Sara Paterson- Brown
Elective Caesarean Section – A Woman’s Right to Choose?
Progress in Obstetrics and Gynaecology-14, Year-2000, Pg.202
Traditionally, caesarean sections [CS] have been reserved for those situations where labour or vaginal delivery have been considered dangerous to either mother or baby and high rates of caesarean sections are met with knee-jerk reactions of disapproval. There is no evidence to support any specific target rate, however, and the recent drive in America to reduce the caesarean sections rate to 15% by the year 2000 have been criticized as causing increased maternal and fetal damage.
Although caserean section is becoming increasingly safe and evidence is mounting regarding risks of labour and vaginal delivery, there is no doubt that the evidence, as it stands, remains grossly incomplete. Despite this, the balance of acceptability between abdominal and vaginal delivery is changing. Whether maternal choice should be added to this equation when deciding how to deliver a woman is the subject of this review.
Ethics of Choice
Patient’s right to refuse or limit treatment is well tested and universally acknowledged, but the opposite right to request certain interventions, while perfectly acceptable in many situations, seems to have caused significant controversy when relating to caesarean sections.
Examples of Choice in Obstetrics and Gynaecology
Patients assert positive rights when requesting definitive treatment for unpleasant, but not dangerous, conditions: such as menorrhagia or urinary incontinence and even sterilisation to save themselves the daily inconveniences of contraception. How can we discredit ‘positive right’ in the context of patient choice for caesarean sections when we live with it in so many other professional situations?
Current Guidance on Choice
In UK, clinical governance is going to become a part of everyday life, and the booklet brought out by the General Medical Council on good medical practice guides us to patient choice quite deliberately: ‘patients want to be sure that their doctors respect their views and wishes when treating them’, and medical and clinical teams must have a positive attitude to patients and listen to their wishes and needs.
Balance of the Risks
It is interesting to reflect on an obstetric situation where there is patient and/or obstetrician anxiety: a woman with an uncomplicated pregnancy of a well-grown singleton fetus at term who has had a previous obstetric catastrophe of non-recurring cause, or previous numerous first trimester miscarriages, or prolonged infertility treatment. A perfectly common and acceptable course of action in these scenarios is for her to be delivered by electives CS at term. If we believe this is truly the safest way to deliver these ‘precious’ pregnancies, why do we not afford all mothers and babies similar concern?
To take argument further, we must explore the risks to infant and mother of elective CS versus labour [ labour as opposed to vaginal delivery or normal delivery must be used as the comparator, as no woman entering labour can be guaranteed a particular type of delivery].
Risks of awaiting Spontaneous Labour:
Unexpected antepartum stillbirth, although tragic, is not uncommon and increases 8-fold from 0.7 per 1000 on-going pregnancies at 37 weeks to 5.8 per 1000 ongoing pregnancies at > 43 weeks. If the risk of death increases as gestation advances from 37 weeks, what other lesser damage is occurring silently? We believe that less than 10% of cases of cerebral palsy are attributable to intrapartum insult and most are accounted for by antenatal events – we do not know what proportion of these occur at term. If subtle changes are effecting death, it is not unreasonable to suppose that lesser insults could effect damage at this time. This problem requires much more attention and research, but at present is a significant factor to remember when balancing elective delivery at 39 weeks against awaiting indefinitely for spontaneous labour to ensue.
Risks of Labour
Neonatal encephalopathy occurs at a rate of about 1 in 260 term babies of which 15% are directly attributable to intrapartum events, i.e. 1 in 1750 labours. Ingemarson et al conducted a 4-year follow-up on 102 babies born with an umbilical cord gas pH of less than 7.05 and compared them with 100
Controls and found significant speech deficits in those infants who had been acidemic at birth [19 of 102 compared to 8 of 100, respectively, [P= 0.03].
Risks of Vaginal Delivery
During vaginal delivery, the baby may sustain birth trauma in different ways and the problem is that, by definition, such damage is unexpected. Even when considering shoulder dystocia, most cases occur in babies not deemed to be macrosomic before [or even after] delivery. Instrumentation may be needed with risks of laceration or nerve palsies from the use of forceps, or of cephalohaematoma or retinal hemorrhages from ventouse extraction. Quantifying these complications is complex, as it depends on the obstetric population and the intrapartum care provided, but is not insignificant.
Risks of Elective Caesarean Sections
Electively delivering a baby abdominally pre-empts spontaneous labour reflective of fetal maturity and also deprives it of this physiological [if sometimes dangerous] stress: hence, such babies may be disadvantaged. There is good evidence demonstrating that, in the immediate postnatal period, respiratory function is more likely to be compromised in infants delivered by elective caesarean sections. In practical terms this risk can be minimised by delaying elective delivery until 39 completed weeks gestation, where the combined risk of transient tachypnoea and respiratory distress syndrome occurs in 1.8% of infants.
There is a complete lack of evidence concerning bonding and breast feeding in mother-baby pairs where the caesarean section was requested in the absence of pathology.
Long-term Fetal Effects from Different Modes of Delivery
Clearly, further work needs to be done in this area.
All caesarean sections, whether elective or emergency, prelabour or intrapartum, are usually grouped together, and have been performed for clinical reasons including maternal disease, rather than for maternal choice in otherwise healthy individuals. It is, therefore, hardly surprising that mortality, morbidity and satisfaction are worse in the caesarean section groups.
Evidence available from South Africa is that those women who require a caesarean sections are more likely to die than those women who achieve a successful vaginal delivery. The ratio of risk corrected for the reasons for the caesarean sections are approximately 5:1 CS versus vaginal delivery, and 1.5:1 for emergency intrapartum versus elective CS. This is obviously a hugely important area.
This is supported by the observation that there has yet to be a death reported in the UK of a previously fit woman who has undergone an elective CS under epidural anaesthetic with thromboprophylaxis and antibiotic cover.
In Massachusetts, a study looking at 2,803596 live-births from 1954-1985 found that, although the caesarean section rate quadrupled, the maternal mortality rate remained constant. The maternal death rate directly attributable to these clinically indicated CS was 5.8 per 100,000 CS deliveries, while the total death rate in women delivered vaginally was 10.8 per 100,000 vaginal deliveries. This puts death rates more into perspective, but with such low death rates in those countries not only able to provide safe conditions for CS but also able to audit them, it will take some time before this risk is fully appreciated in those few otherwise fit women who have a CS purely for maternal choice.
The results of many of these trials are conflicting, but the most recent and largest studies demonstrate that elective cesarean section appears safer than trial of scar or trial of breech delivery.
Short-term risks relative to mode of delivery
Short-term morbidity after elective caesarean section has been quantified by Obwegeser et al as 2% urinary infections, 1% wound infection and 12% maternal anaemia in a group of 108 women undergoing elective caesarean section for breech presentation. More recently, elective CS and vaginal delivery both had maternal morbidity rates of less than 2% while in those having emergency CS, rates approached 3%.
It is commonly believed that the general recovery after CS is slower than after vaginal delivery, but recent evidence from Scotland shows that instrumental vaginal delivery causes significantly more maternal morbidity than either CS or normal vaginal delivery.
The more we use regional analgesics for pain relief in labour the higher the instrumental vaginal delivery rate will be, and the real problem we have is that our social habits make this increasingly likely: how can we expect women to tolerate the severe pains of labour when our normal everyday habits are to avoid pain whenever possible.
Future obstetric performance after CS
The fact remains that, in the follow-up studies available, there are significant risks associated with future fertility.
The incidence of placenta praevia and placenta accreta increase almost linearly after each previous CS and placental abruption is increased by 2-4 fold. As the risk of these complications increases the more children a women has, her future reproductive intention is very relevant to any individual woman’s caesarean threshold.
Although all women entering labour face the risks of emergency CS, instrumental vaginal delivery and perineal trauma, the majority will achieve a normal vaginal delivery giving them an enormous sense of achievement and fulfillment. Whatever the outcome, however, the pain experienced – which can be combined with overwhelming fear and a feeling of loss of control – can have profound effects on the woman both short and long-term. This can have tremendous implications for the woman’s future and especially on sexual relations and childbearing. The evidence available to suggest CS is traumatic does not relate to those done for choice where we have no evidence either way.
Long-term problems from vaginal delivery
The anal sphincter is ruptured in 35% of women with their first vaginal delivery. Only a few of these are diagnosed clinically and, of those recognized and repaired, 85% will still have a defect at follow-up, with 50% being symptomatic. One of the problems with anal incontinence is the embarrassment women feel and, therefore, this condition is very under-reported. Urinary incontinence occurs in up to a third of women after vaginal delivery and 11% life-time risk of requiring surgery for either urinary incontinence or prolapse.
Thromboprophylaxis, antibiotics, regional blockade and early mobilization should already be standard practice, but we need to work more on surgical techniques to establish the optimum uterine closure, to reduce the likelihood of future placentation complications.
Despite the fact that active management of labour has yet to be proved effective in any randomised trial, there can be no doubt of the value of intensive one-to-one care of women appropriately prepared antenatally. How valuable early amniotomy is will remain debatable, but the process of accurate diagnosis of labour is something that few units can boast of or adult. Let us not forget that 45% of the intrapartum deaths investigated by CESDI had suboptimal antepartum care.
As doctors we must do no harm, yet this does not mean doing nothing, and it remains that the pregnant woman needs to be delivered either vaginally or abdominally. CS us a surgical procedure and, as such, could be considered ‘unnatural’. Hence, the human has a large brain with which to think and a narrow pelvis with which to move. Natural selection is taking us towards more difficult childbirth which we are intelligent enough to overcome.
Not Feasible Logistically
This is not proved. On first impressions, one may think that performing CS for choice would increase the work-load significantly, but the demand is likely to be very small. Midwives are in very short supply in the UK, which is sadly something that is unlikely to improve in the short-term and, therefore, planned delivery and maximizing health care assistant roles in the postnatal period could be seen as more efficient, cost effective and also ;potentially achievable.
THE LIKELY DEMAND
Obstetricians are clearly exposed to the worst of the obstetric scenarios and, therefore, it is perhaps not surprising that, when London obstetricians were questioned about their preferences in the hypothetical situation of being at term with uncomplicated singleton cephalic fetus, a not insignificant minority [17%] would opt for CS for themselves or their partner. The noteworthy feature of the al-Mufti study is not as much the overall CS preference rate but the female to male differences; 31% of females as opposed to 8% of males would choose an elective abdominal delivery in a completely uncomplicated pregnancy of a singleton cephalic fetus at term. This difference in choice between men and women cannot be because of professional exposure on the labour ward. What then? Is it that women are more likely to describe their embarrassing symptoms to the female gynecologists or are the latter just more sympathetic to them?
