Long-term child follow-up after large obstetric randomised controlled trials for the evaluation of perinatal interventions: a systematic review of the literature.

BACKGROUND: Although the hope is that many perinatal interventions are performed with an ultimate aim to improve the long-term health and development of the child, long-term outcome is rarely used as a primary end-point in perinatal randomised controlled trials (RCTs). OBJECTIVE: To evaluate how often and with which tools long-term follow-up is performed after large obstetric RCTs. SEARCH STRATEGY: We searched the Cochrane Library for Cochrane reviews published by the Cochrane Pregnancy and Childbirth Group for reviews on interventions that aimed to improve neonatal outcome. Selection criteria Reviews on perinatal interventions that were not performed to improve the condition of the neonate were excluded. We limited our review to RCTs with more than 350 participating women. For each included study, we checked in Web of Science as to whether the researchers had reported on follow-up in subsequent publications. DATA COLLECTION AND ANALYSIS: Relevant information was extracted from these RCTs by two reviewers using a predefined data collection sheet. All information was analysed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA). MAIN RESULTS: We studied 212 reviews including 1837 RCTs on perinatal interventions, 249 (14%) of which included 350 participants. Only 40 of 249 RCTs (16%) followed the children after discharge from the hospital to evaluate the effect of a specific perinatal intervention. The number of RCTs with long-term follow-up remained stable, with 10 of 67 RCTs (15%) reporting follow-up before 1990, 17 of 115 (15%) between 1990 and 2000, and 13 of 67 (19%) after 2000 (P = 0.68). CONCLUSIONS: Only a small minority of large perinatal RCTs report the long-term follow-up of the child. Future obstetric RCTs should consider performing long-term follow-up at the start of the trial.

Visual perception and visual-motor integration in very preterm and/or very low birth weight children: a meta-analysis.

A range of neurobehavioral impairments, including impaired visual perception and visual-motor integration, are found in very preterm born children, but reported findings show great variability. We aimed to aggregate the existing literature using meta-analysis, in order to provide robust estimates of the effect of very preterm birth on visual perceptive and visual-motor integration abilities. Very preterm born children showed deficits in visual-spatial abilities (medium to large effect sizes) but not in visual closure perception. Tests reporting broad visual perceptive indices showed inconclusive results. In addition, impaired visual-motor integration was found (medium effect size), particularly in boys compared to girls. The observed visual-spatial and visual-motor integration deficits may arise from affected occipital-parietal-frontal neural circuitries.

Parenting stress in mothers after very preterm birth and the effect of the Infant Behavioural Assessment and Intervention Program.

OBJECTIVE: Purpose of this study was to examine maternal parenting stress as a secondary outcome of the Infant Behavioural Assessment and Intervention Program (IBAIP). METHODS: In a randomized controlled trial 86 very preterm infants and their parents were assigned to the intervention group and 90 to the control group. Maternal parenting stress was assessed with the Dutch version of the Parenting Stress Index at 12 and 24 months post term. RESULTS: Mothers in the intervention group mothers assessed their infants as happier and less hyperactive/distractible compared with the control group mothers. However, mothers in the intervention group reported more feelings of social isolation. CONCLUSIONS: The IBAIP appears to have made mothers more satisfied about their infants' mood and distractibility, but also may have evoked more feelings of social isolation. Next to long-term evaluation of the development in very preterm born children, follow-up on functioning of their parents is important.

General movements in infants born from mothers with early-onset hypertensive disorders of pregnancy in relation to one year's neurodevelopmental outcome.

BACKGROUND: Assessment of general movements (GMs) at three months is considered useful for prediction of adverse neurological outcome in high risk infants. AIMS: To study the prevalence of abnormal GMs in infants born from women with early-onset hypertensive disorders of pregnancy and the association of GMs with neurodevelopmental outcome at one year. STUDY DESIGN: Prospective study, part of a randomised controlled trial of pre-birth management strategies. SUBJECTS: Infants born from women with early-onset hypertensive disorders of pregnancy. OUTCOME MEASURES: GMs observation and neurological examination at term and three months corrected age; at one year neurological examination and Bayley Scales of Infant Development. RESULTS: From 216 women included, 175 of 178 surviving infants (mean gestational age 31.6 weeks [SD 2.3], mean birth weight 1346 grams [SD 458]), were examined at three months. At term age normal, mildly abnormal and definitely abnormal GMs were observed in 54%, 36% and 10% respectively; and at three months in 47%, 40% and 13%. Mildly or definitely abnormal GMs at three months were not associated with abnormal neurological examination at one year, however, they were associated with delayed psychomotor development at one year (p = 0.01). CONCLUSIONS: In this prospective study, including small for gestational age, preterm infants about half of them did not have normal GMs at term and three months. There was no association of GMs at term nor three months with neurological outcome at one year, but there was a significant association of GMs at three months with one year psychomotor development.

