Saroj Saigal

An overview of mortality and sequelae of preterm birth from infancy to adulthood.

Survival rates have greatly improved in recent years for infants of borderline viability; however, these infants remain at risk of developing a wide array of complications, not only in the neonatal unit, but also in the long term. Morbidity is inversely related to gestational age; however, there is no gestational age, including term, that is wholly exempt. Neurodevelopmental disabilities and recurrent health problems take a toll in early childhood. Subsequently hidden disabilities such as school difficulties and behavioural problems become apparent and persist into adolescence. Reassuringly, however, most children born very preterm adjust remarkably well during their transition into adulthood. Because mortality rates have fallen, the focus for perinatal interventions is to develop strategies to reduce long-term morbidity, especially the prevention of brain injury and abnormal brain development. In addition, follow-up to middle age and beyond is warranted to identify the risks, especially for cardiovascular and metabolic disorders that are likely to be experienced by preterm survivors.

Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial

BACKGROUND For 3-4% of pregnancies, the fetus will be in the breech presentation at term. For most of these women, the approach to delivery is controversial. We did a randomised trial to compare a policy of planned caesarean section with a policy of planned vaginal birth for selected breech-presentation pregnancies. METHODS At 121 centres in 26 countries, 2088 women with a singleton fetus in a frank or complete breech presentation were randomly assigned planned caesarean section or planned vaginal birth. Women having a vaginal breech delivery had an experienced clinician at the birth. Mothers and infants were followed-up to 6 weeks post partum. The primary outcomes were perinatal mortality, neonatal mortality, or serious neonatal morbidity; and maternal mortality or serious maternal morbidity. Analysis was by intention to treat. FINDINGS Data were received for 2083 women. Of the 1041 women assigned planned caesarean section, 941 (90.4%) were delivered by caesarean section. Of the 1042 women assigned planned vaginal birth, 591 (56.7%) delivered vaginally. Perinatal mortality, neonatal mortality, or serious neonatal morbidity was significantly lower for the planned caesarean section group than for the planned vaginal birth group (17 of 1039 [1.6%] vs 52 of 1039 [5.0%]; relative risk 0.33 [95% CI 0.19-0.56]; p<0.0001). There were no differences between groups in terms of maternal mortality or serious maternal morbidity (41 of 1041 [3.9%] vs 33 of 1042 [3.2%]; 1.24 [0.79-1.95]; p=0.35). INTERPRETATION Planned caesarean section is better than planned vaginal birth for the term fetus in the breech presentation; serious maternal complications are similar between the groups.

Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants.

BACKGROUND The prophylactic administration of indomethacin reduces the frequency of patent ductus arteriosus and severe intraventricular hemorrhage in very-low-birth-weight infants (those with birth weights below 1500 g). Whether prophylaxis with indomethacin confers any long-term benefits that outweigh the risks of drug-induced reductions in renal, intestinal, and cerebral blood flow is not known. METHODS Soon after they were born, we randomly assigned 1202 infants with birth weights of 500 to 999 g (extremely low birth weight) to receive either indomethacin (0.1 mg per kilogram of body weight) or placebo intravenously once daily for three days. The primary outcome was a composite of death, cerebral palsy, cognitive delay, deafness, and blindness at a corrected age of 18 months. Secondary long-term outcomes were hydrocephalus necessitating the placement of a shunt, seizure disorder, and microcephaly within the same time frame. Secondary short-term outcomes were patent ductus arteriosus, pulmonary hemorrhage, chronic lung disease, ultrasonographic evidence of intracranial abnormalities, necrotizing enterocolitis, and retinopathy. RESULTS Of the 574 infants with data on the primary outcome who were assigned to prophylaxis with indomethacin, 271 (47 percent) died or survived with impairments, as compared with 261 of the 569 infants (46 percent) assigned to placebo (odds ratio, 1.1; 95 percent confidence interval, 0.8 to 1.4; P=0.61). Indomethacin reduced the incidence of patent ductus arteriosus (24 percent vs. 50 percent in the placebo group; odds ratio, 0.3; P<0.001) and of severe periventricular and intraventricular hemorrhage (9 percent vs. 13 percent in the placebo group; odds ratio, 0.6; P=0.02). No other outcomes were altered by the prophylactic administration of indomethacin. CONCLUSIONS In extremely-low-birth-weight infants, prophylaxis with indomethacin does not improve the rate of survival without neurosensory impairment at 18 months, despite the fact that it reduces the frequency of patent ductus arteriosus and severe periventricular and intraventricular hemorrhage.