We know that in Italy, where obstetricians are obliged to do what their patients request, 4% of women choose CS. We do not have comparable figures from the UK, but there is no doubt that maternal request has a big impact on CS for less than completely normal circumstances. Jackson and Irvine demonstrated that 38% of all elective CS done in a district general hospital in the UK were for maternal request in the absence of any contra-indication to vaginal delivery, mostly in women with previous CS scars, and we know from Australia and the US that 50% of women with a previous CS will request another one.
It is perhaps not so surprising that women are becoming intolerant of risk when one thinks how ‘expectant’ we have all become. Our lives are more safe and controlled now than even before: perinatal, infant and maternal mortality are at an all time low in the developed world, and we can plan our families and have prenatal diagnosis to reduce the likelihood of abnormality. It is, therefore, understandable, that some people will request a medicalised, controlled and safe method of delivering their baby.
Those who favoured technology over nature were comfortably in the majority. Cost and effectiveness issues need to be considered alongside woman’s views. If the two conflict obstetricians should support the woman not the auditor.
The trend for use of caesarean section, coupled with greater emphasis on individual autonomy has clearly progressed too far for a return to paternalistic directions to women on how they should give birth. Instead of emphasis should be on comparisons of the implications of vaginal versus CS delivery. The uptake of CS in women made aware if such information will clearly be more appropriate than any current ‘desirable’ targets.
One professional worry is that obstetricians are in danger of becoming technicians and shedding responsibility for their actions by ‘blaming’ patient choice.
Message to the Public
Emergency CS in labour is the worst of all worlds and should be avoided by appropriate antenaal planning and rigorous intrapartum care.
The risks of CS and labour are real but different, and if fully explained to the woman, she should be allowed to accept one set of risks over the other - after all she is the person who has to live with the consequences. An elective CS in a fit healthy woman is neither unsafe nor bad practice if she truly understands the risks involved and is adamant that she cannot accept the risks of labour or vaginal delivery.
Thistlewaite PA, Tarazi RY, Giordano FJ, et al [Univ of California, San Deigo]
Surgical Management of Spontaneous Left Main Coronary Artery Dissection
Ann Thorac Surg 66: 258-260, 1998
Spontaneous coronary artery dissection is a rare cause of ischemic heart disease and sudden death. It occurs predominantly in healthy, young women in the third trimester of pregnancy or in the early postpartum period. Cardiac risk factors are usually absent. Early recognition is essential because coronary artery bypass grafting may be life saving. Woman, 34, 12 weeks postpartum,was first seen after 18 hours of chest pain, with acute anterior wall myocardial infarction. Cardiac catheterization revealed a dissection of the left coronary artery extending into the left anterior descending artery. She underwent urgent bypass grafting, with bluish hemorrhage noticed over the left main coronary artery and distal left descending coronary artery, at operation. She was discharged on the sixth postoperative day. Transthoracic echocardiography after two months, indicated improvement in both wall motion and ejection fraction.
Most cases of primary coronary dissection occur in peripartum women without known cardiovascular risk factors. Young patients seen with acute ischemic symptoms should be considered for urgent angiography. If left main coronary artery dissection is deected, bypass grafting is safe and effective. Rapid diagnosis and surgical intervention are lifesaving.
KS Joseph, et al (Lab Centre for Disease Control, Ottawa, Ont, Canada; McGill Univ, Montreal; Laval Univ, Quebec; et al )
Determinants of Preterm Birth Rates in Canada from 1981 through 1983 and from 1992 through 1994
N Engl J Med 339:1434-1439, 1998.
Data from the Statistics Canada live-birth and stillbirth databases were used.
There was a relative increase of 9% in the years studied, as preterm births increased from 6.3% of live births in earlier period to 6.8% in later period. There was a 5% increase among preterm singleton births. There was a 25% increase in the rates of preterm births among live births resulting from multiple gestation.
Conclusion- Changes in the frequency of multiple births, obstetrical intervention, and the use of ultrasound based estimates of gestational age were found to be factors that influenced the recent increase in preterm births in Canada between the years 1981 to 1994.
PGR Seaward, for the term PROM study Group (Univ of Toronto)
International Multicenter Term Premature Rupture Of Membranes Study : Evaluation of Predictors of Neonatal infection in Infants Born to Patients with Premature Rupture of Membranes at Term.
Am J Obstet Gynecol 179:635-639, 1998
Factors associated with the development of neonatal infection after premature rupture of the membranes were studied.
Four different strategies of treatment were compared: oxytocin induction, prostaglandin induction, and expectant management with oxytocin or prostaglandin, if necessary. The results showed no differences in the rates of neonatal infection or cesarean section. All women were at 37 weeks’ gestation when their membranes ruptured; each had a singleton fetus in cephalic presentation with no preexisting complications. Before randomization, the patients underwent a nonstress test and culture of vaginal or introital swabs for group B streptococci.
In addition to clinical signs of infection, a diagnosis of definite infection required 1 or more of the following: a positive culture from blood, CSF, urine, tracheal aspirate, or lung tissue; a positive Gram stain from CSF; a positive antigen-detection test from blood, CSF or urine; or a radiographic or histologic diagnosis of pneumonia. Criteria for probable infection were high or low blood neutrophil count, high immature-to-total neutrophil ratio, high actual immature neutrophil count, or specified CSF abnormalities.
Results showed the rate of definite or probable neonatal infection in 5,028 patients was 2.6%. Factors independently associated with neonatal infection were clinical chorioamnionitis, positive maternal culture for group B streptococci, 7 to 8 vaginal digital examinations, active labor more than 24 hrs after rupture of membranes, and maternal administration of antibiotics before delivery.
It was concluded for patients with group B streptococcal colonization, immediate induction with oxytocin and intrapartum antibiotic prophylaxis may be effective.
JM Alexander, LC Gilstrap, SM Cox, et al (Univ of Texas, Dallas)
Clinical Chorioamnionitis and the Prognosis for Very Low Birth Weight Infants.
Obstet Gynecol 91:725-729, 1998.
Findings of the group study – that there is a relation between chorioamnionitis and several indices of morbidity in very low birth weight infants. In this study, the preterm infants born to mothers with chorioamniotis were 2-3 times more likely to have morbidity than infants born to mothers who did not have chorioamnionitis. It appears that the brains of very low birth weight infants are especially susceptible to neurologic damage from chorioamnionitis.
Infants exposed to clinical chorioamnionitis are much more likely to have seizures, intraventricular hemorrhage, and periventricular leukomalacia. These findings are consistent that preterm and term infants who are exposed to chorioamnionitis are much more likely to have cerebral palsy develop later. Although the administration of antibiotics to the mother has been shown to reduce neonatal sepsis, respiratory illness, and necrotizing enterocolitis, it has not reduced the risk of intraventricular hemorrhage.
Multiple studies have shown that the positive predictive value of changes in the white cell count or of the immature/total neutrophil ratio is extremely low, although the absence of an abnormal white cell count is a useful negative predictor.
MS Cooperstock, et al (Univ of Missouri, Columbia; Missouri Dept of Health, Jefferson City; Natl Inst of Child Health and Human Development, Bethesda, Md)
Effects of Fetal Sex and Race on Risk of Very Preterm Birth in Twins.
Am J Obstet Gynecol 179:762-765, 1998.
Research has shown that a disproportionately high number of singletons born prematurely are male. Whether the risk of twin preterm birth correlates with the number of male fetuses was studied retrospectively.
Data obtained on 8000 white and 2000 black twin pregnancies registered in the Missouri Successive Pregnancy Birth/Death Data Set between 1978 and 1990 was used.
In twin gestations among white women, the number of male fetuses is linearly associated with the likelihood of birth before 35 weeks’ gestation. This suggests a fetal mechanism for preterm birth, linked to fetal sex. Thus, studies of preterm birth mechanisms must stratify fetuses by sex and race.
MA Klebanoff, et al (Natl Inst of Child Health and Human Development, Bethesda, Md; Univ of Southern California, Los Angeles; Univ of Copenhagen; et al).
Father’s Effect on Infant Birth Weight
Am J Obstet Gynecol 178:1022-1026, 1998.
The father’s size during young adulthood and, even more, at his own birth, are associated with infant birth weight. The influence of the father’s physical stature was independent of maternal size. Both paternal and maternal adult heights and body mass index were correlated. Fathers appear to influence the size of their babies primarily by regulating the intrauterine growth rate.
Editorial comment: In this article, the father’s physical stature, independent of maternal size, is shown to influence the birth weight of his children. More interestingly, his own size at birth has an influence. Although being bigger is not always better, it is, at least, something of measurable consequence attributed to the male partner on procreation. Now some serious attention must be paid to the effect of the father on the infant’s birth outcome.
KR Kardel, T Kase (Univ of Oslo, Norway)
Training in Pregnant Women: Effects on Fetal Development and Birth.
Am J Obstet Gynecol 178:280-286, 1998
A total of 42 well-trained athletes who had performed intense exercise before conception with a large part of the body’s muscle mass involved were studied. During pregnancy and until 6 weeks after delivery, the women followed either a high or medium intensity exercise program. The effect of the 2 different intensity levels of exercise during pregnancy on the fetus and mother were recorded, as well as the onset and length of labor, birthweight, and Apgar score.
During pregnancy, healthy and well-conditioned women may exercise without compromising fetal growth and development, as judged by birth weight, and without complicating the course of pregnancy or labor. Future studies should conduct a comparison with a non-exercising group. These findings may have limited value for the general population.
GCS Smith, et al (Cornell Univ,Ithaca, NY; Univ of Glasgow, Scotland)
First-Trimester Growth and the Risk of Low Birth Weight
N Engl J Med 339:1817-1822, 1998.
Women who had no important medical problems, a normal menstrual history, and a first-trimester ultrasound scan in which the crown-rump length of the embryo or fetus had been measured were identified. The relationship between the outcome of 4200 pregnancies and the difference between the measured and the expected crown-rump length in the first trimester, expressed as equivalent days of growth, was examined.
Conclusion drawn was that low birth weight, low birth weight percentile, and premature delivery may be associated with suboptimal first-trimester growth. This may be caused by the idea that the pathophysiology of extremely premature delivery may be different from that of moderately premature delivery. A possible causal relation between poor first-trimester growth and low birth weight may be a suboptimal environment or a disorder of placentation with suboptimal transfer of nutrients to the fetus.
VK Minior, MY Divon (Albert Einstein College of Medicine, Bronx, NY; Lenox Hill Hosp, New York)
Fetal Growth Restriction at Term: Myth or Reality ?
Obstet Gynecol 92: 57-60, 1998.
The result of the study and the editorial comment and conclusions – Morbidity is increased in small for gestational age (SGA) infants born at term after an uncomplicated pregnancy compared with matched appropriate for gestational age infants. These data challenge the notion that term growth restriction is benign.