Applying Dutch and US versions of the BSID-II in Dutch children born preterm leads to different outcomes.

The aim of the present study was to evaluate whether the application of Dutch versus US test procedures and norms of the Bayley Scales of Infant Development - 2nd edition (BSID-II) leads to different developmental outcomes. The BSID-II was administered to 376 preterm infants (191 males, 185 females; mean gestational age 30wks [SD 2.7], mean birth-weight 1242g [SD 385]) at corrected ages of 6, 12, 24, and/or 36 months. Raw scores were calculated twice with US and Dutch test procedures. Raw scores as well as Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) scores, calculated on the basis of Dutch versus US normative data, were compared. Small but statistically significant Dutch-US differences were found between raw scores. Large, clinically relevant Dutch-US differences were found for MDI and PDI scores, especially at 6 and 12 months. These differences were likely to have been caused by a bias in the Dutch normative data, although a slower developmental pace of Dutch children in general could also have a role. This study highlights the problems that can occur when using a test that was developed in another country, even when local standardization is available.

One-year infant outcome in women with early-onset hypertensive disorders of pregnancy.

OBJECTIVES: To evaluate the role of plasma volume expansion on 1-year infant outcome after severe hypertensive disorders of pregnancy and to determine prognostic factors for adverse neurodevelopmental infant outcome. DESIGN: Randomised controlled trial, observational prognostic study. SETTING: Two university hospitals in Amsterdam, The Netherlands. POPULATION: One hundred and seventy-two infants alive of 216 mothers with severe hypertensive disorders of pregnancy who were randomised for a temporising management strategy with or without plasma volume expansion. METHODS: At 1 year of corrected age, a neurological examination according to Bayley (mental development index [MDI] and psychomotor development index [PDI]) and Touwen was performed. MAIN OUTCOME MEASURES: Adverse neurodevelopmental infant outcome was defined as a MDI/PDI score below 70 and/or an abnormal Touwen. Risk factors for adverse neurodevelopmental outcome were explored by univariate and multivariate analyses. RESULTS: Adverse neurodevelopmental infant outcome was observed in 31 infants (18%). There were no differences between the randomisation groups. In multivariate analysis, an association with abnormal umbilical artery/middle cerebral artery Doppler ratio higher than the median, major neonatal morbidity, higher education of the parents, multiparity and Caucasian ethnicity was observed. CONCLUSION: Nearly 70% of the infants were alive at 1 year without adverse neurodevelopmental outcome. Maternal plasma volume expansion during pregnancy has no effect on 1-year infant outcome. The prediction of adverse outcome at 1 year by perinatal parameters is limited.

Long-term follow up of children exposed in utero to nifedipine or ritodrine for the management of preterm labour.

OBJECTIVE: To compare the long-term psychosocial and motor effects on children exposed in utero to nifedipine or ritodrine for the management of preterm labour. DESIGN: Randomised controlled trial. SETTING: Multicentre study in two university and one primary hospital in the Netherlands. POPULATION: In the original trial, 185 women were randomised to either nifedipine (n = 95) or ritodrine (n = 90). Of the 185 liveborn children, 171 survived (92%), and of these 102 (61%) were followed up at age 9-12 years. METHODS: Age-specific questionnaires were administered to the parent and teacher. Additional data were obtained from medical records. MAIN OUTCOME MEASURES: Questionnaires were used to assess the child's behavioural-emotional problems, quality of life (QoL), motor functioning, parenting distress and the child's education. RESULTS: Of the 171 eligible families, 102 (61%) agreed to participate and completed the questionnaires. Response was equal in the ritodrine group (n = 54 of 83 surviving children, 65%) compared with the nifedipine group (n= 48 of 88 surviving children, 55%). After controlling for differing perinatal characteristics at birth, no significant differences between the groups were detected with respect to long-term behaviour-emotional outcome, QoL, education, motor functioning or parenting distress. Psychosocial outcome was slightly better in the nifedipine group. CONCLUSIONS: The results do not support any differential postnatal effect of the tocolytic agents ritodrine or nifedipine on the child's long-term psychosocial and motor functioning. The slightly better outcome of children randomised in the nifedipine group is most likely due to more favourable perinatal outcomes in this group. These results merit further investigation in a larger group of survivors.

