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Biomedical subjects

Michael S Kramer

Publications and source records attributed to Michael S Kramer.

At least 55 records · Page 3Linked to original sources

Secular trends of fetal growth in Canada, 1981 to 1997.

Preterm birth and low birthweight in Canada have shown paradoxical temporal trends, with an increase in preterm birth and a decrease in low birthweight. Mean birthweight has increased in many industrialised countries, despite a recent rise in preterm birth, suggesting a temporal increase in fetal growth (birthweight for gestational age) in Canada. We thus described temporal trends in the distribution of fetal growth from 1981 to 1997, including means and proportions of infants at both the low and high ends of the fetal growth distribution. We used data for singleton live births from Statistics Canada's Canadian Birth Data Base for the years 1981-97 (excluding Ontario and Newfoundland) and analysed temporal trends in birthweight and birthweight-for-gestational-age z-score as continuous outcomes and the derived dichotomised outcomes [i.e. low birthweight (<2500 g), very low birthweight (<1500 g), small-for-gestational-age (<10th percentile), very small-for-gestational-age (<3rd percentile), high birthweight (>4000 g), very high birthweight (>4500 g), large-for-gestational-age (>90th percentile), and very large-for-gestational-age (>97th percentile)]. The birthweight-for-gestational-age was based on a newly developed population-based Canadian reference. The results showed that in the overall sample and in a subsample of term and post-term births, mean birthweight, mean z-score, rates of high birthweight, very high birthweight, large-for-gestational-age, and very large-for-gestational-age increased whereas rates of low birthweight, very low birthweight, small-for-gestational-age, and very small-for-gestational-age decreased between 1981-83 and 1995-97. The reverse was observed in preterm births. These temporal changes were larger for more extremely distributed measures of fetal growth. For example, compared with 1981-83, the decrease in 1995-97 for very small-for-gestational-age (<3rd percentile) was 38.9%, whereas the decrease for small-for-gestational-age (<10th percentile) was only 29.7%. Corresponding temporal increases were 21.4% for very large-for-gestational-age (>97th percentile) and 15.2% for large-for-gestational-age (>90th percentile). Among infants with gestational age 34-36 weeks, all measures of fetal growth, including the rates for all dichotomous outcomes, decreased in 1995-97 as compared with 1981-83. We conclude that Canadian infants are getting bigger, but only those born at term. The temporal trends for more extremely distributed fetal growth measures are particularly marked.

Adult↗

Infant growth and health outcomes associated with 3 compared with 6 mo of exclusive breastfeeding.

BACKGROUND: Opinions and recommendations about the optimal duration of exclusive breastfeeding have been strongly divided, but few published studies have provided direct evidence on the relative risks and benefits of different breastfeeding durations in recipient infants. OBJECTIVE: We examined the effects on infant growth and health of 3 compared with 6 mo of exclusive breastfeeding. DESIGN: We conducted an observational cohort study nested within a large randomized trial in Belarus by comparing 2862 infants exclusively breastfed for 3 mo (with continued mixed breastfeeding through >/= 6 mo) with 621 infants who were exclusively breastfed for >/= 6 mo. Regression to the mean, within-cluster correlation, and cluster- and individual-level confounding variables were accounted for by using multilevel regression analyses. RESULTS: From 3 to 6 mo, weight gain was slightly greater in the 3-mo group [difference: 29 g/mo (95% CI: 13, 45 g/mo)], as was length gain [difference: 1.1 mm (0.5, 1.6 mm)], but the 6-mo group had a faster length gain from 9 to 12 mo [difference: 0.9 mm/mo (0.3, 1.5 mm/mo)] and a larger head circumference at 12 mo [difference: 0.19 cm (0.07, 0.31 cm)]. A significant reduction in the incidence density of gastrointestinal infection was observed during the period from 3 to 6 mo in the 6-mo group [adjusted incidence density ratio: 0.35 (0.13, 0.96)], but no significant differences in risk of respiratory infectious outcomes or atopic eczema were apparent. CONCLUSIONS: Exclusive breastfeeding for 6 mo is associated with a lower risk of gastrointestinal infection and no demonstrable adverse health effects in the first year of life.