Minior and Divon confirmed that these SGA infants from uncomplicated pregnancies have increased neonatal morbidity, including hypoglycemia, thrombocytopenia, and hyperbilirubinemia. More of them were depressed at birth and required admission to the neonatal intensive care unit, dispelling the “notion that term growth restriction is a benign condition.”
III Naef RW, JR Allbert, EL Ross, et al (Univ of Mississippi, Jackson; Carolinas Med Ctr, Jackson, Miss; Keesler US Air Force Med Ctr, Jackson, Miss)
Premature Rupture of Membranes at 34 to 37 weeks’ Gestation: Aggressive Versus Conservative Management.
Am J Obstet Gynecol 178:126-130, 1998.
Background: There has been no consensus about how to treat premature rupture of membranes that occurs between 34 and 37 weeks’ gestation.
The subjects were 120 women with singleton pregnancies who experienced PROM between 34 weeks, 0 days and 36 weeks, 6 days of gestation.
The findings were subjects in the conservative management group experienced significantly more chorioamnionitis (16% vs 2%) and had a significantly longer hospital stay (5.2 ± 6.8 vs 2.6 ± 1.6 days). Neonatal outcomes did not differ significantly between the groups, except for a lower cord blood pH in the observation group. None of the infants in the aggressive management group developed sepsis whereas 3 infants in the conservative management (5%) group developed this complication.
The induction of labor was a safe treatment that reduced maternal chorioamnionitis, shortened the mother’s hospital stay, and did not produce sepsis in the infant. Thus induction of labor should be considered for patients who experience PROM between 34 and 37 weeks’ gestation.
When membranes rupture at term, 70% of women begin labor within 24 hours and 95% begin it within 72 hours. The latency increases with preterm premature rupture of membranes, so that at 20 to 26 weeks’ gestation the mean latency period is 12 days, and at 32 to 34 weeks’ gestation it is only 4 days.
The consequences of this latency for the fetus are varied and range from sepsis and minor deformations to pulmonary hypoplasia and periventricular leukomalacia. This is specially seen in PROM occurs very early.
CD Naylor, for the Toronto Trihospital Gestational Diabetes Project Investigators (Sunnybrook Health Science Centre, North York, Ont, Canada; et al)
Selective Screening for Gestational Diabetes Mellitus
N Engl J Med 337: 1591-1596, 1997.
Screening all pregnant women for gestational diabetes mellitus is expensive, time-consuming, and uncomfortable for patients.
The 3,131 pregnant women in the study were randomly allocated to either derivation or validation group. Risk factors of the derivation group – age, race, body mass index, parity, family history of diabetes, and adverse obstetrical history were used to establish new screening strategies based on clinical scores that divided women into 3 risk groups: low, intermediate, and high.
Low-risk women were not screened and intermediate-risk women received the usual care. Women with plasma glucose levels of 130 mg/dL or high-risk women with plasma glucose levels of 128 mg/dL received universal screening. The strategies were evaluated by using the validation group.
According to multivariate analysis, age, race, and body mass index were independent predictors of gestational diabetes mellitus. The new strategy allowed 34.7% of women to avoid screening, and detected between 81.2% and 82.6% of women with gestational diabetes, with false positive rates of 15.4 and 16.0%. Usual care detected 78.3% of women with gestational diabetes, with a false positive rate of 17.9%.
Conclusion – These new strategies, which take women’s clinical characteristics into account, allow efficient and accurate screening for gestational diabetes mellitus in pregnant women.
Editorial comment : There is also an increased risk for the development of obesity and abnormal glucose tolerance in the offspring of women with gestational diabetes as early as the teenage years. The low-risk group comprised women who are less than the age of 25, not obese, have no family history in a first degree relative of diabetes, and are not members of an ethnic or racial high risk group, i.e. Hispanic, Native American, Asian or black.
GA Harrison, KE Humphrey, N Jones et al (Macquarie Univ, North Ryde, Australia; Univ of New South Wales, Sydney, Australia; Royal Women’s Hosp, Carlton, Australia)
A Genomewide Linkage Study of Preeclampsia/Eclampsia Reveals Evidence for a Candidate Region on 4q.
Am J Hum Genet 60:1158-1167, 1997.
A region on the long arm of chromosome 4 has been identified as a strong candidate region for the preeclampsia/eclampsia syndrome. This finding needs to be replicated in other pedigrees before it is accepted as a true linkage.
BM Sibai, for the National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units (Univ of Tennessee, Memphis; Univ of Chicago; Univ of Alabama, Birmingham; et al)
Risk Factors for Preeclampsia, Abruptio Placentae, and Adverse Neonatal Outcomes Among Women with Chronic Hypertension.
N Engl J Med 339:667-671, 1998.
Conclusions – In pregnant women with chronic hypertension, a diastolic blood pressure of 100 mm Hg or more early in pregnancy, hypertension of 4 years’ or more duration, and preeclampsia during a previous pregnancy are risk factors for preeclampsia. Furthermore, proteinuria early in pregnancy is a risk factor independent of preeclampsia.
The comment by Dinesh M Shah: Furthermore, the results show that women with proteinuria at entry into the trial were more likely to deliver at less than 36 weeks of gestation (35% vs 16%, with an odds ratio of 3.1). The authors concluded that in women with chronic hypertension, the presence of proteinuria early in pregnancy is associated with adverse neonatal outcome independent of the development of preeclampsia. It is well recognised in the clinical practice that the presence of proteinuria in women with hypertension will influence the clinician’s decision to act to deliver early, resulting in interventional prematurity.
What is significant is the increased incidence of small for gestational age babies born to the women who had proteinuria. The fact remains that the presence of chronic proteinuria is reflective of chronic vasculopathy and, therefore, has an impact on fetal growth; however, development of superimposed preeclampsia is acute vasculopathy and may not reflect prolonged reduction in uteroplacental perfusion.
Authors suggested that hypertension, significant proteinuria, or both are associated with a decrease in placental blood flow, which may be the common denominator for all of these deleterious effects such as an increase in stillbirth rate, perinatal mortality rate, and frequency of intrauterine growth retardation and neonatal morbidity. They found that the adverse outcome group had higher systolic pressure as early as 10 to 19 weeks of gestation and higher systolic and diastolic pressures as early as 20 to 24 weeks of gestation. In their study, serum uric acid of 6mg/dL or greater had a relative risk of 4.2 for adverse perinatal outcome.
Dinesh Shah fails to understand why the use of anti-2hypertensive therapy was not identified as a predictor of adverse perinatal outcome in the study by Sibai et al.
S Caritis, and the National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units (Univ. of Pittsburgh, Pa)
Low-Dose Aspirin to Prevent Preeclampsia in Women at High Risk.
N Engl J Med 338:701-705, 1998.
Objective: Although prophylaxis with low-dose aspirin has been recommended for preventing preeclampsia, a large trial failed to detect any major benefit of low-dose aspirin, possibly because of the inclusion of women at low-risk for preeclampsia. Whether aspirin therapy reduces the incidence of preeclampsia in women at increased risk was examined in a double-blind, randomized, placebo-controlled trial.
Between weeks 13 and 26 of pregnancy, 2539 women at high risk for preeclampsia because of pregestational insulin-treated diabetes mellitus, chronic hypertension, multifetal gestations, or previous preeclampsia, received 60 mg/day of aspirin.
Conclusion – Low dose aspirin did not reduce the incidence of preeclampsia in women at high risk for preeclampsia.
Dinesh M Shah comments that four categories considered at high risk for preeclampsia included pregestational insulin-treated diabetes mellitus, chronic hypertension, multifetal gestation, and preeclampsia in a previous pregnancy. The results showed that the incidence of preeclampsia in the aspirin and the placebo groups was similar for each of the 4 high risk categoreis. Furthermore, the incidences of perinatal death, preterm birth, and delivery of small for gestational age infants were similar in the 2 groups.
The same group of investigators, under the auspices of Maternal-fetal medicine units Network, also investigated the prevention of preeclampsia with low-dose aspirin in healthy nulliparous pregnant women. That study also revealed that, in general, this approach was not an effective strategy for prevention of preeclampsia, but it revealed a small benefit limited to a very small subset of women with elevated systolic blood pressure at entry into the trial. Furthermore, that study revealed that perinatal mortality was not improved, and there was an increased risk of abruptio placentae with the use of aspirin.
Limitations of both of these studies were that actual levels of salicylate in the blood were not measured, and the biochemical effect in terms of reducing thromboxane or altering the prostacyclin thromboxane ratio was not investigated.
Results indicate that antiplatelet therapy is not justifiable, either for the prevention of preeclampsia or for the purpose of reducing perinatal mortality.
L Verma, F Macdonald. P Leedham, et al (Birmingham Heartlands Hosp, England)
Rapid and Simple Prenatal DNA Diagnosis of Down’s Syndrome.
Lancet 352: 9-12, 1998.
Since the 1970s, cultured amniotic fluid cells obtained by amniocentesis at around 16 weeks of gestation have been used for the prenatal diagnosis of down’s syndrome by Karyotyping. This approach requires 10 mL of fluid, and it takes an average of 15 days for the results to be known. A new approach involves polymerase chain reaction (PCR) amplification of small-tandem-repeat markers located on chromosome 21 and analysis with fluorescence based methods. With this technique, results are available on the same day and only a small amount of fluid is required. The use of this approach for the diagnosis of trisomy 21 was investigated in a series of more than 2000 samples of amniotic fluid
Two DNA markers gave an informative and correct result in 2,083 of 2,139 samples (97.4%), in which 30 fetuses were identified as having trisomy 21 Down’s syndrome and 2,053 fetuses were identified as normal. In 32 of 41 other clear samples, an extra marker was informative. With these 3 markers, a total of 99.6% informative results were achieved. No false negative or false positive results were seen.
Authors conclude -For improved prenatal diagnosis of Down’s syndrome, the PCR-based DNA diagnostic test has great potential. The advantage is that results may be available within a day.
The PCR has revolutionized the practice of molecular genetics. Similar techniques could be employed simultaneously for the prenatal diagnosis of other common aneuploidies such as trisomy 13 and trisomy 18. PCR based prenatal diagnosis of trisomy 21 (as an adjunct to conventional cytogenetic analysis) is cost-effective and that the tremendous time saving. Rapid prenatal diagnosis of trisomy 21 through fluorescence in situ hybridization (FISH) is already a relatively well-established procedure in the United States.
MJ Hussey, ES Levy, et al (Rush-Presbyterain-St.Luke’s Med Ctr, Chicago)
Evaluating Rapid Diagnostic Tests of Intra-amniotic Infection: Gram Stain, Amniotic Fluid Glucose Level, and Amniotic Fluid to Serum Glucose Level Ratio.
Am J Obstet Gynecol 179:650-656, 1998.
