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1.  Perinatal outcomes in a South Asian setting with high rates of low birth weight 
It is unclear whether the high rates of low birth weight in South Asia are due to poor fetal growth or short pregnancy duration. Also, it is not known whether the traditional focus on preventing low birth weight has been successful. We addressed these and related issues by studying births in Kaniyambadi, South India, with births from Nova Scotia, Canada serving as a reference.
Population-based data for 1986 to 2005 were obtained from the birth database of the Community Health and Development program in Kaniyambadi and from the Nova Scotia Atlee Perinatal Database. Menstrual dates were used to obtain comparable information on gestational age. Small-for-gestational age (SGA) live births were identified using both a recent Canadian and an older Indian fetal growth standard.
The low birth weight and preterm birth rates were 17.0% versus 5.5% and 12.3% versus 6.9% in Kaniyambadi and Nova Scotia, respectively. SGA rates were 46.9% in Kaniyambadi and 7.5% in Nova Scotia when the Canadian fetal growth standard was used to define SGA and 6.7% in Kaniyambadi and < 1% in Nova Scotia when the Indian standard was used. In Kaniyambadi, low birth weight, preterm birth and perinatal mortality rates did not decrease between 1990 and 2005. SGA rates in Kaniyambadi declined significantly when SGA was based on the Indian standard but not when it was based on the Canadian standard. Maternal mortality rates fell by 85% (95% confidence interval 57% to 95%) in Kaniyambadi between 1986–90 and 2001–05. Perinatal mortality rates were 11.7 and 2.6 per 1,000 total births and cesarean delivery rates were 6.0% and 20.9% among live births ≥ 2,500 g in Kaniyambadi and Nova Scotia, respectively.
High rates of fetal growth restriction and relatively high rates of preterm birth are responsible for the high rates of low birth weight in South Asia. Increased emphasis is required on health services that address the morbidity and mortality in all birth weight categories.
PMCID: PMC2647522  PMID: 19203384
2.  The fetuses-at-risk approach: Clarification of semantic and conceptual misapprehension 
Although proponents of the fetuses-at-risk approach describe it as a causal model that resolves various conundrums, several areas of semantic and conceptual misapprehension remain. Differences in terminology include use of denominators such as 'ongoing pregnancies' and the need for an ad hoc 'correction factor' in order to calculate gestational age-specific rates. Further, there is conceptual disagreement regarding the proper candidates for neonatal death and related phenomena. Perhaps the most egregious misconception is the belief that rising rates of gestational age-specific perinatal mortality observed under the fetuses-at-risk model automatically imply the need for indiscriminate increases in iatrogenic preterm delivery.
The term 'fetuses at risk' addresses the plurality of candidates for stillbirth in a multi-fetal pregnancy, while the use of standard terminology such as 'cumulative incidence' and 'incidence density' harmonizes the language of perinatal epidemiology with that used in the general epidemiologic literature. On the conceptual side, it is necessary to integrate clinical insights regarding latent periods into models of neonatal morbidity and mortality. The contention that the fetuses-at-risk approach implies the need for indiscriminate iatrogenic preterm delivery is a non-sequitur (just as rising age-specific cancer death rates do not imply the need for routine chemotherapy and radiation for all middle aged people). Finally, the traditional and fetuses-at-risk models are better viewed in terms of function as prognostic (non-causal) and causal models, respectively.
A careful examination of terms and concepts helps situate the traditional perinatal and the fetuses-at-risk approaches within the broader context of non-causal and causal models within general epidemiology.
PMCID: PMC2292135  PMID: 18366767
3.  Theory of obstetrics: An epidemiologic framework for justifying medically indicated early delivery 
Modern obstetrics is faced with a serious paradox. Obstetric practice is becoming increasingly interventionist based on empirical evidence but without a theoretical basis for such intervention. Whereas obstetric models of perinatal death show that mortality declines exponentially with increasing gestational duration, temporal increases in medically indicated labour induction and cesarean delivery have resulted in rising rates of preterm birth and declining rates of postterm birth. Other problems include a disconnection between patterns of gestational age-specific growth restriction (constant across gestation) and gestational age-specific perinatal mortality (exponential decline with increasing duration) and the paradox of intersecting perinatal mortality curves (low birth weight infants of smokers have lower neonatal mortality rates than the low birth weight infants of non-smokers).
