Robert H. Usher

Increased Maternal Age and the Risk of Fetal Death

BACKGROUND Although the fetal death rate has declined over the past 30 years among women of all ages, it is unknown whether particular characteristics of the mother, such as age, still affect the risk of fetal death. We undertook a study to determine whether older age, having a first child (nulliparity), or other characteristics of the mother are risk factors for fetal death. METHODS We used data from the McGill Obstetrical Neonatal Database to evaluate risk factors for fetal death among all deliveries at the Royal Victoria Hospital in Montreal (n = 94,346) from 1961 through 1993. Data were available for two time periods (1961 through 1974 and 1978 through 1993); data for 1975 through 1977 have not been entered into the data base and were therefore not included. Using logistic regression, we estimated the effect of specific maternal characteristics and complications of pregnancy on the risk of fetal death. RESULTS The fetal death rate decreased significantly from 11.5 per 1000 total births (including live births and stillbirths) in the 1960s to 3.2 per 1000 in 1990 through 1993 (P < 0.001). Between these periods, the average maternal age at delivery increased from 27 to 30 years (P < 0.001), and the frequency of the diagnosis of diabetes and hypertension during pregnancy increased fivefold (P < 0.001). Nevertheless, after we controlled for these and other maternal characteristics, women 35 years of age or older continued to have a significantly higher rate of fetal death than their younger counterparts (odds ratio for women 35 to 39 years of age as compared with women < 30 years of age, 1.9; 95 percent confidence interval, 1.3 to 2.7; for those 40 or older, 2.4; 95 percent confidence interval, 1.3 to 4.5). CONCLUSIONS Changes in maternal health and obstetrical practice have resulted in a 70 percent decline in the rate of fetal death among pregnant women of all ages since the 1960s. Advancing maternal age, however, continues to be a risk factor for fetal death.

Very Low Birth Weight: A Problematic Cohort for Epidemiologic Studies of Very Small or Immature Neonates

Despite widespread acceptance of the concept of very low birth weight (VLBW), i.e., birth weight of less than or equal to 1,500 g, VLBW infants represent an extremely heterogeneous group of newborns, including those with very immature gestational age and those who are more mature but extremely growth retarded. To demonstrate how use of the VLBW rubric can lead to confounding bias that is not only large in magnitude but impossible to control satisfactorily, the authors divided 640 consecutive live neonates born in the Royal Victoria Hospital, Montreal, Canada, from 1978 to 1987 into two overlapping groups: a VLBW cohort (birth weight, 500-1500 g; n = 573) and a gestational age cohort (gestational age, 23-30 completed weeks; n = 466). Variation in growth status by gestational age was much more uniform in the 23- to 30-week cohort. Thus, although mean birth weight was similar in the 500- to 1,500-g and 23- to 30-week cohorts (1,055 vs. 1,064 g), the 500- to 1,500-g cohort was more mature (mean gestational age, 28.8 vs. 27.8 weeks; upper range, 39.7 vs. 30.9 weeks) and had twice the rate of intrauterine growth retardation (25.7 vs. 11.5%). These differences in maturity and growth resulted in a misleading protective effect of intrauterine growth retardation against in-hospital death in the 500- to 1,500-g cohort (crude odds ratio = 0.55 (95% confidence interval 0.36-0.83] and a greater discrepancy in maturity between cesarean- and vaginally delivered infants (3.1 vs. 1.5 weeks) in the 500- to 1,500-g vs. 23- to 30-week cohorts. These differences arise from inextricable confounding of growth status and maturity in the 500- to 1,500-g cohort, the most mature infants also being the most growth retarded. The removal of well-grown infants with birth weights of greater than 1,500 g from the VLBW cohort leads to a progressively distorted spectrum of growth with advancing gestational age and an artifactual blunting of the beneficial effects of increasing maturity. The authors suggest that whenever fetal growth is an important exposure, outcome, or confounding variable, epidemiologic studies of extremely small or immature newborns should be based on gestational age rather than the VLBW criterion.

Fetal malnutrition: Its incidence, causes, and effects☆

F 33 T A L G R 0 W T H in UierO iS a fUnCtiOn of both seed and soil. It is dependent upon the growth potential of the fetus and the availability of intrauterine nutrition, in its broadest sense, to fulfill this potential. The result of these two factors is a wide distribution of birth size at any one gestational age, and a wide variation in the state of nutrition at birth. The concept that clinically significant malnutrition can occur in utero associated with intrauterine asphyxia was deveIoped by Clifford* to explain fetal distress in utero and clinical evidence of soft tissue wasting at birth in infants who were delivered after term. He attributed these to decreasing placental function with advancing maturity. Intrauterine malnutrition has been recognized to occur in other circumstances, and to play a significant role in perinatal pathology. It has been implicated as a cause of stillbirth,z anomalies,3 neonatal hypoglycemia,41 5 and permanent physical and possibly mental retardation.3 The condition has been attributed to maternal diseases,6 toxemia of pregnancy,’ and placental pathology,* in addition to postmaturity. For the majority of cases, however, no specific cause is apparent. Existing terminology for intrauterine mal-

Obstetric outcomes and congenital abnormalities after in vitro maturation, in vitro fertilization, and intracytoplasmic sperm injection.