After studying one hundred twenty-seven patients in preterm labor and 26 with preterm premature rupture of the membranes, the authors came to the conclusion that the diagnostic values of amniotic fluid glucose and the ratio of amniotic fluid to serum glucose were equivalent. However, Gram stain is superior to both. Combining Gram stain with amniotic fluid glucose level is superior to any individual test.
Ymd Lo, NM Hjelm, C Fidler, et al (Univ of Hong Kong, China; John Radcliffe Hosp, Oxford, England)
Prenatal Diagnosis of Fetal RhD Status by Molecular Analysis of Maternal Plasma.
N Engl J Med. 339: 1734-1738, 1998.
Rhesus (Rh) isoimmunization still occurs, despite the widespread use of Rh immune globulin prophylaxis in RhD negative pregnant women. It would be useful to determine the RhD status of these infants because no further testing or therapeutic procedures would be necessary if the infants were RhD-negative. The feasibility of fetal RhD genotyping with the use of fetal DNA extracted from plasma samples from RhD negative pregnant women was assessed.
Method: The study included 57 RhD negative pregnant women and their singleton fetuses: 12 were in their first trimester; 30 were in their second trimester; and 15 were in their third trimester. An analysis was conducted for the RhD gene with a PCR test sensitive enough to detect the RhD gene in a single cell from DNA extracted from maternal plasma. Serologic analysis of cord blood or PCR analysis of amniotic fluid was used to determine fetal RhD status.
Results : The results of RhD PCR analysis of maternal plasma DNA were completely concordant with the results of serologic analysis in the samples obtained from women in their second or third trimester of pregnancy. Two of the maternal plasma samples collected in the first trimester contained no RhD DNA, but the fetuses were RhD-positive. The other 10 samples were found to be concordant; 7 were RhD-positive and 3 were RhD negative.
Conclusion: Noninvasive fetal RhD genotyping can be performed rapidly and reliably with the use of maternal plasma at the beginning of the second trimester of pregnancy. Not only is the method is reliable but also rapid.
TD Shipp, BR Benacerraf (Massachusetts General Hospital, Boston; Brigham and Women’s Hospital, Boston; Harvard Med School, Boston)
The Significance of Prenatally Identified Isolated Clubfoot: Is Amniocentesis Indicated?
Am J Obstet Gynecol 178:600-602, 1998.
Most fetuses with clubfoot have other malformations, often associated with karyotypic abnormalities.
Patients: The 9-year review included 87 fetuses with isolated clubfoot identified on prenatal Ultrasound. Follow-up information was available on 68 fetuses. At birth, 38 fetuses were correctly identified as having bilateral clubfoot and 15 as having unilateral clubfoot. Eight fetuses with a ultrasound diagnosis of clubfoot were found to be normal at birth. In utero karyotyping was performed on 34 fetuses, 4 of which had abnormal karyotypes. The abnormal karyotypes identified were 47 XXY, 47 XXX trisomy 18, and trisomy 21.
The authors conclude that a 6% incidence of karyotypic abnormalities among fetuses with a ultrasound finding of isolated clubfoot was found. These fetuses should be karyotyped even if clubfoot is the only apparent congenital anomaly. Ultrasound used prenatally for the detection of clubfoot has a false-positive rate of 12%; the false-negative rate is unknown.
Budorick et al report on the value of 3-dimensional ultrasound of the fetal distal lower extremity, normal and abnormal. Three-dimensional ultrasound improves one’s ability to evaluate the lower limb.
AG Hadley, A Wilkes, et al (Internatl Blood Group Reference Lab, Bristol, England; The Bristol Blood Centre, England; St. Michael’s Hosp, Bristol, England)
The Ability of the Chemiluminescence Test to Predict Clinical Outcome and the Necessity for Amniocenteses in Pregnancies at Risk of Haemolytic Disease of the Newborn.
Br. J Obstet Gynaecol 105: 231-234, 1998.
The results of the study show that chemiluminescence testing was better correlated with the clinical outcome of hemolytic disease than was AutoAnalyzer testing. Chemiluminescence correctly identified 94% of unaffected fetuses, compared with 73.5% with the AutoAnalyzer. Prediction of severely affected cases were 97% vs.85% respectively. Neither test correctly distinguished unaffected from mildly affected cases.
Comments: The first step is to establish antibody levels in maternal serum to determine if amniocentesis or percutaneous umbilical cord sampling is indicated. Traditionally, anti-D levels have been measured by AutoAnalyzer, but cellular assays such as the chemiluminescence test (CLT) measure the biological activity of the antibodies; thus, they should be more reliable.
SL Clark, W Xu, TF Porter, et al (Univ of Utah, Salt Lake City)
Institutional Influences on the Primary Cesarean Section rate in Utah 1992 to 1995
Am J Obstet Gynecol 179: 841-845, 1998.
The review covered all deliveries occurring in general acute-care hospitals in Utah from 1992 to 1995.
It was found that cesarean delivery rates declined significantly during the study period. Factors reducing the cesarean delivery rate on 1-way analysis of variance were availability of a newborn ICU and maternal-fetal medicine subspecialists; presence of obstetrician-gynecologists on staff rather than family physicians only; delivery volume of greater than 1500 per year; urban location; and 24-hour in-house anesthesiology services. Thus there was a fall in percentage of cesarean section of 18% in 1990 to 15% in 1997 in LDS hospital.
MJ Paech, R Godkin, S Webster (King Edward Mem Hosp for Women, Perth, Australia)
Complications of Obstetric Epidural Analgesia and Anaesthesia: A Prospective Analysis of 10,995 cases.
Int J Obstet Anesth 7: 5-11, 1998.
During a 5-year period, prospective data were collected on 10,995 obstetric epidural blocks performed for labor in 1 institution. During this period, the epidural analgesia rate during labor was 33% to 36%, and the cesarean section rate was 18% to 23%.
Epidural analgesia for labor was the primary indication for 7648 women, whereas for 3311 women, the primary indication for anesthesia was cesarean section. Failed or abandoned insertion occurred in 0.5%, reinsertion in 5%, inadequate anesthesia in 1.7%, and inadequate analgesia in 0.9%. In addition to its minor complications there are 8 occasions, unexpectedly high blocks occurred comprising of 0.07% with 2 women requiring intubation and ventilation. Mild respiratory depression after postoperative epidural opioid occurred in 3 women.
Conclusion: An effective obstetric epidural service is possible with few serious complications. Maternal mortality is now rarely caused by epidural anesthesia. Current practices in obstetric epidural analgesia and anesthesia are safer than in the past.
J Berard, P Dufour, D Vinatier, et al (Hopital Jeanne de Flandre, Lille cedex, France)
Fetal Macrosomia: Risk factors and Outcome: A Study of the Outcome Concerning 100 Cases > 4500 g.
Eur J Obstet Gynecol Reprod Biol 77: 51-59, 1998.
Method: A retrospective review was conducted of 100 infants with weights of at least 4500g. The mode of delivery and incidence of maternal and perinatal complications were reviewed. Ten of these infants had a birthweight of more than 5000g. The mean birthweight was 4730g and the maximum was 5780g.
Results : In 19 mothers, gestational diabetes was present. In 3 women, diabetes was present. In 87 women, a trial of labor was allowed, and 13 women had elective cesarean delivery. The overall cesarean rate was 36%, which included elective cesarean delivery and failed trial of labor. Vaginal deliveries were performed in 73% of those having a trial of labor. In 14 infants, shoulder dystocia occurred in 22% of vaginal deliveries. In this series, it was the most frequent complication. Five infants had Erb’s palsy with humeral fracture associated in 1 infant.
Conclusion: For infants with estimated birthweights of less than 5000g and a trial of labor, vaginal delivery is a reasonable alternative to elective cesarean section. Elective cesarean section should be recommended for fetuses with an estimated birthweight of more than 5000g, particularly in primiparous women.
Gregory and colleagues identified term, singleton, macrosomic (at least 4000g) infants from Washington State and found that the incidence was 13%. Macrosomia appears to be the single important factor associated with shoulder dystocia which, even in the presence of significant risk factors, remain largely unpredictable.
MH Beall, C Spong, et al (Harbor-Univ of California, Los Angeles)
Objective Definition of Shoulder Dystocia: A Prospective Evaluation.
Am J Obstet Gynecol 179: 934-937, 1998.
A potentially devastating obstetric complication- shoulder dystocia- occurs in 0.5% of births. Shoulder dystocia has been associated with maternal factors such as gestational diabetes, obesity, weight gain, prolongation of the second stage of labor, operative vaginal delivery, and macrosomia.
The authors have studied seven hundred twenty two vaginal deliveries in a 2-year period for head-to-body delivery time and use of ancilliary obstetric maneuvers. They found that there were 623 deliveries with no shoulder dystocia and 99 deliveries with shoulder dystocia. Shoulder dystocia group had all the fetal injuries. A diagnosis of shoulder dystocia was significantly associated with duration of the second stage of labor.
Editorial comment : The prolonged head-to-body time should not be difficult to document and should be documented to find out the real incidence of shoulder dystocia.
TS Nesbitt, WM Gilbert, (Univ of california, Davis; Univ of California, Berkeley)
Shoulder Dystocia and Associated Risk Factors With Macrosomic Infants Born in California.
Am J Obstet Gynecol 179: 476-480, 1998.
They have studied 175,886 vaginal births of infants weighting more than 3500g, of whom 6238 infants (3%) had shoulder dystocia in a 1-year period.
They came to the conclusion when counseling patients when macrosomia is suspected, this information on the incidence of shoulder dystocia and associated risk factors for a large statewide population may assist providers of obstetric care. A severe limitation in attempting to establish guidelines designed to prevent shoulder dystocia is the inaccuracy of estimating fetal weight.
Langer reported that the incidence of macrosomia was almost threefold greater among diabetic women (21.6%) than nondiabetics (7.6%), and he and Conway used an ultrasound estimated weight threshold (4250gm or greater) as an indication for elective delivery in diabetic women.
As the risks for birth trauma and asphyxia escalate with increased fetal growth, the recommendation for cesarean section, if the estimated weight of the fetus is more than 4500g appears justified. Nonetheless, 61% of such infants were delivered vaginally and relatively few were permanently injured.
Of note in the database is the fact that 44% of infants with brachial plexus injuries reported in the birth records did not have the diagnosis of shoulder dystocia recorded. This probably reflects both underreporting of shoulder dystocia and other mechanisms for injuries to the brachial plexus.
BM Petrikovsky, E Schneider, et al (New York Univ, Manhasset)
Cephalhematoma and Caput Succedaneum: Do They Always Occur in Labor?
Am J Obstet Gynecol 179: 906-908, 1998.