Adult↗

The epidemiology of adverse pregnancy outcomes: an overview.

This paper provides an overview of the occurrence, etiology and temporal trends of adverse pregnancy outcomes. Disparities between developed and developing countries are highlighted for maternal mortality, infant mortality, stillbirth and low birth weight. The higher rate of low birth weight in developing countries is primarily due to intrauterine growth restriction rather than preterm birth. Much of the excess intrauterine growth restriction is caused by short maternal stature, low prepregnancy body mass index and low gestational weight gain (due to low energy intake). No important contribution has been established for micronutrient intake, nor have different fetal growth trajectories been demonstrated to reflect the timing of exposure to nutritional or other etiologic factors. Infant mortality has declined substantially over time both in developed and developing countries despite no decline (and even an increase) in low birth weight. Several developed countries have reported a temporal increase in fetal growth in infants born at term, a reduction in stillbirth rates and prevention of neural tube defects. More progress is required, however, in understanding the etiology and prevention of preterm birth.

Female↗

Effects of duration and age at onset of type 1 diabetes on preclinical manifestations of nephropathy.

Several studies have reported that the effect of type 1 diabetes disease duration on nephropathy may be greater during or after puberty than an equivalent number of years before puberty. The International Diabetic Nephropathy Study examined the effects of disease duration and age at onset on glomerular morphometry obtained from kidney biopsy in 243 young type 1 diabetic subjects with albumin excretion rates <100 micro g/min: 184 with prepubertal onset, 35 with pubertal onset, and 24 with postpuberty onset. Outcomes included the volume fraction of the glomerulus occupied by the mesangium [Vv(Mes/glom)], glomerular basement membrane (GBM) width, and the surface density of peripheral glomerular capillary basement membrane per glomerulus Sv(PGBM/glom). Vv(Mes/glom) progressed slowly in the first 14 or 15 years after disease onset but more rapidly thereafter. GBM width increased, while Sv(PGBM/glom) decreased with increasing disease duration. No statistically significant differences in the effect of duration were observed among the three age-at-onset subgroups, even with multivariate adjustment for sex, center, baseline HbA(1c) concentration, diastolic blood pressure, height, and BMI. Our results may explain the conflicting results of previous studies regarding the effects of pre-versus postpuberty disease duration.

Adolescent↗

Analysis of perinatal mortality and its components: time for a change?

Since the midtwentieth century, stillbirths (late fetal deaths) and early neonatal deaths have often been combined into a single category of "perinatal" deaths. In the past, such a combination was justified by the fact that asphyxia was a common cause of death during labor (intrapartum stillbirth) and shortly after birth and by geographic and temporal differences in classification of livebirths versus stillbirths. In more recent years, however, the etiologic determinants have diverged sharply, with many fewer early neonatal deaths caused by asphyxia and relatively many more caused by congenital anomalies. Moreover, the increasingly common stratification of pregnancy outcome measures by gestational age or birth weight leads to the use of an inappropriate denominator (total livebirths plus stillbirths within each gestational age or birth weight category) for denoting risk for the stillbirth component, because all unborn fetuses (including the majority of those not born within the specified gestational age or birth weight range) are at risk of being stillborn in that range. The authors suggest that, whenever possible, stillbirths and early neonatal deaths should be reported separately, with gestational age-specific risks of stillbirth based on all fetuses at risk, and that antepartum and intrapartum stillbirths be reported separately.

Adult↗

Relationship of prenatal diagnosis and pregnancy termination to overall infant mortality in Canada.