OBJECTIVE: To compare obstetric outcome and congenital abnormalities in pregnancies conceived after in vitro maturation (IVM), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) with those in spontaneously conceived controls. METHODS: Data were collected from the McGill Obstetrics and Neonatal Database (MOND). All children were examined and classified in a standard manner. Final data were reviewed 12 months after delivery. Pregnancies by IVM, IVF, and ICSI were compared with those of age- and parity-matched controls. Congenital abnormality, gestational age, birth weight, Apgar scores, cord pH, growth restriction, pregnancy complications, mode of delivery, and multiple pregnancy were compared. RESULTS: A total of 432 children were born from 344 pregnancies after assisted reproductive technology (ART) during the study period (IVM 55, IVF 217, ICSI 160). The observed odds ratios (ORs) for any congenital abnormality were 1.42 (95% confidence interval [CI] 0.52–3.91) for IVM, 1.21 (95% CI 0.63–2.62) for IVF, and 1.69 (95% CI 0.88–3.26) for ICSI. Twin pregnancy (IVM 21%, IVF 20%, ICSI 17%) and triplet pregnancy (IVM 5%, IVF 3%, ICSI 3%) were higher than those in controls (1.7% twins and 0% triplets) (P<.001). Cesarean delivery rates were higher after ART, even in singleton pregnancies (IVM 39%, IVF 36%, ICSI 36%; controls: 26.3%) (P<.05). Apgar scores, cord pH, growth restriction, and pregnancy complications were comparable in all groups. CONCLUSION: All ART pregnancies are associated with an increased risk of multiple pregnancy, cesarean delivery, and congenital abnormality. Compared with IVF and ICSI, IVM is not associated with any additional risk. LEVEL OF EVIDENCE: II

Risk of respiratory distress syndrome related to gestational age, route of delivery, and maternal diabetes.

Abstract From this analysis, respiratory distress syndrome appears to be a condition related to prematurity, exacerbated by cesarean section delivery, and unaffected by maternal diabetes. The incidence and mortality rate are inversely related to gestational age with the syndrome probably rarely, if ever, occurring after 38 weeks. Cesarean section is associated with a markedly increased incidence and mortality rate. The incidence of respiratory distress syndrome in infants of diabetic mothers is the same as in infants of nondiabetic mothers when delivered at the same gestational age and by the same route. When premature delivery is considered for maternal or fetal complications, it should, whenever possible, be effected vaginally rather than by cesarean section.

Etiologic determinants of abruptio placentae

Objective To quantify the roles of suspected sociodemographic, anthropometric, behavioral, and pathologic determinants in the etiology of abruptio placentae. Methods We performed a hospital-based cohort study of 36,875 nonreferred births January 1978 and March 1989. Gestational age was based on menstrual dates confirmed (within 7 days) by early ultrasound. Results Parity, maternal education, pre-pregancy weight, and the rate of net gestational weight gain did not have significant independent associations with abruption. Significant determinants included the following: severe small for gestational-age (SGA) birth (odds ratio [OR] 3.99; 95% confidence interval [CI] 2.75, 5.77), chorioamnionitis (OR 2.50; 95% CI 1.58, 3.98), prolonged rupture of membranes (OR 2.38; 95% CI 1.55, 3.65), preeclampsia (OR 2.05; 95% CI 1.39, 3.04), pregnancy-induced hypertension without albuminuria (OR 1.57; 95% CI 1.00, 2.46), pre-pregnancy hypertension (OR 1.77; 95% CI 1.05, 2.99), maternal age at least 35 years (OR 1.50; 95% CI 1.14, 2.01), unmarried status (OR 1.50; 95% CI 1.13, 1.98), cigarette smoking (OR 1.40; 95% CI 1.00, 1.97 for ten to 19 cigatettes per day and OR 1.13; 95% CI 0.81, 1.59 for at least 20 cigarettes per day), and male fetal gender (OR 1.38; 95% CI 1.12, 1.70). Removal of SGA from the regression model resulted in little change in the magnitude of the other associations. Conclusions Severe fetal growth restriction, prolonged rupture of membranes, chorioamnionitis, hypertension (before pregnancy and pregnancy-induced), cigarette smoking, advanced maternal age, unmarried status, and male fetal gender are significant etiologic determinants of placental abruption. Non-SGA determinants appear to operate largely independently of their effects on fetal growth.

