Maternal physical activity affects yolk sac size and growth in early pregnancy, but girls and boys use different strategies.

This longitudinal study investigated the impact of actigraphy-measured maternal physical activity on yolk sac size during early development. The yolk sac, a transient extraembryonic organ, plays a crucial role in embryonic development and is involved in metabolism, nutrition, growth, and hematopoiesis. Prospectively collected data from 190 healthy women indicated that their total daily physical activity, including both light and moderate-vigorous activity, was associated with yolk sac growth dynamics depending on embryonic sex and gestational age. Higher preconception maternal physical activity was linked to a larger yolk sac at 7 weeks (95% CI [0.02-0.13 mm]) and a smaller yolk sac at 10 weeks' gestation (95% CI [- 0.18 to - 0.00]) in male embryos; in female embryos, the yolk sac size was increased at 10 weeks' gestation (95% CI [0.06-0.26]) and was, on average, 24% larger than that in male embryos (95% CI [0.12-0.38]). Considering the pattern of other maternal effects on yolk sac size-e.g., body composition and sleep duration-we suggest that physiological yolk sac adaptations occur in short, sex-specific time windows and can be influenced by various maternal factors.

Time trends in perinatal outcomes among HIV-positive pregnant women in Northern Tanzania: A registry-based study.

INTRODUCTION: Maternal HIV infection is associated with increased risk of having a preterm delivery, low birth weight baby, small for gestational age baby and stillbirth. Maternal use of combination antiretroviral treatment is also associated with preterm delivery and low birth weight, although the effects vary by the type of drugs and timing of initiation. OBJECTIVE: To examine time trends in adverse perinatal outcomes among HIV-positive compared with HIV-negative women. DESIGN: Registry-based cohort study. SETTING: Northern Tanzania, 2000-2018. STUDY SAMPLE: Mother-baby pairs of singleton deliveries (n = 41 156). METHODS: Perinatal outcomes of HIV-positive women were compared with HIV-negative women during time periods representing shifts in prevention of mother-to-child transmission guidelines. Monotherapy was used as first-line therapy before 2007 while combination antiretroviral treatment was routinely used from 2007. Log binomial and quantile regression were used to analyze the data. MAIN OUTCOME MEASURES: Preterm delivery, low birth weight, perinatal death, stillbirth, low Apgar score, transfer to neonatal care unit and small for gestational age. RESULTS: Overall, maternal HIV infection was associated with a higher risk of low birth weight and small for gestational age. Moreover, this pattern became more pronounced over time for low birth weight, the last time period being an exception. For other outcomes we found none or only a small overall association with maternal HIV infection, although a trend towards higher risk over time in HIV-positive compared with HIV-negative women was observed for preterm delivery and perinatal death. Quantile regression showed an increase in birth weight in babies born to HIV-negative women over time and a corresponding decline in birth weight in babies born to HIV-positive women. CONCLUSION: Unfavourable trends in some of the selected perinatal outcomes were seen for HIV-positive compared with HIV-negative women. Potential side-effects of combination antiretroviral treatment in pregnancy should be further explored.

Maternal antiretroviral treatment for HIV infection and risk of small-for-gestational-age birth: A systematic review and meta-analysis of protease inhibitor-based treatment and timing of treatment.

BACKGROUND: Data indicate that certain combination antiretroviral treatment (cART) regimens, particularly protease inhibitor (PI)-based regimens, and cART initiation before conception may be associated with adverse pregnancy outcomes. The risk of having a small-for-gestational-age (SGA) infant was examined among pregnant HIV-infected mothers on 1) PI-based compared to non-PI-based cART, and 2) any cART initiated before compared to after conception. METHODS: A search was conducted using PubMed, Embase, and the Cochrane Library, and a systematic review was performed of studies published since Dec 1, 1995. Effect estimates with 95% confidence intervals (CIs) were extracted and meta-analyses with random-effects models were conducted. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. FINDINGS: Of 783 identified studies, 28 fulfilled the inclusion criteria. Meta-analysis indicated that PI-based cART was associated with a possible slightly increased risk of SGA compared with non-PI-based cART (pooled odds ratio [OR]: 1·09; CI: 0·76, 1·55). Initiation of cART before conception was also associated with a possible slightly increased risk of SGA compared with after conception (pooled OR: 1·08; CI: 0·95, 1·22). The overall certainty of evidence was very low and low for the first and second research questions, respectively. INTERPRETATION: Although the benefits of cART largely outweigh the risks, these findings indicate the possibility of slightly increased risks of having an SGA infant. This indicates that careful monitoring of fetuses exposed to PI-based cART or cART before pregnancy might be reasonable. Based on the uncertainty of evidence, further research may change this conclusion.