CONTEXT: Prenatal diagnosis and termination of affected pregnancies can prevent infant deaths due to congenital anomalies, but an effect at the population level has not been shown. OBJECTIVE: To examine the impact of recent changes in congenital anomaly-related fetal and infant deaths on overall population-based infant mortality. DESIGN, SETTING, AND SUBJECTS: Birth cohort-based study of all live births, stillbirths, and infant deaths in Canada (excluding Ontario) for 1991-1998. MAIN OUTCOME MEASURES: Cause-specific infant mortality rates and gestational age-specific fetal death rates. RESULTS: The birth cohort-based infant mortality rate fluctuated between 6.4 and 6.1 per 1000 live births between 1991 and 1995, then dropped to 5.4 per 1000 in 1996 and 5.5 per 1000 in 1997. The rate of infant death from congenital anomalies was stable between 1991 and 1995 but declined by 21% (95% confidence interval, 19%-32%) from 1.86 per 1000 in 1995 to 1.47 per 1000 in 1996 and 1997. Fetal deaths due to pregnancy termination at 20 to 23 weeks' gestation increased dramatically in 1994, while fetal deaths due to congenital anomalies at 20 to 21 weeks increased in 1995 and subsequently. Provinces/territories with high rates of fetal death due to pregnancy termination/congenital anomalies at 20 to 23 weeks had fewer infant deaths due to congenital anomalies. CONCLUSION: A large decrease in infant deaths due to congenital anomalies was associated with the most recent decline in infant mortality in Canada, suggesting that increases in prenatal diagnosis and pregnancy termination for congenital anomalies are related to decreases in overall infant mortality at the population level.

Abortion, Induced↗

Registration artifacts in international comparisons of infant mortality.

Large differences in infant mortality are reported among and within industrialised countries. We hypothesised that these differences are at least partly the result of intercountry differences in registration of infants near the borderline of viability (<750 g birthweight) and/or their classification as stillbirths vs. live births. We used the database of the International Collaborative Effort (ICE) on Perinatal and Infant Mortality to compare infant mortality rates and registration practices in Norway (n = 112484), Sweden (n = 215 908), Israeli Jews (n = 148123), Israeli non-Jews (n = 52 606), US Whites (n = 6 074 222) and US Blacks (n = 1328332). To avoid confounding by strong secular trends in these outcomes, we restricted our analysis to 1987-88, the most recent years for which data are available in the ICE database for all six groups. Compared with Norway (with an infant mortality rate of 8.5 per 1000), the crude relative risks [95% confidence intervals] were 0.75 [0.69,0.81] in Sweden, 0.97 [0.90,1.06] in Israeli Jews, 1.98 [1.81,2.17] in Israeli non-Jews, 0.95 [0.89,1.01] in US Whites and 2.05 [1.95,2.19] in US Blacks. For borderline-viable infants, fetal deaths varied twofold as a proportion of perinatal deaths, with Norway reporting the highest (83.9% for births <500 g and 61.8% for births 500-749 g) and US Blacks the lowest (40.3% and 37.6% respectively) proportions. Reported proportions of live births <500 g varied 50-fold from 0.6 and 0.7 per 10000 in Sweden and Israeli Jews and non-Jews to 9.1 and 33.8 per 10000 in US Whites and Blacks respectively. Reported proportions 500-749 g varied sevenfold from 7.5 per 10000 in Sweden to 16.2 and 55.4 in US Whites and Blacks respectively. After eliminating births <750 g, the relative risks (again with Norway as the reference) of infant mortality changed drastically for US Whites and Blacks: 0.82 [0.76,0.87] and 1.42 [1.33,1.53] respectively. The huge disparities in the ratio of fetal to infant deaths <750 g and in the proportion of live births <750 g among these developed countries probably result from differences in birth and death registration practices. International comparisons and rankings of infant mortality should be interpreted with caution.

Adult↗

Preterm birth, stillbirth and infant mortality among triplet births in Canada, 1985-96.

Recent increases in the frequency of multiple births and simultaneous increases in preterm birth among multiple births have focused attention on such births. However, most previous studies have examined twins rather than higher-order multiples. We carried out a study to examine rates and trends in preterm birth and in gestational age-specific fetal and infant mortality among triplet births in Canada. We used data from the stillbirth, live birth and mortality files of Statistics Canada for the years 1985-97. All births in Canada (excluding those occurring in Ontario and Newfoundland) were included in the study, with two periods (1985-90 vs. 1991-96) being contrasted for assessing temporal change. Changes were estimated using relative risks, 95 confidence intervals [CI] and two-tailed P-values. The rate of preterm birth among triplet live births increased by 6 (95 CI 3, 9) from 90.4 in 1985-90 to 96.0 in 1991-96. Stillbirth rates among triplets did not change significantly and were 30.3 per 1000 total births in 1985-90 and 33.8 per 1000 total births in 1991-96. Infant mortality among triplets declined from 112.7 per 1000 live births in 1985-90 to 73.8 per 1000 live births in 1991-96. In spite of temporal reductions in infant mortality, triplet births continue to be associated with very high rates of preterm birth and fetal and infant mortality. Fetal mortality among triplets has not changed over the last ten years.