Assessment of fetal risk in postdate pregnancies

To assess postdate fetal risk, pregnancies in which menstrual history was confirmed by early ultrasound examination were reviewed; 5915 pregnancies within 1 week of term, 1408 1 to 2 weeks postdate, and 340 at least 2 weeks postdate. Fetal distress and meconium release were twice as frequent and meconium aspiration eight times as frequent postterm. Birth asphyxia was unrelated to gestational age. Fractures and palsies were more frequent because of primiparity and macrosomia. Only one antepartum fetal death occurred in 1748 postdate pregnancies. Review of 674 perinatal deaths at 37 plus weeks in Quebec showed no increase in deaths postterm. The increase in fetal distress and meconium aspiration postterm without an increase in birth asphyxia or fetal death may reflect greater responsiveness of the more mature fetus to mild asphyxic insults. Findings of this study could not justify increased fetal monitoring in postdate pregnancies.

Terminal digit preference, random error, and bias in routine clinical measurement of blood pressure

We examined the presence, magnitude, and consequences of systematic and random errors caused by terminal digit preference in the measurement of highest systolic blood pressure during prenatal visits in 28,841 non-referred pregnant women who delivered between 1 January 1982 and 31 March 1990. In the overall distribution of terminal digit readings, 78% were read to 0, 15% to even digits other than 0, 5% to 5, and only 2% to odd digits other than 5. This preference for 0s was consistent across the entire distribution of blood pressure and for a variety of maternal characteristics. The relative frequency of the cutoff value of 140 mmHg (i.e. the percentage of readings on 140 mmHg) within the range containing the value (i.e. 138-142 mmHg) was similar to the relative frequency of other multiples of 0. This was true whether the comparison was made in the overall study sample, or in a pre-selected low-risk subgroup or high-risk subgroup, indicating no systematic bias. On the other hand, a strong tendency to read blood pressure values to the nearest 0 had a marked effect on the classification of hypertension. Changing the definition of hypertension from > or = 140 mmHg to > 140 mmHg produced a reduction in prevalence of hypertension from 25.9 to 13.3% in the overall study sample, from 15.4 to 6.3% in the low-risk subgroup, and from 43.3 to 25.3% in the high-risk subgroup. Epidemiologic studies that compare prevalences of hypertension in different populations based on routine clinical measurement of blood pressure and a single cutoff point should assess the consequences of terminal digit preference in defining hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Causes of fetal death in women of advanced maternal age

Objective To examine which causes of fetal death occur more often in older women and to determine whether these causes have changed significantly since the 1960s and early 1970s. Methods Data from the McGill Obstetrical Neonatal Database were used to calculate rates of specific causes of fetal death in women younger than 35 and in women 35 years or older. Among the 101,640 births between 1961 and 1995, there were 715 stillbirths and 822 neonatal deaths. The autopsy rate was 97% and categorization of the causes of fetal death remained consistent over this 34-year period. The rates of specific causes of fetal death per 10,000 total births were determined for an earlier period (1961–1974) and a later period (1978–1995). Results Compared with the 1961–1974 period, there was a 60% reduction in the rates of both fetal and neonatal deaths during 1978–1995 (P < .001). During 1961–1974, women 35 years or older were more likely than their younger counter-parts to have fetal death due to lethal congenital anomalies (odds ratio [OR] 3.2; 95% confidence interval [CI] 1.5, 6.5); this was no longer true in the 1978–1995 period. From 1978 to 1995, older women were at a statistically significant increased risk for “unexplained” fetal death (OR 2.2; 95% CI 1.3, 3.8); women 35 years of age or older had approximately one in 440 births end in unexplained fetal death, compared to one in 1000 births for women younger than 35. Conclusions Advanced maternal age is no longer associated with an increased risk for fetal death due to congenital anomalies. However, older women have a significantly higher risk for unexplained fetal death. The identification of those maternal and fetal characteristics that contribute to unexplained fetal death and its prevention remain important challenges for contemporary obstetric practice.

Has an increased cesarean section rate for term breech delivery reduced the incidence of birth asphyxia, trauma, and death?

To evaluate whether the dramatic rise in the cesarean section rate for breech presentation (from 22% in the decade 1963 to 1973 to 94% in 1978 and 1979) has been justified, 770 term breech deliveries at the Royal Victoria Hospital during the period 1963 to 1973 and during 1978 and 1979 have been reviewed. Neonatal outcome, as determined by one neonatologist during the entire period of this study, was analyzed according to vaginal or cesarean section breech deliveries of primiparous and multiparous women. For each method of delivery and state of parity the occurrence of asphyxia neonatorum, abnormal cerebral signs, postasphyctic congenital heart failure or renal failure, and intrapartum and neonatal deaths was studied. The most severe cases were individually reviewed. While breech presentation has become a virtual indication for cesarean section in many centers, to date , there has not been an evaluation of how effective this procedure is in reducing birth asphyxia and trauma. In this study we assessed whether the trend to perform cesarean section in all term breech presentations is justified and whether neonatal morbidity and mortality rates have actually improved as a result.