Behavioural problems in children who weigh 1000 g or less at birth in four countries.

BACKGROUND The increased survival chances of extremely low-birthweight (ELBW) infants (weighing <1000 g at birth) has led to concern about their behavioural outcome in childhood. In reports from several countries with different assessments at various ages, investigators have noted a higher frequency of behavioural problems in such infants, but cross-cultural comparisons are lacking. Our aim was to compare behavioural problems in ELBW children of similar ages from four countries. METHODS We prospectively studied 408 ELBW children aged 8-10 years, whose parents completed the child behaviour checklist. The children came from the Netherlands, Germany, Canada, and USA. The checklist provides a total problem score consisting of eight narrow-band scales. Of these, two (aggressive and delinquent behaviour) give a broad-band externalising score, three (anxious, somatic, and withdrawn behaviour) give a broad-band internalising score, and three (social, thought, and attention problems) indicate difficulties fitting neither broad-band dimension. For each cohort we analysed scores in ELBW children and those in normal- birthweight controls (two cohorts) or national normative controls (two cohorts). Across countries, we assessed deviations of the ELBW children from normative or control groups. FINDINGS ELBW children had higher total problem scores than normative or control children, but this increase was only significant in European countries. Narrow-band scores were raised only for the social, thought, and attention difficulty scales, which were 0.5-1.2 SD higher in ELBW children than in others. Except for the increase in internalising scores recorded for one cohort, ELBW children did not differ from normative or control children on internalising or externalising scales. INTERPRETATION Despite cultural differences, types of behavioural problems seen in ELBW children were very similar in the four countries. This finding suggests that biological mechanisms contribute to behavioural problems of ELBW children.

A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants

A multicenter prospective, randomized controlled trial was conducted to determine whether early use of platelet concentrates would reduce the incidence or extension of intracranial hemorrhage or both in sick preterm infants with thrombocytopenia. The effects on bleeding as reflected by the amount of blood product support administered and a shortened bleeding time were assessed as secondary outcomes. Premature infants with a platelet count < 150 x 10(9)/L within the first 72 hours of life were randomly assigned to receive either conventional therapy or conventional therapy plus platelet concentrates (10 ml/kg). The platelet count was maintained < 150 x 10(9)/L until day 7 of life by one to three platelet transfusions. In 22 (28%) of the 78 treated infants and 19 (26%) of the 74 control infants, either a new intracranial hemorrhage developed or an already-present one became more extensive (p = 0.73). Similar numbers of infants had each grade of intracranial hemorrhage on both initial and follow-up ultrasonography. Similar numbers of infants received fresh frozen plasma and packed red blood cells, but treated infants received less of both. The bleeding time was prolonged in the treated group before the infusion of platelet concentrates but subsequently shortened (mean difference, 79.0; 95% confidence interval, 73.1 to 84.9). Subanalysis of the control group showed that infants with platelet counts < 60 x 10(9)/L (n = 21) on at least one occasion received more fresh frozen plasma and packed red blood cells than did those with platelet counts > 60 x 10(9)/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical impact of neonatal thrombocytopenia