[Preimplantation genetic screening for numerical chromosomal abnormalities in embryos from women of 35 years of age and older; first results in The Netherlands]. / Preïmplantatiegenetische screening op numerieke chromosoomafwijkingen bij embryo's van vrouwen van 35 jaar en ouder; de eerste resultaten in Nederland.

OBJECTIVE: To assess the results of preimplantation genetic screening (PGS) for numerical chromosomal abnormalities in embryos from women of 35 years of age and older. DESIGN: Prospective, descriptive. METHOD: Women who were at least 35 years received standard IVF/ICSI treatment including ovarian hyperstimulation, after which matured oocytes were recovered and inseminated. Three days after insemination, one cell was biopsied from each of the available embryos. In these cells, the copy number of 5 (first 21 patients) or 8 chromosomes was determined using fluorescence in situ hybridisation (FISH). Only embryos with a normal or unknown FISH result were implanted in the uterus. Data were collected in an electronic database. RESULTS: PGS was done for 28 IVF- and 22 ICSI-treatments; the average age of the 50 women at the beginning of treatment was 38.5 years. There were 360 embryos generated; of the 288 biopsied embryos 156 (54%) contained an abnormal number of chromosomes. In 45 women, 1 or 2 embryos were transferred. This resulted in 8 ongoing pregnancies (8/50; 16%) and the birth of 9 children, all of whom were found to be healthy on a paediatric examination at 3 to 10 months of age. In 4 cases there was no embryo transfer because all the embryos were chromosomally abnormal. CONCLUSION: In the first 50 patients in The Netherlands, PGS resulted in an ongoing pregnancy rate of 16% per woman. All children showed normal growth and development.

Neonatal thyroxine supplementation in very preterm children: developmental outcome evaluated at early school age.

OBJECTIVE: Transient hypothyroxinemia in very premature infants is associated with developmental problems. A randomized, placebo-controlled trial of thyroxine (T(4)) supplementation was conducted in a group of 200 infants <30 weeks' gestation. T(4) supplementation improved mental outcome at 2 years old in children of 25/26 weeks' gestation only. The effect of T(4) supplementation beyond 2 years of age is unknown. We present the effects of neonatal T(4) supplementation on outcome at early school age. METHODS: Standardized measurements were used to assess cognitive, behavioral, and motor outcome, as well as a qualitative assessment of neurologic functioning. Survivors of the T(4) trial were assessed at the age of 5.7 years. RESULTS: Ninety-nine percent of the 157 survivors participated. Outcome on all domains was comparable between the T(4) group and placebo group. In children <27 weeks' gestation, a 10 IQ point difference was found in favor of the T(4) group, whereas in children of 29 weeks' gestation, a difference of 15 IQ points was found in favor of the placebo group. Teachers' reports showed less behavioral problems in the T(4)-treated children of 25/26 weeks' gestation, but more behavioral problems in the T(4)-treated children of 27 weeks' gestation. Differences in motor outcome and neurologic outcome were in favor of the T(4)-treated children <29 weeks' gestation, but not of the T(4)-treated children of 29 weeks' gestation. CONCLUSIONS: We found benefits of T(4) supplementation for children <29 weeks' gestation, and especially in children of 25/26 weeks' gestation. However, in children of 29 weeks' gestation T(4) supplementation is associated with more developmental problems.

Postnatal thyroid hormone replacement in very preterm infants.

Transient hypothyroxinemia occurs frequently in very preterm infants and is caused by a combination of factors as immaturity of the hypothalamo-pituitary-thyroid system, loss of the maternal thyroxine (T4) contribution, immaturity of thyroid hormone metabolism, and neonatal illness. Thyroid hormone is important in maturation of the brain, but also of heart and lungs. Low neonatal T4 concentrations in plasma are related to worse clinical and neurodevelopmental outcome. Despite these relationships, only few randomized clinical trials have been performed to find out whether T4 supplementation can improve clinical and/or neurodevelomental outcome of preterm infants. The currently available evidence does not support use of supplemental T4 in all preterm infants. There are, however, indications that T4 might improve neurodevelopmental outcome in infants born before 27 to 29 weeks of gestation. Therefore, it is necessary that new trials are set up to further study the benefits of thyroid hormones given in the neonatal period of very preterm infants.

Evaluation of the effect of thyroxine supplementation on behavioural outcome in very preterm infants.

