutting down is probably not a useful aim.
Trying to persuade the woman to stop drugs may simply alienate her, lead to return to a more chaotic drug use pattern, and result in non-attendance for antenatal care. Therefore, the different options of detoxification, substitution and maintenance and other aspects of damage limitation need to be considered with full understanding of the woman’s aspirations and particular social and psychological circumstances.
For most women who are dependent and who have a long-standing opiate habit, substitution and maintenance is usually the preferred option. The drug of choice is methadone linctus. Methadone maintenance treatment has been extensively researched, and has been shown to be effective. Substitution should be prescribed as part of a package including social and psychological support.
Acute detoxification in pregnancy is not often appropriate but should be an option. The risks of withdrawal have probably been exaggerated in the past, and can be minimised by appropriate drug therapy to the mother. Detoxification can be carried out in the mid-trimester quite safely and this has a place in overall management.
Slow reduction may be preferred by some women for opiates, and is necessary for benzodiazepines.
Much of the management of drug misuse is damage limitation rather than cure, and in patients who continue to inject, it is essential to ensure that they have access to clean equipment, by needle exchange.
Maternity Care in Drug Users
Another important obligation on community care staff is effective liaison and communication with other agencies. Nothing is so guaranteed to reduce confidence as different agencies giving out different messages.
The opiate using woman should be warned that neonatal abstinence syndrome may occur, that her dose is not a reliable predictor, that it can present after several days and can last for weeks. She needs also to know that NAS is usually easily manageable.
Repeated non-sterile injection over years destroys peripheral veins, often leaving track marks (thrombosed, fibrosed veins). Occasionally there may be concern about the ability of the woman to look after her child. Many women worry that their baby may be taken away into care purely because they use drugs.
Occasionally, there maybe incidents involving violence or the threat of violence, most often caused by the partner or visiting friends in hospital.
Adequate pain relief can be obtained with opiates although much more frequent injections are likely to be needed. Because of the high fear about pain which many drug users have, epidural anaesthesia may be very useful.
Naloxone must not be used to reverse opioid induced respiratory depression in the newborn because of the risk of precipitating an acute opiate withdrawal crisis.
After delivery, a chart scoring for neonatal abstinence syndrome is helpful for all concerned. This is, of course, only one aspect of assessment. Withdrawing babies can usually be treated without drug management, with lots of cuddling, small frequent feeds, and patience. Babies may need neonatal unit care to maintain hydration and may need sedation. The logical drug is simply replacement of opiate, and neonatal morphine solution can be used.
Alessandro Ghidini, Nicola Strobelt, Anna Locatelli, Eloisa Mariani, Maria Giovanna Piccoli, and Patrizia Vergani
Isolated Fetal Choroid Plexus Cysts : Role of Ultrasonography in Establishment of the Risk of Trisomy 18
Am J. Obstet Gynecol April 2000, Volume 182, Number 4, Pgs. 972-977
Objective – The significance of isolated choroid plexus cysts found by ultrasonographic scan during the second trimester as a marker for trisomy 18 is
still debated. We analyzed our data and reviewed the series published in the English-language literature to calculate the likelihood ratio of trisomy 18 in the presence of isolated choroid plexus cysts; that is, the factor by which the individual risk of trisomy 18 is increased in the presence of isolated choroid plexus cysts.
Study Design – Likelihood ratios were calculated as ratio of the sensitivity to the faise-positive rate. Sensitivity was defined as the rate of isolated choroid plexus cysts detected at midgestation among fetuses with trisomy 18. False-positive rate was defined as the rate of choroid plexus cysts detected at midgestation in the population without trisomy 18. The sensitivities of all published series reporting rates of choroid plexus with trisomy 18 and in low-risk populations were included in the analysis. To these we added all cases of trisomy 18 diagnosed at our institution during the period January 1, 1988, through June 30, 1998, in which prenatal ultrasonographic examination was performed between 14 and 24 weeks’ gestation.
Results – The prevalence of second-trimester ultrasonographic detection of isolated choroid plexus cysts among fetuses with trisomy 18 was 6.7% [ 13/194]. Whereas that in the population without trisomy 18 was 0.9% [752/79, 583]. The likelihood ratio associated with isolated choroid plexus cysts was therefore 7.09 [95% confidence interval, 3.97 -12.18]
Conclusion – The presence of isolated second-trimester choroid plexus cysts increases the base risk of trisomy 18 by a factor of 7.09. This likelihood ratio can be multiplied by the risk calculated according to maternal age to obtain the individual risk of trisomy 18 and thus permit more accurate counseling of the patient.
Karim D. Kalache, Roland Wauer, Harald Mau, Rabih Chaoui, and Rainer Bollmann
Prognostic Significance of the Pouch Sign in Fetuses with Prenatally Diagnosed Esophageal Atresia
Am J. Obstet Gynecol April 2000, Volume 182, Number 4, Pgs. 978-981
Objective – Esophageal atresia may be diagnosed prenatally by ultrasonographic visualization of the blind-ending esophagus during fetal swallowing, which is referred to as the pouch sign. Our purpose was to determine whether this sign can be used to predict outcomes of affected fetuses.
Study Design – Four cases of esophageal atresia diagnosed in our center during the past 2 years were analyzed, in conjunction with 3 cases from published series. Ultrasonographic features of the pouch sign were categorized according to localization.
Results – In the neck pouch group [ n=3] 1 fetus died in utero and 1 died before a corrective operation could be undertaken. In the only fetus of this group to survive a staged repair was necessary because of a long atretic gap. Conversely, 3 of the 4 fetuses with a mediastinal pouch survived after a successful corrective operation, and primary repair was possible in all cases.
Conclusions – The base of the proximal blind-ending esophagus can be clearly localized by means of ultrasonography. Our data suggest that a neck pouch may be associated with an adverse outcome. This information may be useful in counseling parents when esphageal atresia is diagnosed prenatally.