There were 7 instances of cephalhematomas and caput succedaneum that were identified prenatally. All patients had a comprehensive ultrasonographic examination that included an assessment of the fetal head and neck. A neonatologist confirmed the final diagnosis of cephalhematoma vs.caput succedeneum. To rule out intracranial bleeding or skull fractures, ultrasonography of the neonatal head was performed.
Results : In 5 infants, cephalhematomas appeared as an echogenic bulge posterior to the occipital region of the fetal head, and in 2 infants, they appeared at the temporal region of the fetal head. Forceps or vacuum extraction were not used on any of the affected infants. The formation of cephalhematoma was strongly associated with station of the presenting part, presence of asynclitism and increasing application to delivery time.
Conclusion: Cephalhematomas are believed to result from operative delivery, but they can also originate in utero and antepartum. An associated factor appears to be premature rupture of the membrane. Causes other than birth trauma include head compression by the uterine walls, as seen in the setting of oligohydramnios after premature rupture of membranes.
Editorial comments: To the uninitiated, and even the experienced observer, a cephalhematoma before delivery in the fetus may mimic an encephalocele.
Clinicians need to be alerted to another relatively uncommon but very dramatic complication most often associated with vacuum deliveries, namely subgaleal hematomas (SGH). Chadwick was able to identify 37 infants with subgaleal hematomas over a 24 year period. All except 1 of the neonates had instrumental deliveries; 89% had a vacuum extractor applied to the head at some stage of delivery (vs. 10% of the general population of births in Western Australia). There was also a significantly increased risk of failure of attempted vacuum extractions, so that 45% of the neonates also had forceps applied to the head. Head trauma such as skull fracture, intracranial hemorrhage, and cerebral edema, as well as neonatal encephalopathy were common associations and the presence of a coagulopathy increased the severity of the SGH e.g Hereditary clotting disorders, including hemophilia. Although there were some early deaths, the long-term outcome for the survivors was excellent.
MV Senat, S Minoui, et al (hopital Beclere Clamart,France)
Effect of Dexamethasone and Betamethasone on Fetal Heart Rate Variability in Preterm Labour: A Randomised Study.
Br. J Obstet Gynecol 105: 749-755, 1998.
The patients were 82 pregnant women (97 fetuses) who experienced mild to moderate premature contractions between 25 and 33 weeks’ gestation. All patients had intact membranes and all who experienced more than 5 contractions per hour were treated with albuterol. The women were randomized to receive either betamethasone (n=42) or dexamethasone (n=40) to enhance fetal lung maturation.
Patients receiving betamethasone received 4 intramuscular injections of 3 mg of betamethasone sodium and 3mg of betamethasone acetate, with 12 hours between injections. Patients receiving dexamethasone received 4 intramuscular injections of 4mg of dexamethasone acetate, with 12 hours between injections. At baseline, 24 to 48 hours, and 4 to 7 days after the first injection of either corticosteroid, cardiotocograms (CTGs) were performed and their results recorded to characterize fetal cardiac parameters.
It was found that overall fetal outcomes did not differ significantly between the 2 groups. None of the 44 infants in the dexamethasone group experienced any significant changes in FHR variability or other CTG parameters throughout their treatment. However, CTG parameters changed significantly in the 53 infants in the betamethasone groups; by 24 and 48 hours, long and short-term variations were significantly shorter than at baseline and there were significantly more accelerations of more than 10 beats/min.
Conclusions: At equivalent doses, dexamethasone was associated with significantly less alteration in FHR variability than betamethasone. Both drugs effectively prevented respiratory distress.
The authors imply that, all things being equal-which they never are – dexamethasone is more desirable because it causes less FHR abnormalities. The potential blunting of the ability to recognize fetal distress by reducing FHR variability is not the major concern; we remain more concerned with the potential arrest of fetal head growth, particularly with multiple courses of these corticosteroids. It is imperative to determine whether multiple doses are necessary and if so, the safest interval between courses of antenatal steroids.
A Babinszki, et al (Mount Sinai School of Medicine, New York)
Prognostic Factors and Management in Pregnancies Complicated with severe Kell Alloimmnization: Experiences of the Last 13 years,
Am J Perinatol 15:695-701,1998.
The leading causes of fetal and neonatal anemia are sensitization to D, Kell, c, and E.
Among fetuses with Kell, a significantly higher incidence of polyhydramnios was found. The maternal serum titers were much lower in the Kell group than in the RhD group. The Kell sensitized fetus’s condition was not reliably reflected by a change in optical density (OD) 450 values. In the Kell group there was no intrauterine deaths or neonatal direct hyperbilirubinemia. In the RhD group, the hemolytic disease of the newborn was more severe. Ascites, skin edema, and pericardial effusion were equally present in the 2 groups.
Conclusion: In women with Kell isoimmunization, the course of the hemolytic disease had a better prognosis when compared with the women in the RhD group.
Editor’s comment: the pathophysiology of Kell sensitzation is caused by suppressed fetal erythropoiesis rather than accelerated fetal red cell production secondary to hemolysis. Fetal pleural effusion was not seen in sensitized Kell pregnancies and newborn transfusion was not required.
The author’s prenatal management includes determination of the consort’s Kell hemozygosity and confirmation of fetal Kell-positive status in a Kell-negative mother by DNA analysis of fetal amniocytes if the father is heterozygous.
Antenatal Diagnosis of Velamentous Umbilical Cord Insertion and Vasa Previa with Color Doppler Imaging. Nomiyama M, (Saga Prefectual Hosp Kouseikan, Japan) Ultrasound Obstet Gynecol, 12: 426-429, 1998.
Conclusion: In this study of 87 fetuses at 18-20 weeks gestation, cord insertion and velamentous cord insertion were consistently identified with colour Doppler imaging during routine sonography in the mid trimester. The identification of vasa previa required transvaginal color Doppler imaging and serial scans.
Editorial comments: Cord insertion has potentially valuable ultrasound observation and should be sought at the second trimester fetal ultrasound.
Newborn Shoulder Width: A prospective study of 2222 consecutive measurements.
E Verspyck, et al (Rouen Univ Hosp,Paris; Cochin Univ Hosp, Paris; Saint-Antoine Univ Hosp, Paris) Br.
J Obstet Gynaecol. 106: 589-593, 1999.
The incidence of shoulder dystocia ranges from 0.15% to 1.17% of all vaginal delivers. Few studies have attempted to identify the risk factors for this complication. In the current study, the predictive value of newborn shoulder width measurement in shoulder dystocia was investigated. The cutoff selected was 144mm or more with a sensitivity of 27.8%, a specificity of 91.8%, and a positive and negative predictive value of 4% and 99% respectively.
Conclusion: Even when shoulder width can be measured correctly antenatally such measurement has a low sensitivity for predicting shoulder dystocia. Newborn shoulder width measurement which is strong co-related with birthweight is still a poor independent indicator of shoulder dystocia.
Editorial comment: Maximum sensitivity of the prediction of shoulder dystocia occurs with birth weight of 4kg or more but with the disadvantage of 91% false positive rate. The data support the contention that any fetus at or above 5kg in body weight should be delivered abdominally to avoid the 50% risk of shoulder dystocia.
YMD Lo, et al (Chinese Univ of Hong Kong; Univ of Oxford, England).
Quantitative abnormalities of fetal DNA in maternal serum in preeclampsia.
Clin Chem 45:184-188, 1999.
Objective: Circulating nonhost DNA can be used as a marker for a variety of conditions and diseases. The concentration of circulating fetal DNA in preeclamptic pregnancy was investigated to study the pathologic processes that may influence the concentration of fetal DNA in maternal plasma.
Conclusion : Real time quantitative PCR is an accurate and effective method for detecting circulating fetal DNA. The method also has clinical applications for tumour derived DNA in cancer patients and donor-derived DNA in transplant patients.
Editorial comment: The reason for increased fetal DNA in preeclampsia generates some interesting speculations. The transfer rate of nucleated red blood cells and trophoblastic cells into the maternal circulation is known to be higher in preeclamptic women than in normotensive patients and fetal DNA in the maternal circulation may simply represent the product of nucelorrhexis of fetal cells in the maternal circulation. Maternal vascular pathology in the liver and kidneys – the most important sites for DNA removal may result in increased concentration of the resulting DNA fragments. This finding adds to the evidence of endothelial vascular pathology in preeclampsia. Also especially in the light of rapidity of withdrawal of fetal DNA from the maternal circulation, this approach may offer a means of establishing the severity of vascular disease and following its progression on a very fine time scale in women with pregnancy induced hypertension.
Does Gestational Hypertension Become Pre-eclampsia ?
P Saudan, et al (Univ of New South Wales, Sydney, Australia; Intstat Australia, Syndey, Australia) Br.
J Obstet Gynaecol, 105: 1177-1184, 1998.
The most frequent medical complication of pregnancy is hypertension. Preeclampsia is elevated blood pressure that occurs after 20 weeks of gestation with significant proteinuria or other organ dysfunction. It is difficult to know if a pregnant woman with new hypertension will progress to preeclampsia.
Conclusion: Preeclampsia will occur in 15 to 25% of women who receive an initial diagnosis of gestational hypertension and in this more likely with earlier presentation or when a women has had a previous miscarriage.
Editorial comment: This author defines gestational hypertension as hypertension occurring denovo past 20 weeks of gestational age but without albuminuria and disappearing within 3 months after delivery. The emergence of albuminuria hepatic hemolytic or CNS abnormalities suffices to change the diagnosis from gestational hypertension to preeclampsia and in contrast tot the generating benign course of gestational hypertension ushers in a period of genunine hazard to mother and fetus. The appearance for the first time of hypertension without albuminuria at or past 36 weeks of gestational represents a relatively benign finding which, with careful monitoirng be managed on a outpatient basis. Only an approximatley 10% risk of developing preeclampsia is seen in women with gestational hypertension diagnosed after 36 weeks of gestation.
H Cuckle, I Sehmi, R Jones (Univ of Leeds, England)
Maternal Serum Inhibin A can Predict Pre-eclampsia Br
J Obstet Gynaecol, 105: 1101-1103, 1998.
A biochemical marker to predict the development of preeclampsia would be useful. To date, none of the sufficient sensitivity and specificity has been identified. Median levels of maternal inhibin A in the second trimester blood samples of women who did and did not subsequently have preeclampsia were compared.
Conclusion: Maternal serum inhibin a levels can be increased months before the onset of symptoms of preeclampsia. The early natural history of preeclampsia can now be studied, and treatment trials considered.
Editorial comments: This is a serendipitous finding from this laboratory, long active in metabolic screening for fetal Down Syndrome. Using banked blood specimens from pregnant women obtained the Down Syndrome screening for which increases in diameric inhibin A activity are useful predictors, the authors followed a suggestion from another lab based on 20 preeclampsia and 20 controls where inhibin A activity was found strikingly elevated in the preeclamptics.