The fetuses at risk approach is a causal model that brings coherence to the various perinatal phenomena. Under this formulation, pregnancy complications (such as preeclampsia), labour induction/cesarean delivery, birth, revealed small-for-gestational age and death show coherent patterns of incidence. The fetuses at risk formulation also provides a theoretical justification for medically indicated early delivery, the cornerstone of modern obstetrics. It permits a conceptualization of the number needed to treat (e.g., as low as 2 for emergency cesarean delivery in preventing perinatal death given placental abruption and fetal bradycardia) and a calculation of the marginal number needed to treat (i.e., the number of additional medically indicated labour inductions/cesarean deliveries required to prevent one perinatal death). Data from the United States showed that between 1995–96 and 1999–2000 rates of labour induction/cesarean delivery increased by 45.1 per 1,000 and perinatal mortality decreased by 0.31 per 1,000 total births among singleton pregnancies at > = 28 weeks of gestation. The marginal number needed to treat was 145 (45.1/0.31), showing that 145 excess labour inductions/cesarean deliveries in 1999–2000 (relative to 1995–96) were responsible for preventing 1 perinatal death among singleton pregnancies at > = 28 weeks gestation.
The fetuses at risk approach, with its focus on incidence measures, provides a coherent view of perinatal phenomena. It also provides a theoretical justification for medically indicated early delivery and reconciles the contemporary divide between obstetric theory and obstetric practice.
PMCID: PMC1851971  PMID: 17391525
4.  Study protocol: a double blind placebo controlled trial examining the effect of domperidone on the composition of breast milk [NCT00308334] 
Domperidone, a drug that enhances upper gastric motility, is an anti-dopaminergic medication that also elevates prolactin levels. It has been shown to safely increase the milk supply of lactating women. To date, researchers have analyzed the effects of domperidone on lactating woman with respect to the quantity of their milk production, adverse effects, and drug levels in the breast milk. However, the effect of domperidone on the macronutrient composition of breast milk has not been studied and current guidelines for fortification of human milk for premature infants do not distinguish between those women using or those not using domperidone. The purpose of this study is to evaluate the effect of domperidone (given to lactating mothers of very preterm infants) on the macronutrient composition of breast milk.
Mothers of infants delivered at less than 31 weeks gestation, who are at least 3 weeks postpartum, and experiencing lactational failure despite non-pharmacological interventions, will be randomized to receive domperidone (10 mg three times daily) or placebo for a 14-day period.
Breast milk samples will be obtained the day prior to beginning treatment and on days 4, 7 and 14. The macronutrient (protein, fat, carbohydrate and energy) and macromineral content (calcium, phosphorus and sodium) will be analyzed and compared between the two groups. Additional outcome measures will include milk volumes, serum prolactin levels (measured on days 0, 4, and 10), daily infant weights and breastfeeding rates at 2 weeks post study completion and at discharge. Forty-four participants will be recruited into the study. Analysis will be carried out using the intention to treat approach.
If domperidone causes significant changes to the nutrient content of breast milk, an alteration in feeding practices for preterm infants may need to be made in order to optimize growth, nutrition and neurodevelopment outcomes.
PMCID: PMC1562444  PMID: 16719919
5.  Customized birth weight for gestational age standards: Perinatal mortality patterns are consistent with separate standards for males and females but not for blacks and whites 
Some currently available birth weight for gestational age standards are customized but others are not. We carried out a study to provide empirical justification for customizing such standards by sex and for whites and blacks in the United States.
We studied all male and female singleton live births and stillbirths (22 or more weeks of gestation; 500 g birth weight or over) in the United States in 1997 and 1998. White and black singleton live births and stillbirths were also examined. Qualitative congruence between gestational age-specific growth restriction and perinatal mortality rates was used as the criterion for identifying the preferred standard.