Effect of maternal sleep on embryonic development.

The concept of developmental origin of health and disease has ignited a search for mechanisms and health factors influencing normal intrauterine development. Sleep is a basic health factor with substantial individual variation, but its implication for early prenatal development remains unclear. During the embryonic period, the yolk sac is involved in embryonic nutrition, growth, hematopoiesis, and likely in fetal programming. Maternal body measures seem to influence its size in human female embryos. In this prospective, longitudinal observational study of 190 healthy women recruited before natural conception, we assessed the effect of prepregnant sleep duration (actigraphy) on the fetal crown-rump-length (CRL) and yolk sac size (ultrasound). All women gave birth to a live child. The prepregnancy daily sleep duration had an effect on the male yolk sac and CRL at the earliest measurement only (7 weeks). I.e., the yolk sac diameter decreased with increasing sleep duration (0.22 mm·h-1d-1, 95%CI [0.35-0.09], P < 0.01), and CRL increased (0.92 mm·h-1d-1, 95%CI [1.77-0.08], P = 0.03). Since there was no association at the second measurement (10 weeks), and in the group of female fetuses at any measure point, we suggest a sex- and time-dependent embryonic adaptation to sleep generated differences in the intrauterine environment in normal pregnancies.

Isolated oral clefts and school grades: population-based cohort study from Norway.

OBJECTIVE: To compare school grades of adolescents in Norway born with isolated cleft with those of their unaffected peers. DESIGN: Population-based cohort study. SETTING: Norway. PATIENTS: A total of 347 419 individuals born in Norway between 1986 and 1992, including 523 isolated cleft cases which were identified using data from Norway's two treatment centres. Individuals were followed from birth through compulsory school. MAIN OUTCOME MEASURES: Grade point average (GPA) from middle school graduation (around the age of 16). Specific subject grades were also investigated. RESULTS: Using a grade scale from 1-6, the observed mean GPA for the reference group was 3.99. Both cleft lip only (CLO) and cleft lip with cleft palate (CLP) had a mean GPA similar to the reference group (adjusted GPA differences from the reference with 95% CIs of 0.06 (-0.04 to 0.16) and -0.08 (-0.19 to 0.03), respectively). Cleft palate only (CPO) had a marginally lower GPA (adjusted GPA difference: -0.18 (-0.28 to -0.08)). These comparisons were consistent across specific subjects. Overall, the evidence suggests a larger difference in GPA between cases and controls in males compared with females. Females with CLO even had a higher estimated GPA than females in the reference group (adjusted GPA difference: 0.19 (0.013 to 0.36)). Grades were similar regardless of laterality of cleft lip (CLO or CLP). CONCLUSION: In Norway, individuals born with isolated CLO or CLP did not have lower average school grades when graduating from middle school. Individuals born with isolated CPO had marginally lower grades.

Sleep and physical activity from before conception to the end of pregnancy in healthy women: a longitudinal actigraphy study.

BACKGROUND: Sleep and physical activity changes are common in pregnancy, but longitudinal data starting before conception are scarce. Our aim was to determine the changes of the daily total sleep time (TST) and physical activity duration (PAD) from before conception to end of pregnancies in respect of pregestational maternal factors. METHODS: This longitudinal observational study formed part of the CONIMPREG research project and recruited healthy women planning to become pregnant. Sleep and physical activity were recorded around-the-clock for ≥4 days via actigraphy before conception and during each trimester of pregnancy. Data were adjusted according to pregestational maternal body composition, parity and age. RESULTS: Among 123 women with eligible data, the unadjusted mean (95% confidence interval) TST increased from 415.3 min (405.5-425.2 min) before conception to 458.0 min (445.4-470.6 min) in the 1st trimester, remaining high through the 2nd and 3rd trimesters. Variation was substantial before conception (±2SD range: 307-523 min). The unadjusted mean PAD before conception was 363.7 min (±2SD range: 120-608 min), decreasing sharply to 262.1 min in the first trimester and more gradually thereafter. Vigorous and moderate activity decreased more than light activity. TST and PAD were significantly associated with age, parity, and pregestational body fat percentage; lean body mass was negatively correlated with TST. Results were generally unaffected by seasonal variations. CONCLUSION: Marked variations were found in pregestational TST and PAD. Healthy women slept ≥30 min longer during pregnancy, while PAD decreased by ≥ 90 min in early pregnancy and continued to decrease thereafter.