Two-hundred infants of <30 weeks gestational age were included in a randomized double-blind controlled trial to study the effect of thyroxine administration on neurodevelopmental outcome in very preterm children. The infants were given either a fixed dose of thyroxine (8 microg/kg birthweight/day) or placebo for the first 6 weeks of life. This paper evaluates the effect of thyroxine administration on behavioural outcome at the age of 2 years. More externalizing, especially destructive, behaviours were found in the group given thyroxine than in the placebo group. This difference was more pronounced in boys and in children born after 27 weeks' gestation. The thyroxine-treated children with behavioural problems had lower plasma-free thyroxine levels than the thyroxine-treated children without behavioural problems. This finding suggests that the presence of more behavioural problems in the group given thyroxine was not an immediate consequence of the treatment.

Thyroid function in very preterm newborns: possible implications.

Thyroid hormones are essential for brain maturation. Very preterm infants, who are at risk of neurodevelopmental disabilities also have low thyroxine (T4) and free thyroxine (FT4) values in the first weeks after birth. This transient hypothyroxinemia may in part be causal to the neurodevelopmental problems. We have carried out a randomized, double-blind, placebo-controlled trial with T4 in 200 infants less than 30 weeks gestation. T4 (or placebo) was given in fixed dose of 8 microg/kg birth weight per day during the first 6 weeks after birth. It resulted in a significant increase of T4, FT4, and reverse triiodothyronine (rT3). Thyrotropin (TSH) secretion was suppressed, and, probably as a result of TSH suppression, triodothyronine (T3) levels were decreased in the T4 group. Mortality was 14% in the T4 group and 21% in the placebo group (NS). No effect was found on morbidity. Heart rate was significantly higher in T4-treated infants less than 28 weeks gestation, but not in T4-treated infants 28 weeks or more, who had the highest FT4 levels. In the study groups as a whole, no clear effect of T4 administration was found on neurodevelopmental outcome. However, there was a strong trend toward improvement of adverse outcome, defined as death or abnormal developmental outcome at 2 years of age. In addition, mental outcome in a subgroup of T4-treated infants less than 27 weeks' gestation was significantly better than in placebo infants of the same age group. In conclusion, this trial does not clearly have conclusive results. New trials of thyroid hormone treatment should be carried out in preterm infants, in order to investigate whether indeed T4 supplementation is required in preterm infants less than 27 or 28 weeks gestation. Addition of T3 to the treatment schedule needs to be considered.

Thyroxine administration to infants of less than 30 weeks gestational age decreases plasma tri-iodothyronine concentrations.

OBJECTIVE: To investigate the effect on thyroid hormone metabolism of the administration of thyroxine to very preterm infants. DESIGN AND METHODS: Two hundred infants of less than 30 weeks gestation were enrolled into a randomized, double-blind, placebo-controlled trial. Thyroxine (T4) (at a fixed daily dose of 8 microg/kg birthweight) or placebo was started 12-24h after birth and discontinued 6 weeks later. Plasma concentrations of T4, tri-iodothyronine (T3), reverse T3 (rT3), TSH, and thyroxine-binding globulin were measured weekly during trial medication and 2 weeks thereafter. RESULTS: The T4 and the placebo group each comprised 100 infants. Antenatal, perinatal, and postnatal clinical characteristics were comparable in both groups. T4 and rT3 were significantly increased in the T4 group. TSH concentrations were depressed in the T4 group and T3 was significantly decreased, probably as a result of TSH depression. The T4/T3 and T4/rT3 ratios differed significantly between the two study groups. CONCLUSIONS: Daily T4 administration during the first 6 weeks after birth to infants of less than 30 weeks gestation prevents hypothyroxinemia, but decreases plasma T3 concentrations. Our finding possibly implies that very preterm infants should receive supplements of both T4 and T3.

Somatosensory evoked potentials in very preterm infants in relation to L-thyroxine supplementation.

OBJECTIVE: To study the effect of L-thyroxine supplementation on neurologic maturation in very preterm infants with transient hypothyroxinemia. DESIGN: Randomized, double-blind, placebo-controlled, L-thyroxine supplementation trial. SETTING: Level III neonatal intensive care unit. SUBJECTS: A total of 200 infants <30 weeks' gestational age. INTERVENTION: Subjects were randomly assigned to receive L-thyroxine (8 microg/kg birth weight per day) or a placebo during the first 6 weeks of life. METHODS: Median nerve somatosensory evoked potentials were recorded, measuring cortical N1 peak latency at 2 weeks of age, at term, and at 6 months (corrected) age. RESULTS: Cortical N1 peak latency was not decreased significantly in the L-thyroxine group compared with the placebo group throughout the study period. CONCLUSION: L-Thyroxine supplementation during the first 6 weeks of life did not decrease cortical N1 peak latency in infants of <30 weeks' gestational age.