Birth Weight↗

Obstetric intervention, stillbirth, and preterm birth.

Despite widespread recognition that preventing preterm birth is the most important perinatal challenge facing industrialized countries, preterm birth has increased steadily in recent years. This article examines the relation between trends in preterm birth, preterm labor induction/cesarean delivery, stillbirth, and infant mortality. The recent rise in preterm birth in the United States and Canada has been mainly due to increases in mild preterm birth (34-36 weeks). Live births at 34 to 36 weeks' gestation have increased largely as a consequence of increases in preterm induction and preterm cesarean delivery among women at high risk for adverse pregnancy outcomes. Increased obstetric intervention at 34 to 36 weeks' gestation appears to have led to larger-than-expected temporal declines in stillbirth rates at this gestation. Infant mortality rates have declined overall and also among live births at 34 to 36 weeks' gestation. Obstetric intervention at preterm gestation, when indicated, can prevent stillbirth and reduce infant morbidity and mortality despite the increasing rates of preterm delivery.

Cesarean Section↗

How does early ultrasound scan estimation of gestational age lead to higher rates of preterm birth?

OBJECTIVE: Early ultrasound scanning estimation of gestational age is known to increase the reported preterm delivery rate (<37 completed weeks) compared with estimation by date of the last normal menstrual period, but it is unclear how this systematic difference arises. STUDY DESIGN: This study was a hospital-based study of 44,623 women who delivered a live-born or stillborn infant between January 1, 1978, and March 31, 1996, and who had both last normal menstrual period-based and early (usually at 16-18 weeks) ultrasound scan-based gestational age estimates. Cross-classification of the 2 estimates by completed weeks was used to examine the direction and magnitude of the differences between them and to compare the resulting classifications of preterm birth. RESULTS: The early ultrasound scan-based gestational age distribution was shifted uniformly to the left (ie, lower gestational age) relative to the last normal menstrual period gestational age distribution; the early ultrasound scan-based preterm delivery rate was 9.1%, which was 19.5% (n = 659 births) higher than the 7.6% rate by last normal menstrual period (P <.0001). The last normal menstrual period estimate exceeded the early ultrasound scan estimate far more often than the reverse, up to and including early ultrasound scan estimates of 40 weeks. No concentration of 4-week discrepancies was observed in either direction, as would be expected with random or systematic errors in recall of the last normal menstrual period. The absolute number of births at 37 to 39 weeks of gestation (by last normal menstrual period) that were reclassified as preterm (n = 1206 births) was much higher than the number of preterm births at 34 to 36 weeks of gestation that were reclassified as term (n = 581 births). The net increase of 625 preterm births (from 581 to 1206 births) that resulted from reclassification of births at 37 to 39 last normal menstrual period weeks accounted for 95% of the total 659-birth increase in early ultrasound scan-based preterm births at all last normal menstrual period gestational ages. CONCLUSION: Early ultrasound scanning reduces the gestational age estimate across the entire gestational age range; early ultrasound scan-based reclassification of gestational age results in a substantial increase in the prevalence of preterm births. Small downward reclassifications exceed upward reclassifications of similar magnitude, which is consistent with previous reports that delayed (>14 days) ovulation is more frequent than early (<14 days) ovulation.

Adult↗

Length of hospital stay, obstetric conditions at childbirth, and maternal readmission: a population-based cohort study.