Authors hope to identify women destined to develop preeclampsia in the second trimester in order that longitudinal study of pathophysiology and trials of prophylactic therapy might be carried out before the development of the full blown syndrome.
BM Sibai, for the Natl Inst of Child Health and Human Development Network of Maternal-Fetal Medicine Units (Univ of Tennessee, Memphis)
Risk Factors for Preeclampsia, abruptio placentae, and adverse neonatal outcomes among women with chronic hypertension.
N Engl J Med 339: 667-671, 1998.
Conclusion: Risk factors for preeclampsia in women with chronic hypertension include diastolic blood pressure of at least 100 mmHg, hypertension of at least 4 years duration and a history of preeclampsia. The presence of proteinuria early in pregnancy and the development of preeclampsia in these women is associated with adverse neonatal outcomes.
High Prevalence of Hemostatic Abnormalities in women with a History of Severe Preeclampsia.
MG van Pampus, et al (Free Univ, Amsterdam)
Am J Obstet Gynecol, 180: 1146-1150, 1999.
Recent research has shown an increased frequency of hemostatic abnormalities in small groups of women with history of severe preeclampsia. The prevalence of such abnormalities in a large group of patients with a history of severe hypertensive disorder compared with an appropriate controlled group was determined.
Conclusion ; Hemostatic abnormalities which carry an increased risk of thrombosis occur in about 40% of the women with a history of severe preeclampsia which is nearly 4 times greater than in women with a history of uncomplicated pregancy. Such abnormalities may play an etologic role in preeclampsia.
Editorial comments; It is likely however that there is a relationship between abnormal hematologic factors measured here and pregnancy induced hypertension. It will take enough cases to avoid the mixing different subsets of patients and more clearly defined criteria for abnormality to clarify particular relationship among clotting factors to pregnancy induced hypertension and the strength of those relationships.
SZ Wiktor, et al (Ctrs of Disease Control and Prevention, Atlanta, Ga; Cote d’Ivoire Ministry of Public Health, Abidjan)
Short-course Oral Zidovudine for Prevention of Mother-to-Child Transmission of HIV-1 in Abidjan, Cote d’Ivoire: A Randomized Trial.
Lancet 353: 781-785, 1999.
The risk of mother-to-child HIV-1 transmission is high in Africa. A short course of perinatal oral zidovudine may reduce the rate of this transmission. The safety and efficacy of a short course of oral zidovudine among HIV-1- seropositive breast feeding women in Abidjan were reported.
Method: 280 patients received placebo or zidovudine in 300mg tablets. 1 tablet twice a day until labour onset, 1 tablet at labour onset and 1 tablet over 3 hours until the delivery. All infants were breast-fed.
Findings: The estimated risk of HIV-1 transmission was 21.7% in placebo group and 12.2% in the zidovudine group at 4 weeks and 24.9% and 15.7% respectively at 3 months. Efficacy at 4 weeks and 3 months was 44% and 37% respectively.
Conclusion: A short course of oral zidovudine appears to be safe and effective in reducing mother-to-child transmission of HIV infections at 3 months of age. The women tolerated this agent well. Successful, widespread implementation of this treatment will require substantial efforts.
F Dabis, for the DITRAME Study Group (Universite Victor Segalen Bordeaux 2, France; ORSTOM Petit Bassam, Abidjan; Centr Muraz, OCCGE, Bobo-Dioulasso, Burkina Faso; et al)
6-Month Efficacy, Tolerance and Acceptability of a Short Regimen of Oral Zidovudine to Reduce Vertical Transmission of HIV in Breastfed children in Cote d’Ivoire and Burkina Faso: A double-blind placebo controlled multicentre trial.
Lancet 353: 786-792, 1999.
Findings: The probability of HIV infection at 6 months of age was 18% among babies in the zidovudine group and 27.5% among those in the placebo group.
Conclusion: A short course of oral zidovudine in the peripartum period provides a 38% decrease in early vertical HIV-1 transmission, despite breast-feeding.
Editorial comments: For emerging nations, early detection of HIV positivity, the logistic of assuring regular prenatal care visits and drug administration, the use of IV administration during labour and neonatal treatment in multiple drug doses usually exceed available financial and health group personnel resources. The cultural norms that value nursing despite the estimated 7% to 14% increase in maternal-to-fetal transmission thought to occur by 3 months of age in infants nursed by HIV positive women.
Infant infection rate increased with age as the effects of breast milk transmission of the virus played its part. The lesser reduction in incidence rate exhibited by these West African studies makes clear the importance of avoiding nursing to preclude horizontal transmission from mother to infants in the postpartum period. On the other hand, these studies show that even when abbreviated, zidovudine therapy is quite effective in reducing vertical transmission.
NA Wade, et al (AIDS Inst, Albany, NY: New York State Department of Health, Albany; Univ of Albany, NY
Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of theHuman Immunodeficiency virus.)
N Engl J Med 339: 1409-1414, 1998.
Editorial comments: The important message is that women and their infants who have not benefited from intrapartum AZT may still be afforded some reduction in the incidence of newborn infection if therapy is begun during labour and before the third day of newborn life.
Efficacy of treatment of syphilis in pregnancy.
JM Alexander, et al (Univ of Texas, Dallas; Dallas County Health Dept, Dallas)
Obstet Gynecol 93:5-8, 1999.
Background: Current guidelines for treating syphilis in pregnant women are based on research conducted in the 1940’s and 1950’s which showed that a variety of penicillin based clinical regimens effectively prevent neonatal transmission of syphilis.
Method: Treatment was administered to 448 patients between 1987 and 1989. It consisted of 2.4m units of IM benzathine penicillin G for primary, secondary or early latent syphilis. The late latent disease was treated with 7.2m units of IM benzathine penicillin G over 3 weeks.
Conclusion: Overall, the current centres for disease control recommendations for preventing congenital syphilis and for treating maternal infection are effective. The risk of fetal treatment failure is greatest in women with secondary syphilis.
Editorial comments: Therapeutic failures occur in 5.3% of cases of maternal secondary syphilis and 2% of early (less than 1 year duration) latent infection at the time of treatment. There is the need for primary treatment as early in pregnancy as possible to make re-treatment feasible and effective.
Pregnant, vomiting and going blind.
S Tesfaye, et al (Royal Liverpool Univ Hosp, England)
Lancet 352: 1594, 1998.
Conclusion: Wernicke’s encephalopathy should be considered in any patient with a history of inadequate nutritional intake and visual loss and thiamine treatment should be initiated promptly. Thiamine supplements should be prescribed for women with hyperemesis gravidarum.
Editorial comments: This is a good reminder of the need to do fundoscopic examination in women with significant hyperemesis gravidarum. The hazard is that deficient vitamin B complex ingestion associated with hyperemesis together with the failure of protein caloric intake may lead to polyneuritis, a first finding of which is often flame-shaped fundal hemorrhages without visual impairment. Undetected, the deficiency state will progress because of blindness, ophthalmoplegia, and hyporeflexia. Therapy with vitamin supplements including thiamine produces rapid improvement and prevents the progression to even more serious CNS dysfunction.
D Dunn, et al (Univ College London; Hopital de la Croix-Rousse, Lyon, France; Statens Serum Institut, Copenhagen)
Mother-to-child transmission of toxoplasmosis : Risk estimates for clinical counselling.
Lancet 353: 1829-1833, 1999.
Reliable estimate of the risk of congenital toxoplasmosis infection and its clinical sequelae in women who acquire this infection during pregnancy are currently not available. Risk estimates for mother-to-child transmission of toxoplasmosis were determined for use in clinical counselling.
Findings: The overall maternal fetal transmission rate was 29%. Risk of transmission increased markedly with duration of gestation from 6% at 13 weeks to 72 % at 36 weeks. Fetuses infected early in pregnancy were much more likely to have clinical signs of infection. Women sero-converting between 24 and 30 weeks’ gestation had the greatest risk (10%) of having a congenitally infected child with early clinical signs and possible long term complications.
Editorial comments: Maternal diagnosis was based on the new appearance of immunoglobulin (Ig)M in serum, and gravidas with IgG were excluded as having been previously infected. Only 5% of the newly infected gravidas had symptoms. Fetal diagnosis was based on mouse inoculation of umblical vein blood (22-32 weeks gestational age) or of amniotic fluid (16-30 weeks gestational age), supplemented by PCR for toxoplasmosis DNA in amniotic fluid after 1994. All gravidas with IgM conversion were treated with spiramycin and fetuses were treated with pyrimethamine and sulfadiazine if converison occurred past the 32nd week of pregnancy.
The role of spiramycin in preventing fetal infection cannot be evaluated because of lack of controls. A recent analytical review finds no convincing evidence of benefit from maternal intrapartum prophylaxis for this disease. Prenatal screening for maternal toxoplasmosis is not recommended. Whether newborn IgM screening for toxoplasmosis infection is cost effective is also uncertain.
Incidence of Toxoplasma gondii infection in 35,940 pregnant women in Norway and Pregnancy Outcome for Infected women.
PA Jenum, et al (Natl Inst of Public Health, Oslo, Norway; Natl Hosp, Oslo, Norway; Ulleval Univ, Oslo, Norway; et al )
J Clin Microbiol 36:2900-2906, 1988.
The relatively high incidence of persisting IgM after pre-pregnancy infection and the low predictive value for IgM in pregnancy makes practical screening for toxoplasmosis impractical.
Balloon Mitral Valvotomy in Pregnancy: Maternal and Fetal Outcomes;
Gupta, et al (King Edward Mem Hosp, Mumbai, India)
J Am Coll Surg 187: 409-415, 1998.
Percutaneous BMV by Inoue method is safe and effective for treatment of severe mitral stenosis during pregnancy. This procedure provides marked symptomatic relief and yields excellent medical and fetal outcomes.
The second article:
The Prevalence of Polycystic Ovaries in Healthy Women.
R Koivunen, et al (Univ Hosp of Oulu, Findland; Helsinki City Maternity Hosp; Univ of Turku, Finland) Acta Obstet Gynecol Scand 78:137-141, 1999.
In healthy women, the prevalence of polycsytic ovaries varies with age. The findings are more common in women aged 35 years or young girls or than in those aged 36 years or older. It remains unclear if women with polycystic ovaries will later develop full-blown polycystic ovary syndrome; however, the hormonal parameters and clinical findings among women with polycystic ovaries mimicked those with polycystic ovary syndrome.
The results of this study of a group of women without the clinical manifestation of polycystic ovary syndrome (PCOS) found that 14% had ovaries with the sonographic appearance of polycystic ovaries (PCOs). Among women younger than 36 years, one fifth had ovaries that appeared polycystic when vaginal probe sonography was performed. None of this group of women had oligomenorrhea or infertility. Thus, clinicians need to differentiate women with PCOS from those with ovaries that have the sonographic appearance of PCO. As reported earlier, not all women with Polycystic Ovaries Syndrome have Polycystic Ovary and as shown in this study, not all women with Polycystic Ovary have Polycystic Ovary Syndrome.