Motor nerve conduction velocity in very preterm infants in relation to L-thyroxine supplementation.

BACKGROUND: Transient hypothyroxinemia is common in preterm infants and has been associated with neurodevelopmental dysfunction and slow nerve conduction velocity. It is still unknown whether L-thyroxine supplementation is required. During an L-thyroxine supplementation trial, motor nerve conduction velocity was measured to answer the question whether L-thyroxine supplementation improves motor nerve conduction velocity. METHODS: Two hundred infants < 30 weeks' gestational age were enrolled in a randomized, double-blind, placebo-controlled L-thyroxine supplementation trial. L-Thyroxine (8 micrograms/kg birthweight per day) or a placebo was administered during the first 6 weeks of life. Motor nerve conduction velocity was measured in the ulnar and posterior tibial nerve shortly after birth, at 2 weeks, at 40 weeks, and at 66 weeks postmenstrual age. RESULTS: At 2 weeks, the ulnar motor nerve conduction velocity had improved in the L-thyroxine group compared with the placebo group, although the difference was not statistically significant (difference between means: 0.8 msec; 95% CI: -0.13 to 1.80; p = 0.06). Later on, no effect of L-thyroxine supplementation on motor nerve conduction velocity was found. CONCLUSION: This study shows that in infants < 30 weeks' gestational age L-thyroxine supplementation during the first 6 weeks of life does not clearly improve motor nerve conduction velocity.

Thyroid function in very preterm infants: influences of gestational age and disease.

It is not known how immaturity and disease influence postnatal thyroid function in infants <30 wk of gestational age. We performed serial measurements of plasma thyroxine (T4), free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), TSH, and T4-binding globulin (TBG) in 100 infants of <30 wk of gestation, during the first 8 postnatal weeks, to investigate the influences of disease and gestational age on the time course of thyroid hormones. One hundred infants were divided twice into two groups: 1) in a group of 25-28 and of 28-30 wk of gestation; and 2) in a sick and a healthy group, with similar gestational ages. The time course of T4, FT4, T3, TSH, and TBG, but not rT3 differed significantly (p < 0.005) between the gestational age groups. T4 and FT4 decreased to levels below the cord blood value with a deeper FT4 nadir on d 7 in the youngest group. Disease decreased T4, FT4, T3, TSH, and TBG concentrations especially during the 1st wk after birth (p < 0.005). However, the FT4 nadir on d 7 was similar in sick and healthy infants. After 3 wk, T4, FT4, T3, and TBG were higher in the sick group compared with the healthy group. rT3 levels were not increased in sick infants. We conclude that the extent of the FT4 decrease after birth in infants of <30 wk gestation is mainly influenced by gestational age and probably reflects a transient depletion of thyroidal hormone reserves. rT3 cannot be used as a marker of nonthyroidal illness in very preterm infants.

Effects of thyroxine supplementation on neurologic development in infants born at less than 30 weeks' gestation.

BACKGROUND: Premature infants who have transient hypothyroxinemia in the first weeks of life may have developmental delay and neurologic dysfunction. Whether thyroxine treatment during this period results in improved developmental outcomes is not known. METHODS: We carried out a randomized, placebo-controlled, double-blind trial of thyroxine supplementation in 200 infants born at less than 30 weeks' gestation. Thyroxine (8 microg per kilogram of birth weight) or placebo was administered daily, starting 12 to 24 hours after birth, for six weeks. Plasma free thyroxine concentrations were measured weekly for the first eight weeks after birth. Scores on the Bayley Mental and Psychomotor Development Indexes and neurologic function were assessed at 6, 12, and 24 months of age (corrected for prematurity). RESULTS: Mortality and morbidity up to the time of discharge from the hospital were similar in the study groups. At 24 months of age, 157 infants were evaluated. Overall, neither mental nor psychomotor scores differed significantly between the study groups at any time, nor was the frequency of abnormal neurologic outcome significantly different. In thyroxine-treated infants born at gestational ages of less than 27 weeks, the score on the Bayley Mental Development Index at 24 months of age was 18 points higher than the score for the infants with similar gestational ages at birth in the placebo group (P=0.01); for thyroxine-treated infants born at 27 weeks or later, the mental-development score was 10 points lower than that of their counterparts in the placebo group (P=0.03). There was no relation between the initial plasma free thyroxine concentration and the effect of treatment. CONCLUSIONS: In infants born before 30 weeks' gestation, thyroxine supplementation does not improve the developmental outcome at 24 months.