In a 1-year prospective study, the outcome in infants with a platelet count less than 100 X 10(9)/L (n = 97) was compared with the outcome in an age-, weight-, and disease-matched nonthrombocytopenic control group (n = 80). The hemostatic impact of the thrombocytopenia was assessed by modified template bleeding time, hemorrhage score, and determination of the presence and extent of intraventricular hemorrhage (IVH) in thrombocytopenic infants weighing less than 1500 at birth (n = 39) compared with all nonthrombocytopenic infants less than 1500 g (n = 122) admitted during the study period. The development outcome in infants less than 1500 g was compared at 12 months after delivery. Neonatal thrombocytopenia had a major impact on hemostatic integrity: bleeding time was inversely related to platelet count (r = -0.56, P less than 0.001) and became prolonged when the platelet count fell to less than 100 X 10(9)/L. In addition, many infants (40%) had evidence of platelet dysfunction with prolonged bleeding times despite only moderately reduced platelet counts (75 to 150 X 10(9)/L). The hemorrhage score was greater in the thrombocytopenic infants compared with the sick control infants, and increased as the platelet count fell (r = -0.58, P less than 0.001). The incidence of IVH in thrombocytopenic infants less than 1500 g was 78%, compared with 48% in the nonthrombocytopenic infants (P less than 0.01). In addition, the more severe grades of IVH were more frequent in the thrombocytopenic infants. The serious neurologic morbidity for the surviving infants less than 1500 g was 41% in the thrombocytopenic infants and 7% in the nonthrombocytopenic infants. Thus, on the basis of three indices of abnormal bleeding, thrombocytopenic infants are at greater risk for bleeding than equally sick nonthrombocytopenic infants. The thrombocytopenia itself may have contributed to the high mortality and neurologic morbidity.

Self-Perceived Health-Related Quality of Life of Former Extremely Low Birth Weight Infants at Young Adulthood

OBJECTIVES. The goals were to compare the self-reported, health-related quality of life of former extremely low birth weight and normal birth weight infants at young adulthood and to determine whether there were any changes over time. METHODS. A prospective, longitudinal, population-based study with concurrent control subjects was performed. We interviewed 143 of 166 extremely low birth weight survivors (birth weight: 501–1000 g; 1977–1982 births) and 130 of 145 sociodemographically comparable, normal birth weight, reference subjects. Neurosensory impairments were present for 27% extremely low birth weight and 2% normal birth weight young adults. Health Utilities Index 2 was used to assess health status, and standard gamble technique was used to measure directly the self-reported, health-related, quality of life and 4 hypothetical health states. RESULTS. Extremely low birth weight young adults reported more functional limitations in cognition, sensation, mobility, and self-care, compared with control subjects. There were no differences between groups in the mean self-reported, health-related, quality of life or between impaired (n = 38) and nonimpaired (n = 105) extremely low birth weight subjects. However, with a conservative approach of assigning a score of 0 for 10 severely disabled, extremely low birth weight subjects, the mean health-related quality of life was significantly lower than control values. Repeated-measures analysis of variance to compare health-related quality-of-life measurements obtained for young adults and teens showed the same decline in scores over time for both groups. There were no differences between groups in the ratings provided for the hypothetical health states. CONCLUSIONS. At young adulthood, health-related quality of life was not related to size at birth or to the presence of disability. There was a small decrease in health-related quality-of-life scores over time for both groups.

Comparison of current health, functional limitations, and health care use of young adults who were born with extremely low birth weight and normal birth weight.