Maternal Chronic Conditions and Risk of Cerebral Palsy in Offspring: A National Cohort Study.

BACKGROUND AND OBJECTIVES: Previous studies suggest that children of mothers with certain chronic conditions may be at increased risk of cerebral palsy (CP). We explored possible associations between 17 maternal chronic conditions and CP in offspring. METHODS: We conducted a prospective cohort study of Norwegian children born in 1990-2012 and surviving to 2 years of age. Information on maternal chronic conditions during pregnancy were extracted from the Medical Birth Registry of Norway (1990-2012). Information on chronic conditions in mothers and fathers recorded in the Norwegian Patient Registry (2008-2014) was available for a subset of children. CP diagnoses were extracted from the National Insurance Scheme (1990-2014) and the Norwegian Patient Registry (2008-2014). We estimated relative risks (RRs) and 95% confidence intervals (CIs) of CP in offspring of parents with chronic conditions compared with the general population using log binominal regression models. RESULTS: A total of 1 360 149 Norwegian children, including 3575 children with CP (2.6 per 1000 live births), fulfilled the inclusion criteria. The highest risk of CP was among offspring of mothers with type 2 diabetes (RR 3.2; 95% CI 1.8-5.4), lupus erythematosus (RR 2.7; 95% CI 0.9-8.3), type 1 diabetes (RR 2.2; 95% CI 1.4-3.4), and Crohn disease (RR 2.1; 95% CI 1.0-4.1) during pregnancy. No increased risks were seen for offspring of fathers with chronic conditions. CONCLUSIONS: Several maternal chronic conditions were associated with increased risk of CP in offspring. Maternal autoimmune disorders carried a particular risk.

Parental education and the risk of cerebral palsy for children: an evaluation of causality.

AIM: To explore whether increasing parental education has a causal effect on risk of cerebral palsy (CP) in the child, or whether unobserved confounding is a more likely explanation. METHOD: We used data from Norwegian registries on approximately 1.5 million children born between 1967 and 2011. We compared results from a traditional cohort design with results from a family-based matched case-control design, in which children with CP were matched to their first cousins without CP. In addition, we performed a simulation study to assess the role of unobserved confounding. RESULTS: In the cohort design, the odds of CP were reduced in children of mothers and fathers with higher education (adjusted odds ratio [OR] 0.67, 95% confidence interval [CI] 0.60-0.75 for maternal education, and adjusted OR 0.75, 95% CI 0.67-0.85 for paternal education). In the family-based case-control design, only an association for maternal education remained (adjusted OR 0.80, 95% CI 0.64-0.99). Results from a simulation study suggested that this association could be explained by unobserved confounding. INTERPRETATION: A causal effect of obtaining higher education on risk of CP in the child is unlikely. Results stress the importance of continued research on the role of genetic and environmental risk factors that vary by parents' educational level. WHAT THIS PAPER ADDS: Children of higher-educated parents had significantly lower odds of cerebral palsy (CP). There was no evidence of difference in risk of CP within first cousins whose mothers or fathers had different educational levels. Association between parental education and odds of CP did not reflect a causal effect.

Maternal complications in pregnancy and childbirth for women with epilepsy: Time trends in a nationwide cohort.