Thyroid function in preterm newborns; is T4 treatment required in infants < 27 weeks' gestational age?

Thyroid hormones are essential for brain maturation. Very preterm infants, who are at risk of neurodevelopmental disabilities also have low T4 and FT4 values in the first weeks after birth. This transient hypothyroxinemia may in part be causal to the neurodevelopmental problems. We have carried out a randomised, double-blind, placebo-controlled trial with T4 in 200 infants < 30 weeks' gestation. In the study groups as a whole (n = 100 in the T4 group, n = 100 in the Placebo group), no clear effect of T4 administration was found. In this study we examined whether gestational age influenced the effect of T4 administration. The T4- and placebo groups were subdivided into 4 groups according to gestational age. FT4-values during the first weeks after birth were lowest in the youngest gestational age group in the T4 as well as in the placebo group. In this group with infants < 27 weeks' gestation mental developmental outcome at 2 years of age was significantly better than in the placebo group of the same gestational age. There was also a trend towards a better psychomotor and neurological outcome. Beyond 27 weeks' gestation, no clear effect of T4 could be found; on the contrary, a possible harmful effect on mental developmental outcome might be the result. In conclusion. T4 treatment possibly improves developmental outcome in infants < 27 weeks' gestation, but seems not necessary beyond this gestational age.

Thyroxine administration to infants of less than 30 weeks' gestational age does not increase plasma triiodothyronine concentrations.

Very preterm infants (less than 30 weeks' gestational age) were treated with thyroxine in three different dosage schemes: 10, 8 and 6 micrograms.kg-1 birthweight.day-1 during the first 6 weeks of life. The aim was to prevent transient hypothyroxinemia of the preterm infant. Plasma levels of thyroxine, free thyroxine, triiodothyronine, reverse triiodothyronine, thyroxine-binding globulin and thyrotropin were measured weekly. Thyroxine administration increased thyroxine and free thyroxine levels most properly in the 8-micrograms supplementation group. It did not result in a change in plasma triiodothyronine levels. Levels of reverse triiodothyronine increased in relation to the thyroxine dosage. Thyrotropin secretion was suppressed in the 6- and 8-micrograms groups during the first 2 weeks, while in the 10-micrograms group suppression lasted 4 weeks. No clinical adverse effects of thyroxine administration were seen. We conclude that 8 micrograms thyroxine.kg-1 birthweight.day-1 for 6 weeks prevents transient hypothyroxinemia. The finding that plasma triiodothyronine concentrations are not influenced by thyroxine administration suggests a specific maturation process in the deiodination of thyroxine.

New insights into lactase and glycosylceramidase activities of rat lactase-phlorizin hydrolase.

Lactase-phlorizin hydrolase, a small intestinal disaccharidase, has been considered mainly an enzyme important only for the hydrolysis of lactose. After weaning in most mammals lactase-specific activity falls markedly, and, functionally, adult mammals are considered to be lactase deficient. However, the persistence of low levels of lactase activity in adulthood has never been explained. In addition, it has been suggested that lactase-phlorizin hydrolase is associated with glycosylceramidase activity when the enzyme is prepared by column chromatography, but it is unclear whether this represents copurified activities or two catalytic sites on one peptide. The developmental patterns of lactase-phlorizin hydrolase and other disaccharidases were investigated in homogenates of total rat small intestine; lactase and several glycosylceramidases were measured in immunoprecipitates from these homogenates using a monoclonal antibody. The developmental pattern of total lactase activity showed a steady 2.3-fold increase to adult levels (specific activity decreased eightfold), whereas total phlorizin-hydrolase activity increased 10.7-fold (specific activity decreased threefold). As expected, levels of both total and specific sucrase and maltase activities increased during development. In lactating rats total lactase activity showed a significant increase compared with adult males. The developmental pattern of the enzyme activities for the glycolipid substrates was similar to that found for lactase, and the immunoprecipitated enzyme showed a 40- to 55-fold higher affinity for the glycolipids than for lactose. Galactosyl- and lactosylceramide inhibited lactose hydrolysis by 38%, without a competitive pattern, suggesting two different active sites for lactose and glycolipid hydrolysis, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)