OBJECTIVE. The objective of this study was to compare the current health status, physical ability, functional limitations, and health care use of extremely low birth weight and normal birth weight young adults. METHODS. A longitudinal study was conducted of a population-based cohort of 166 extremely low birth weight survivors (501–1000 g birth weight; 1977–1982 births) and a group of 145 sociodemographically comparable normal birth weight individuals. Current health status, history of illnesses, hospitalizations, use of health resources, and physical self-efficacy were assessed through questionnaires that were administered to the young adults by masked interviewers. RESULTS. Individuals completed the assessments at a mean age of 23 years. Neurosensory impairments were identified in 27% of extremely low birth weight and 2% of normal birth weight individuals. No differences were reported in the current health status for physical or mental summary scores. Extremely low birth weight young adults reported a higher prevalence of chronic health conditions in the past 6 months. A significantly higher proportion of extremely low birth weight individuals had functional limitations in seeing, hearing, and dexterity and experienced clumsiness and learning difficulties. Except for prescription glasses, medications for depression, and home-care services for extremely low birth weight individuals, there were no significant differences between groups in use of health care resources. Extremely low birth weight individuals had significantly weaker hand grip strength and lower scores for physical self-efficacy, perceived physical ability, and physical self-confidence. CONCLUSIONS. Extremely low birth weight young adults seem to enjoy similar current health status to their normal birth weight peers. However, they continue to have significantly poorer physical abilities and a higher prevalence of chronic health conditions and functional limitations. Contrary to expectations, they do not pose a significant burden to the health care system at young adulthood.

Intellectual and functional status at school entry of children who weighed 1000 grams or less at birth: A regional perspective of births in the 1980s

The intellectual and functional status of a regional cohort of children who weighed 501 to 1000 gm when born between 1980 and 1982 was evaluated at a mean age of 5 1/2 years by standard psychometric tests. Of 90 long-term survivors (survival rate 49%), 78 children (87%) had the full test battery, 5 children (6%) had other tests (4 were blind), and one child was untestable. Most of the mean scores were within 1 SD of the test norms; the lowest scores were in the McCarthy Motor scale and in the Beery Test of Visual-Motor Integration. Children without neurologic impairments and those with an IQ greater than or equal to 68 (n = 60) had higher overall scores but still performed poorly on the Motor subscale and the Beery test. Children who weighed less than 800 gm at birth (n = 28) were similar to those who weighed greater than 800 gm (n = 50), except in the Memory and Motor subscales, in which they performed significantly less well. At a functional level, determined by the Vineland Adaptive Behaviour Scales, two thirds of the children were performing in the adequate range and the remainder in the moderately low to low range. Of the 43 children with no neurosensory impairments and an IQ greater than or equal to 84, 49% were identified (by the Florida Kindergarten Screening Battery) to be at mild to high risk for future learning disabilities. The data from this unselected population provide an unbiased estimate of the prevalence of intellectual and functional problems in children who weighed less than or equal to 1000 gm at birth.

Decreased disability rate among 3-year-old survivors weighing 501 to 1000 grams at birth and born to residents of a geographically defined region from 1981 to 1984 compared with 1977 to 1980+

In this article we report the survival and morbidity rates for all live-born infants weighing 501 to 1000 gram at birth and born to residents of a defined geographic region from 1977 to 1980 (n = 255) compared with 1981 to 1984 (n = 266). During these periods, there were no changes in the proportion of infants delivered at the tertiary care center or community hospitals (171/84 vs 194/72); use of the tertiary care center increased only slightly, from 84% to 91%; and changes in neonatal management were mainly in improvements in diagnostic and monitoring techniques. When infants were grouped according to birth weights in 100 gm increments, survival improved significantly only for infants weighing between 501 and 600 gm at birth (2% vs 20% p less than 0.001). There were no differences in the overall survival rates to hospital discharge (46% vs 48%). The prevalence of neurosensory impairments was 24% in period 1 and 17% in period 2. There was a significant improvement in the proportion of infants considered to have disabilities by a functional classification assigned at 3 years corrected age (50% vs 27%, p less than 0.001), but only for infants weighing more than 800 gm at birth (49% vs 22%, p less than 0.001). Infants delivered at the community hospitals had a higher prevalence of neurosensory impairments compared with infants delivered at the tertiary care center (period 1, 35% vs 21%, not significant; period 2, 37% vs 14%, p less than 0.05). These data are encouraging; further efforts should be directed toward assessing which, if any, components of perinatal care are contributing to the improvement in morbidity rates.