OBJECTIVE: We assessed the association between obstetric conditions, length of hospital stay for childbirth, and maternal readmission. STUDY DESIGN: A population-based cohort study was conducted on obstetric deliveries (N = 2,652,726) in Canada from 1989 to 1999. Women who were readmitted to the hospital because of obstetric causes within 60 days of initial discharge were identified. RESULTS: Among the readmitted cases, women with cesarean deliveries were more likely to be readmitted to the hospital in the first week after discharge than women with vaginal deliveries (53% vs 41%). After an adjustment for maternal age by means of a Cox regression model, the risk of maternal readmission after cesarean delivery was significantly increased by 21%, 18%, and 10% for mothers with a length of hospital stay of <or=2, 3, and 4 days, respectively, compared with mothers with a length of hospital stay of 5 days. Postpartum hemorrhage, major puerperal infection, and some hypertensive disorders were associated with an elevated risk for maternal readmission and were also the major causes of readmission. CONCLUSION: Short length of hospital stay and several obstetric conditions appear to increase the risk of readmission in women with cesarean birth.

Adolescent↗

Why are babies getting bigger? Temporal trends in fetal growth and its determinants.

OBJECTIVES: To describe temporal trends in fetal "growth" and to examine the roles of sociodemographic, anthropometric, and other determinants. STUDY DESIGN: Hospital-based cohort study of 61,437 nonmalformed singleton live births at 22 to 43 weeks' gestational age. Four main measures were examined: (1) birth weight, (2) birth weight-for-gestational-age Z score, (3) small-for-gestational-age (SGA), and (4) large-for-gestational age (LGA), with the latter 3 measures based on a recently developed population-based Canadian reference. Gestational age was based on the last normal menstrual period if confirmed (+/- 1 week) by early ultrasonogram. RESULTS: The mean birth weight and Z score increased significantly (P <.0001) among infants > or =37 weeks, with a corresponding reduction in % SGA and a rise in % LGA. No consistent trends were seen among births 34 to 36 or < or =33 weeks. When simultaneous changes in maternal prepregnancy body mass index, gestational weight gain, height, cigarette smoking, and other clinical and sociodemographic factors were controlled by using multiple logistic regression, the temporal trends for term infants were no longer evident. CONCLUSIONS: Increases in maternal anthropometry, reduced cigarette smoking, and changes in sociodemographic factors have led to an increase in the weight of infants born at or after term.

Adolescent↗

Reduction of cerebral infarction using the third circulation.

OBJECTIVE: To ascertain whether ventriculosubarachnoid perfusion of the brain with an oxygen-carrying nutrient emulsion affects the volume of infarction in animals with permanent middle cerebral artery occlusion. DESIGN: Prospective, randomized, controlled trial. SETTING: An animal laboratory in a university setting. SUBJECTS: Twenty-eight closed colony adult cats weighing between 3.5 and 4.5 kg. INTERVENTIONS: Cats were assigned randomly into one of three groups: untreated surgical controls, artificial cerebrospinal fluid (ACSF) perfused, or oxygenated fluorochemical (t-bis perfluorobutylethylene; F44E) nutrient emulsion (OFNE) perfused. The formulation used in this study was developed for clinical use and is currently being used in a phase 1 clinical trial in patients with severe ischemic stroke. Focal cerebral ischemia was induced by permanently clipping the middle cerebral artery via the retro-orbital approach. Treatment was initiated 90 mins postocclusion and continued for 18 hrs. Animals were killed 1 hr after the termination of perfusion, the brains were sectioned and stained with 2,3,5-triphenyltetrazolium chloride, and the infarct area was determined with a computer digitizer. MEASUREMENTS AND MAIN RESULTS: There was a significant difference in cerebral infarct volume in the OFNE-perfused animals compared with the other groups ( p<or=.015). Intracranial pressure was significantly reduced in the OFNE-perfused group relative to the surgical control group at 18 hrs ( P<or=.05). Overall, infarct volume correlated with intracranial pressure measured at the end of the treatment period (Spearman rank order, p<.001). CONCLUSIONS: Fluorochemical emulsion delivery of oxygen and nutrients directly to the brain by means of ventriculocisternal perfusion is a viable treatment alternative for cerebral ischemia. In addition, this technique may control elevations in intracranial pressure following stroke.

Analysis of Variance↗

Algorithms for combining menstrual and ultrasound estimates of gestational age: consequences for rates of preterm and postterm birth.