The third article –
Transvaginal Ultrasound Appearances of the Ovary in Normal Women and Hirsute Women with Oligomenorrhoea.
Fox R (Univ of Bristol, England) Aust NZ J Obstet Gynaecol 39:63-68,1999.
Conclusion – In women with polycystic ovary disease, the classical ultrasound features are not consistently present, and the absence of increased follicularity at scan does not exclude a diagnosis of polycystic ovary. The diagnosis could be made with 15 or more small follicles per ovary. An expanded echogenic ovarian stroma was found in all the women with hirsuitism.
There are 2 articles on the impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.
1) Prevalence of Impaired Glucose Tolerance and Diabetes in Women with Polycystic Ovary Syndrome.
DA Ehrmann, et al (Univ of Chicago). Diabetes Care 22: 141-146, 1999.
2) Prevalence and Predictors of Risk for Type 2 Diabetes Mellitus and Impaired Glucose Tolerance in Polycystic Ovary Syndrome: A Prospective, Controlled Study in 254 Affected Women.
RS Legro, et al (Pennsylvania State Univ, Hershey; Brigham and Women’s Hosp, Boston) J Clin Endocrinol Metab 84:165-169, 1999.
Both these articles are reviewed by Editor, D.R. Mishell Jr, with a comment that similar results were found in these 2 studies in which oral glucose tolerance tests (OGTTs) were performed in 2 large groups of women with clinical and endocrinologic changes indicating the presence of polycystic ovarian syndrome PCOS.
In the study by Ehrmann et al with 35% of 122 young women with PCOS had impaired glucose tolerance and 10% had non-insulin dependent diabetes mellitus (NIDDM). In the study of Lego et al 31% of 254 young women of similar age had impaired glucose tolerance and 7.5% had diabetes. In both groups, the incidence of glucose abnormalities was higher in obese than nonobese women. It would appear advisable to perform an OGTT at the time of diagnosis of PCOS and periodically thereafter. If abnormalities in glucose metabolism are found, appropriate interventions, such as diet and exercise, should be recommended to prevent or delay the conversion of IGT to NIDDM. Individuals with NIDDM should have appropriate therapy.
MA Cobleigh, et al (Rush-Presbyterian-St Luke’s Med Ctr, Chicago)
Hormone Replacement Therapy and High S Phase in Breast Cancer
JAMA 281: 1528-1530, 1999.
Conclusion – Pre-existing clinically occult cancers may be promoted by the use of hormone replacement therapy, which may bring them to light sooner in their natural biological history. This may account for the better survival of patients with breast cancer who have used hormone replacement therapy. The use of hormone replacement therapy appears to stimulate growth of estrogen receptor-positive but not estrogen receptor-negative breast cancer. There is an unknown prognostic significance in current hormone replacement therapy users who have estrogen receptor-positive tumors.
Editorial comments: Some, but not all, observational epidemiologic studies indicate that the postmenopausal use of estrogen replacement is associated with an increased risk of diagnosis of breast cancer compared with women not taking estrogen. Several studies have reported that survival rates of women in whom breast cancer develops postmenopausally is significantly greater among women taking estrogen than among age-matched controls with breast cancer who are not taking estrogen.
Breast cancer with a high percentage of breast cells in S phase has been associated with a poor prognosis of the disease. This study found that estrogen use was associated with a high frequency of S-phase cells in the treated breast cancers. Since estrogen use is associated with a better prognosis for women with breast cancer, the authors speculate that estrogen may promote the growth of clinically occult cancers. These cancers are then treated earlier in their natural history than normally occurs, and survival rates are increased. Thus estrogen does not initiate breast cancer but promotes the growth of an existing cancer so that it can be diagnosed and treated earlier in its natural history.
Fertility Drugs and the Risk of Breast Cancer
E Ricci, et al (Instituto di Richerche Farmacologiche ” Mario Negri,’ Milan, Italy; Universita degli Studi di Milano, Italy) Hum Reprod 14: 1653-1655, 1999.
Use of fertility drugs does not increase the risk of breast cancer. These findings are consistent with the results of most, though not all, previous studies.
Fertility Drugs and the Risk of Breast and Ovarian Cancers : Results of a Long-term Follow-up Study.
G Potashnik, et al (Ben-Gurion Univ of Negev, Beer Sheva, Israel; Sheba Med Ctr, Tel Hashomer, Israel). Fertile Steril 71:853-859, 1999.
The relationship between fertility drug use and the risk of breast and ovarian cancers has not been defined. A historic-prospective cohort study was undertaken to investigate this association.
Conclusions- The use of fertility drugs appears to be unassociated with an increased risk of breast cancer. Women treated with human menopausal gonadotropin alone had no malignant tumors. These findings should be considered in light of the recent suggestion that clomiphene citrate may decrease the risk of breast cancer in infertile women.
Editorial comment: The data from this long-term prospective study indicate that the use of ovulation-inducing agents is not associated with an increased risk of either breast or ovarian cancer. Many women are concerned that the use of these agents may increase their risk of having these cancers. Data accumulating from this and other studies indicate that such a relation does not exist.
Patrick Rozenberg, Francois Goffinet, Mahdie Hessabi, Sage-Femme (Dept. of Gynecology & Obstetrics, Poissy Hospital, University Paris V).
Comparison of the Bishop score, ultrasonographically measured cervical length, and fetal fibronectin assay in predicting time until delivery and type of delivery at term.
Am J Obstet Gynecol 2000; 182:108-13.
Objective : The authors aim was to compare the Bishop score, fetal fibronectin assays, and ultrasonographic measurement of cervical length to determine the best markers for time until spontaneous labour at term and risk of cesarean delivery, especially for the indication of lack of progress of dilatation.
Study Design: This prospective study included 128 singleton vertex pregnancies with no clinical evidence of membrane rupture or regular contractions and a prenatal consultation between 39 weeks 4 days’ gestation and measured cervical length by transvaginal ultrasonography. The end points were the percentage of patients with a spontaneous onset of labour in the week after these tests and type of delivery.
Results: The spontaneous onset of labour within a 7day period was closely associated with a Bishop score ³6 and with a cervical length £ 26mm but not with a positive result of the fetal fibronectin assay. On the other hand, vaginal delivery was significantly associated with the fibronectin assay result but not with either the Bishop score or cervical length.
Conclusions: The Bishop score and ultrasonographic measurement of cervical length are valuable for predicting the onset of spontaneous labour within 7 days, whereas the fetal fibronectin assay is useful for evaluating the risk of cesarean delivery. These tests thus provide different physiologic data that are useful for different purposes.
Several studies have shown that a finding of absence of fetal fibronectin in cervicovaginal secretions is useful in predicting the risk of postterm birth. The duration of the first phase of labour is significantly lower among patients with fetal fibronectin in the secretions.
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.
David M Stamilio, Harish M Sehdev, Mark A Morgan, et al (Dept of Obstetrics and Gynecology, Philadelphia, Pennsylvania and Camden, New Jersey)
Can antenatal clinical and biochemical markers predict the development of severe preeclampsia ?
Am J Obstet Gynecol, March 2000, 182: 589-94
Study Design : The authors performed a retrospective cohort study of all pregnant patients with single gestations from 1995 through 1997 for whom we had complete follow-up data. Through medical record review they determined whether patients had severe preeclampsia develop according to American College of Obstetricians and Gynecologists criteria. Case patients with severe preeclampsia were compared with control subjects with respect to clinical data and multiple marker screening test results. With potential predictive factors identified in the bivariate and stratified analyses both an explanatory logistic regression model and a clinical prediction rule were created. Patients were assigned a predictive score according to the presence or absence of predictive factors, and receiver operating characteristic analysis was used to determine the optimal score cutoff point for prediction of severe preeclampsia with maximal sensitivity.
Results: Among the 1998 patients, the authors found 49 patients with severe preeclampsia with prevalence 2.5%/. After they controlled for confounding variables, case patients and control subjects had similar human chorionic gonadotropin and a-fetoprotein levels, and the only variables that remained significantly associated with severe preeclampsia were nulliparity (relative risk 3.8) history of preeclampsia (relative risk 5.0) elevated screening mean arterial pressure (relative risk 3.5) and low unconjugated estriol concentration (relative risk 1.7). Our predictive model for severe preeclampsia, which included only these 4 variables, had a sensitivity of 76% and a specificity of 46%.
Conclusion: Even after incorporation of the strongest risk factors, their predictive model had only modest sensitivity and specificity for discrimination of patients at risk for development of severe preeclampsia. The addition of the human chorionic gonadotropin and a-fetoprotein biochemical markers did not enhance the model’s predictive value for severe preeclampsia.
Steven L Clark, James R Scott, et al (Dept. of Perinatology, Salt Lake, Utah).
Is vaginal birth after cesarean less expensive than repeat cesarean delivery?
Am J Obstet Gynecol, March 2000;, 182: 599-602.
Study Design: Costs associated with All Patient Refined diagnostic-related groups and Current Procedrual Terminology for a large not-for-profit health care system were applied to an algorithm describing maternal and neonatal outcomes of trial of labour. Perinatal morbidity rates and cost estimates for long-term neurologic damage associated with uterine rupture were derived from published literature.
Results: If a 70% vaginal birth rate for women undergoing a trial of labor and delivery in a tertiary center with a mean uterine rupture to delivery time of 13 minutes is assumed, the net cost differential ranged from a saving of $149 to a loss of $217, depending on morbidity assumptions. For vaginal birth after cesarean success rates <70%, trial of labour in the presence of two previous cesarean section scars, and institutional factors increasing the perinatal morbidity rate by just 4% with respect to that seen in tertiary centers, trial of labor resulted in a net financial loss to the health care system regardless of all other assumptions made.
Conclusions: When costs as opposed to charges are considered and the cost of long-term care for neurologically injured infants is taken into account, trial of labor after previous cesarean is unlikely to be associated with a significant cost saving for the health care system. Recent government-mandated length-of-stay requirements are likely to make the economic benefit of vaginal birth after cesarean even less favourable. Factors other than cost must govern decisions regarding trial of labour or repeat cesarean.
Dr. Mrs.Ingle’s comment: I remember the words of our teacher Dr. C.G. Saraiya, who used to say, think 10 times before doing primary section but do not think even once when considering a repeat section.
Andrea G Witlin, George R Saade, et al (Dept of Obstetrics and Gynecology, Galveston, Texas and Memphis, Tennesse)
Predictors of neonatal outcome in women with severe preeclampsia or eclampsia between 24 and 33 weeks’ gestation.
Am J Obstet Gynecol, March 2000;, 182: 607-611.