The fetuses at risk approach showed that males had higher perinatal mortality rates at all gestational ages compared with females. Gestational age-specific growth restriction rates based on a sex-specific standard were qualitatively consistent with gestational age-specific perinatal mortality rates among males and females. However, growth restriction patterns among males and females based on a unisex standard could not be reconciled with perinatal mortality patterns. Use of a single standard for whites and blacks resulted in gestational age-specific growth restriction rates that were qualitatively congruent with patterns of perinatal mortality, while use of separate race-specific standards led to growth restriction patterns that were incompatible with patterns of perinatal mortality.
Qualitative congruence between growth restriction and perinatal mortality patterns provides an outcome-based justification for sex-specific birth weight for gestational age standards but not for the available race-specific standards for blacks and whites in the United States.
PMCID: PMC551609  PMID: 15720720
6.  A parsimonious explanation for intersecting perinatal mortality curves: understanding the effects of race and of maternal smoking 
Neonatal mortality rates among black infants are lower than neonatal mortality rates among white infants at birth weights <3000 g, whereas white infants have a survival advantage at higher birth weights. This finding is also observed when birth weight-specific neonatal mortality rates are compared between infants of smokers and non-smokers. We provide a parsimonious explanation for this paradoxical phenomenon.
We used data on births in the United States in 1997 after excluding those with a birth weight <500 g or a gestational age <22 weeks. Birth weight- and gestational age-specific perinatal mortality rates were calculated per convention (using total live births at each birth weight/gestational age as the denominator) and also using the fetuses at risk of death at each gestational age.
Perinatal mortality rates (calculated per convention) were lower among blacks than whites at lower birth weights and at preterm gestational ages, while blacks had higher mortality rates at higher birth weights and later gestational ages. With the fetuses-at-risk approach, mortality curves did not intersect; blacks had higher mortality rates at all gestational ages. Increases in birth rates and (especially) growth-restriction rates presaged gestational age-dependent increases in perinatal mortality. Similar findings were obtained in comparisons of smokers versus nonsmokers.
Formulating perinatal risk based on the fetuses-at-risk approach solves the intersecting perinatal mortality curves paradox; blacks have higher perinatal mortality rates than whites and smokers have higher perinatal mortality rates than nonsmokers at all gestational ages and birth weights.
PMCID: PMC419704  PMID: 15090071
7.  Does the risk of cerebral palsy increase or decrease with increasing gestational age? 
It is generally accepted that the risk of cerebral palsy decreases with increasing gestational age of live born infants. However, recent studies have shown that cerebral palsy often has prenatal antecedents including congenital malformations, vascular insults and maternal infection. Cerebral palsy is therefore better viewed as occurring among fetuses, rather than among infants. We explored the epidemiologic implications of this change in perspective.
We used recently published data from Shiga Prefecture, Japan and from North-East England to examine the pattern of gestational age-specific rates of cerebral palsy under these alternative perspectives. We first calculated gestational age-specific rates of cerebral palsy as per convention, by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of live births in that gestational age category. Under the alternative formulation, we calculated gestational age-specific rates of cerebral palsy by dividing the number of cases of cerebral palsy identified among live births within any gestational age category by the number of fetuses who were at risk of being born at that gestation and being afflicted with cerebral palsy.
Under the conventional formulation, cerebral palsy rates decreased with increasing gestational age from 63.9 per 1,000 live births at <28 weeks gestation to 0.9 per 1,000 live births at 37 or more weeks gestation. When fetuses were viewed as potential candidates for cerebral palsy, cerebral palsy rates increased with increasing gestational age from 0.08 per 1,000 fetuses at risk at <28 weeks gestation to 0.9 per 1,000 fetuses at risk at 37 or more weeks gestation.
The fetuses-at-risk approach is the appropriate epidemiologic formulation for calculating the gestational age-specific rate of cerebral palsy from a causal perspective. It shows that the risk of cerebral palsy increases as gestational duration increases. This compelling view of cerebral palsy risk may help refocus research aimed at understanding and preventing cerebral palsy.
PMCID: PMC317470  PMID: 14693037

Results 1-7 (7)