We compared rates of preterm and postterm birth according to six algorithms for gestational age (GA) estimates based on last menstrual period (LMP) and early ultrasound (EUS): LMP alone, LMP if the discrepancy between the two estimates was within 14 days and otherwise EUS (14-day rule), a 10-day rule, a seven-day rule, a three-day rule and EUS alone. In a sample of 44,623 births in a Canadian tertiary hospital, the choice of algorithms makes a substantial impact on both preterm and postterm birth rates, even when EUS was used for discrepancies over two weeks.

Algorithms↗

Breastfeeding and infant growth: biology or bias?

BACKGROUND: Available evidence suggests that prolonged and exclusive breastfeeding is associated with lower infant weight and length by 6 to 12 months of age. This evidence, however, is based on observational studies, which are unable to separate the effects of feeding mode per se from selection bias, reverse causality, and the confounding effects of maternal attitudinal factors. DESIGN/METHODS: A cluster-randomized trial in the Republic of Belarus of a breastfeeding promotion intervention modeled on the World Health Organization (WHO)/UNICEF Baby-Friendly Hospital Initiative versus control (then current) infant feeding practices. Healthy, full-term, singleton breastfed infants (n = 17 046) weighing > or =2500 g were enrolled soon after birth and followed up at 1, 2, 3, 6, 9, and 12 months old for measurements of weight, length, and head circumference. Data were analyzed according to intention-to-treat, while accounting for within-cluster correlation. To assess the potential for bias in observational studies of breastfeeding, we also analyzed our data as if we had conducted an observational study by ignoring treatment, combining the 2 randomized groups, and comparing 1378 infants weaned in the first month and those breastfed for the full 12 months of follow-up with either > or =3 months (n = 1271) or > or =6 months (n = 251) of exclusive breastfeeding. RESULTS: Infants from the experimental sites were significantly more likely to be breastfed (to any degree) at 3, 6, 9, and 12 months and were far more likely to be exclusively breastfed at 3 months (43.3% vs 6.4%). Mean birth weight was nearly identical in the 2 groups (3448 g, experimental; 3446 g, control). Mean weight was significantly higher in the experimental group by 1 month of age (4341 vs 4280 g). The difference increased through 3 months (6153 g vs 6047 g), declined slowly thereafter, and disappeared by 12 months (10564 g vs 10571 g). Analysis by z scores confirmed that infants in both groups gained more weight than the WHO/Centers for Disease Control and Prevention reference, with no evidence of undernutrition in the control group. Length followed a similar pattern. In the observational analyses, infants weaned in the first month were slightly lighter and shorter at birth and their weight-for-age and length-for-age z scores declined by 1 month, but they caught up to both experimental and the other observational groups by 6 months and were heavier and longer by 12 months. Among infants in the 2 prolonged and exclusive breastfeeding groups, weight-for-age z scores fell slightly between 3 and 12 months; length-for-age fell below the reference by 6 months with catch-up to the reference by 12 months. Head circumference showed no significant differences at any age between the 2 trial groups or among the observational groups. CONCLUSIONS: Our data, the first in humans based on a randomized experiment, suggest that prolonged and exclusive breastfeeding may actually accelerate weight and length gain in the first few months, with no detectable deficit by 12 months old. These results add support to current WHO and UNICEF feeding recommendations. Our observational analysis showing faster weight and length gains with early weaning and slower gains with prolonged and exclusive breastfeeding may reflect unmeasured confounding differences or a true biological effect of formula feeding.

Breast Feeding↗

The impact of the increasing number of multiple births on the rates of preterm birth and low birthweight: an international study.

OBJECTIVES: We studied the effects of twins and triplets on perinatal health indicators in the overall population in the 1980s and 1990s in Canada, England and Wales, France, and the United States. METHODS: Data were derived mostly from live birth registration. We used rates, relative risks, and population attributable risks for twins and triplets separately. RESULTS: In each country, the increase in multiple births, and the increase in preterm delivery among multiple births, contributed almost equally to the rise in or stabilization of the overall rates of preterm delivery. Twins contributed a much larger proportion of the preterm deliveries and low-birthweight newborns than did triplets. CONCLUSIONS: Twins have a major population-based impact on the trends of perinatal health indicators.

Canada↗