The authors sought to characterize predictors of neonatal outcome in women with severe preeclampsia or eclampsia who were delivered of their infants preterm.
Study Design: The authors performed a retrospective analysis of 195 pregnancies delivered between 24 and 33 weeks’ gestation because of severe preeclampsia or eclampsia. Multiple logistic regression and univariate x 2 analysis were performed for the dependent outcome variables of survival and respiratory distress syndrome by use of independent fetal and maternal variables. A P value of < .05 was considered significantly.
Results: In the multivariate analysis, respiratory distress syndrome was inversely related to gestational age at delivery and directly related to cesarean delivery, whereas survival was directly related to birth weight. There was no correlation in the multivariate analysis between respiratory distress syndrome or survival and corticosteroid use, composite neonatal morbidity, mean arterial pressure, eclampsia, or abruptio placentae. In the univariate analysis respiratory distress syndrome was associated with cesarean delivery. The incidence of intrauterine growth restriction increased as gestational age advanced. Furthermore, intrauterine growth restriction decreased survival in both the multivariate and univariate analyses.
Conclusion: The presence of intrauterine growth restriction adversely affected survival independently of other variables. Presumed intrauterine stress, as reflected by the severity of maternal disease, did not improve neonatal outcome.
Robert L Goldenberg, William W Andrews, Brian M Mercer et al (Dept. of Obstetrics and Gynecology, Birmingham, Alabama, Cincinnati and Columbus etc.)
The Preterm Prediction Study: Granulocyte colony-stimulating factor and spontaneous preterm birth.
Am J Obstet & Gynecol, March 2000, 182: 625-30.
Granulocyte colony-stimulating factor is elevated in the amniotic fluid and plasma of women with chorioamnionitis and active preterm labor. The authors investigated the relationship between plasma granulocyte colony stimulating factor and subsequent spontaneous preterm birth in pregnant women without symptoms.
Study Design : The authors performed a nested case-control study involving 194 women who had a singleton spontaneous preterm birth and 194 matched term control subjects from the patient pool enrolled in the Preterm Prediction Study. Plasma collected at 24 and 28 weeks gestation was analysed for granulocyte colony stimulating factor, and the results were compared with subsequent spontaneous preterm birth.
Conclusion: In pregnant women without symptoms at 24 and 28 weeks gestation, elevated plasma granulocyte colony-stimulating factor levels are associated with subsequent early (<32 weeks gestation) spontaneous preterm birth, especially within the next 4 weeks, but not with late spontaneous preterm birth. These data provide further evidence that early spontaneous preterm birth is associated with an inflammatory process that is identifiable by the presence of a cytokine in maternal plasma several weeks before the early spontaneous preterm birth; however, later spontaneous preterm birth is not associated with this process.
K D Heyborne, Englewood, Colorado
Preeclampsia prevention: Lessons from the low-dose aspirin therapy trials
Am J Obstet Gynecol, 183(5), Sept.2000, p.523.
The ability of low-dose aspirin therapy to prevent preeclampsia is controversial. The 19 randomized, placebo-controlled trials of low-dose aspirin therapy reported in the literature were categorized according to the risk factors of the women studied-nulliparity, underlying medical illness, poor obstetric history, and multiple gestation. Low-dose aspirin therapy reduced the incidence of preeclampsia among women with poor obstetric histories and among high-risk nulliparous women but was ineffective among women with underlying medical illness. It was marginally effective among low-risk nulliparous women, and benefits for women with multiple gestations. The differential effects of low-dose aspirin therapy in the various risk groups are probably a result of varying roles in the groups of abnormal arachidonic acid metabolism in mediating preeclampsia. It is premature to abandon the use of low-dose aspirin therapy for preeclampsia prevention.
Recommendation regarding low-dose aspirin therapy use for preeclampsia prevention
Group Low dose aspirin Comment
Nulliparous, low risk No Minimal clinical benefit.
Nulliparous, high risk Yes Need better screening tests to identify women who
will benefit; consider use in nulliparous women with
serum hCG concentration >3.0 multiples of the
High risk, medical No
High risk, obstetric Yes
High risk, multiple
Gestation Optional More studies needed
E Ekerhovd, M Brannstrom et al (Goteborg, Sweden)
Nitric oxide synthases in the human cervix at term pregnancy and effects of nitric oxide on cervical smooth muscle contractility.
Am J Obstet Gynecol, Sept.2000; 183: 610-6
Objective: The purpose of the study was to determine whether a nitric oxide-generating system exists in the uterine cervix at term pregnancy and to study the effects of nitric oxide on contracting cervical strips.
Study Design: Tissue specimens were obtained from the cervices of women after deliveries and at elective cesarean deliveries. Immunohistochemcial techniques and immunoblotting were used to identify isoforms of nitric oxide synthase. The effects of nitric oxide on cervical contractility were examined by the addition of nitroglycerin or spermine NONOate [(Z)-1-(N-[3-aminopropyl]-N-[4-(3-aminopropyl-ammonio)butyl]-amino)-diazen-1-ium-1,2-diolate] to organ baths.
Results: Immunohistochemical examination demonstrated positive staining for both endothelial and inducible nitric oxide synthase. Both isoforms of nitric oxide synthase were clearly detectable by immunoblotting. Significant inhibition of contractile activity (10-7-10-5 mol/L) was observed when nitroglycerin or spermine NONOate was administered.
Conclusion: An endogenous nitric oxide system is present in the uterine cervix at term, and this tissue is responsive to nitric oxide, which causes relaxation of the cervical muscle.
Cervical ripening accomplished by local application of prostaglandins is commonly used to facilitate first-trimester surgical termination of pregnancy or to induce labor at term. A recently published randomized trial of the nitric oxide donor isosorbide mononitrate versus the prostaglandin analog gemeprost demonstrated that this specific nitric oxide donor not only caused adequate cervical ripening but also had fewer side effects than gemeprost. On the basis of their results, which have demonstrated the existence of a functional nitric oxide system within the human uterine cervix at term, the authors propose that there may also exist a clinical role for locally administered nitric oxide donors in induction of cervical ripening in pregnant women at term.
Nina Markovic, Roberta B Ness et al (Pittsburgh, Pennsylvania0
Substance use measures among women in early pregnancy
Am J Obstet Gynecol, 183: Sept.2000: 627-32
Objective : The authors purpose was to compare self-reported and biochemical measures for tobacco, marijuana and cocaine exposures among women early in pregnancy.
Conclusions: Urinary assays were equally likely to be positive among women reporting never use and those reporting past use of tobacco, marijuana, or cocaine. Thus women with a positive biologic assay result were as likely to deny use of tobacco as they were to deny marijuana, or cocaine.
J Waugh, I J Perry et al (Leicester and London, UK and Cork, Ireland)
Birth weight and 24-hour ambulatory blood pressure in nonproteinuric hypertensive pregnancy
Am J Obstet Gynecol, Sept.2000; 183: 633-7.
Objective: The aim of this study was to examine the relationship between maternal ambulatory blood pressure monitor measurements during pregnancy and birth weight in a population of women considered to have hypertension according to conventional antenatal clinic measurement.
Study Design: A total of 237 women were found to have hypertension (blood pressure ³140/90mm Hg) without significant proteinuria during examination in the antenatal assessment area. Sequential -day unit blood pressure recordings and a 24-hour automated ambulatory blood pressure recording were performed, and the results were compared with the principal outcome measure of birth weight.
Results: A significant inverse association (gradient, -13.5; 95% confidence interval -23.4 to -3.6) was found between daytime ambulatory diastolic blood pressure measurement and birth weight. An increase of 5mm Hg in daytime mean diastolic blood pressure was associated with a fall in birth weight of 68.5g. This association remained after adjustment for potential confounders that included maternal age, maternal weight, smoking status, ethnicity, and gestational age at delivery. No such association was found between obstetric day unit assessment of blood pressure and birth weight.
Conclusion: There is a significant association between blood pressure and birth weight in nonproteinuric hypertensive pregnancies. The best predictor of this association is the daytime mean ambulatory diastolic blood pressure measurement. This is further evidence that maternal blood pressure may be an important confounding and potentially genetic variable in the association between birth weight and subsequent adult hypertension.
D S McKenna, G M Wittber, et al (Columbus, Ohio)
The effects of repeat doses of antenatal corticosteroids on maternal adrenal function.
Am J Obstet Gynecol, Sept.2000; 183: 669-73
Objective: The purpose of this study was to determine whether repeated doses of maternal corticosteroids suppress the maternal hypothalamic-pituitary -adrenal axis.
Study Design: The low-dose corticotropin stimulation test (1.0 mg intravenously) was administered a median of 3 days after the last betamethasone dose to 18pregnant women who had received at least 2 weekly courses of antenatal betamethasone and to 6 control subjects matched for gestational age who had not received antenatal corticosteroids.
Results: The mean basal cortisol level was significantly depressed among women who had received betamethasone with respect to control subjects (1.9 ± 1.5 vs 26.5 ± 6.2 mg/dL; P<.001). The maternal cortisol level after corticotropin stimulation was significantly lower in all women who had received betamethasone (P<.001). The mean time to attainment of peak cortisol level was significantly longer among women who had received betamethasone than among control subjects (37 ± 6.8 vs 27.4 ± 1.6 minutes; P<.001).
Conclusions: Repeated courses of betamethasone lead to barely detectable maternal basal cortisol levels and secondary adrenal insufficiency.
Comment: This study indicates that in most cases basal 8AM cortisol levels during the third trimester of pregnancy can be used to accurately diagnose secondary adrenal insufficiency. The low-dose corticotropin stimulation test can be used when basal levels fall between 3 and 19 mg/dL.
The effects on human development from long-term maternal corticosteroid administration are uncertain. Antenatal corticosteroid should be repeated only in those pregnancies at the highest risk for preterm delivery. Furthermore, there are no data to support the use of corticosteroids for prophylactic indications.
JS Gorbach, FL Counselman, MH Mendelson (Eastern Virginia Med School, Norfolk)
Spontaneous Pneumomediastinum Secondary to Hyperemesis Gravidarum
J Emerg Med 15: 639-643 1997.
The authors report a rare case of Pneumomediastinum secondary to Hyperemesis Gravidarum. Pneumomedistinum itself is an infrequent diagnosis, occurring in about 1 in 25000 hospital admissions.
Pneumomediastinum complicating pregnancy has been reported during labour. In this case, the pneumomediastinum may be attributed to disruption of the loose connective tissue between cartilaginous rings and small bronchi and bronchioles. This extruded air then tracks along the pulmonary vasculature to the hilum and expands into the mediastinum. It must be remembered that this benign event has the potential of progressing to a potentially serious, life-threatening event. Hence, a high index of suspicion is necessary to reach the diagnosis.