OBJECTIVE: Obstetric trends show changes in complication rates and maternal characteristics such as caesarean section, induced labour, and maternal age. To what degree such general time trends and changing patterns of antiepileptic drug use influence pregnancies of women with epilepsy (WWE) is unknown. Our aim was to describe changes in maternal characteristics and obstetric complications in WWE over time, and to assess changes in complication risks in WWE relative to women without epilepsy. METHODS: This was a nationwide cohort study of all first births in the Medical Birth Registry of Norway, 1999-2016. We estimated maternal characteristics, complication rates, and risks for WWE compared to women without epilepsy. Main maternal outcome measures were hypertensive disorders, bleeding in pregnancy, induction of labour, caesarean section, postpartum hemorrhage, preterm birth, small for gestational age, and epidural analgesia. Time trends were analyzed by logistic regression and comparisons made with interaction analyses. RESULTS: 426 347 first births were analyzed, and 3077 (0.7%) women had epilepsy. In WWE there was an increase in proportions of induced labour (p<0.005) and use of epidural analgesia (p<0.005), and a reduction in mild preeclampsia (p = 0.006). However, the risk of these outcomes did not change over time. Only the risk of severe preeclampsia increased significantly over time relative to women without epilepsy (p = 0.006). In WWE, folic acid supplementation increased significantly over time (p<0.005), and there was a decrease in smoking during pregnancy (p<0.005), but these changes were less pronounced than for women without epilepsy (p<0.005). CONCLUSIONS: During 1999-2016 there were important changes in maternal characteristics and complication rates among WWE. However, outcome risks for WWE relative to women without epilepsy did not change despite changes in antiepileptic drug use patterns. The relative risk of severe preeclampsia increased in women with epilepsy.

How should recruitment to public health surveys be conducted? / Hvordan bør rekrutteringen til folkehelseundersøkelsene gjennomføres?

BACKGROUND: The aim of the public health survey in the Norwegian counties is to obtain information that is useful for public health work. In 2018, two parallel data collection processes were undertaken in Hordaland county. Both samples were drawn randomly from the National Population Register, but one of these was limited to users of the helsenorge.no website. The purpose of this article is to investigate the degree to which limiting users to the helsenorge.no website leads to selection bias beyond the selection that occurs through ordinary non-participation. MATERIAL AND METHOD: Services for Sensitive Data (TSD) was used in the data collection for the sample drawn from the National Population Register (n = 36 000), and the helsenorge.no platform was used in the data collection for the sample limited to users of helsenorge.no (n = 30 000). The response rate was 40.8 % and 41.5 %, respectively. RESULTS: For some outcome measures, the differences between the two datasets were modest (gender distribution, age, education and health habits). For variables that were more directly related to health, the differences were greater. In the helsenorge.no sample a higher proportion reported generally poorer health (29.4 vs. 24.0 %), mental health problems (13.6 vs. 11.6 %), disability pension (10.5 vs. 7.8 %) and long-term illness (13.3 vs. 9.3 %). Analyses of subgroups showed more pronounced differences in the proportion with generally poorer health and mental health problems between those with low education in the helsenorge.no sample and the corresponding group in the sample from the National Population Register. INTERPRETATION: Systematic and pronounced differences between the samples show that limiting recruitment to users of helsenorge.no's services results in further selection problems.

Genome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth.

Infant and childhood growth are dynamic processes with large changes in BMI during development. By performing genome-wide association studies of BMI at 12 time points from birth to eight years (9286 children, 74,105 measurements) in the Norwegian Mother, Father, and Child Cohort Study, replicated in 5235 children, we identify a transient effect in the leptin receptor (LEPR) locus: no effect at birth, increasing effect in infancy, peaking at 6-12 months (rs2767486, P6m = 2.0 × 10-21, ß6m = 0.16 sd-BMI), and little effect after age five. We identify a similar transient effect near the leptin gene (LEP), peaking at 1.5 years (rs10487505, P1.5y = 1.3 × 10-8, ß1.5y = 0.079 sd-BMI). Both signals are protein quantitative trait loci for soluble-LEPR and LEP in plasma in adults independent from adult traits mapped to the respective genes, suggesting key roles of common variation in the leptin signaling pathway for healthy infant growth.

A genome-wide scan of cleft lip triads identifies parent-of-origin interaction effects between ANK3 and maternal smoking, and between ARHGEF10 and alcohol consumption.

Background: Although both genetic and environmental factors have been reported to influence the risk of isolated cleft lip with or without cleft palate (CL/P), the exact mechanisms behind CL/P are still largely unaccounted for. We recently developed new methods to identify parent-of-origin (PoO) interactions with environmental exposures (PoOxE) and applied them to families with children born with isolated cleft palate only. Here, we used the same genome-wide association study (GWAS) dataset and methodology to screen for PoOxE effects in the larger sample of CL/P triads. Methods: Genotypes from 1594 complete triads and 314 dyads (1908 nuclear families in total) with CL/P were available for the current analyses. Of these families, 1024 were Asian, 825 were European and 59 had other ancestries. After quality control, 341,191 SNPs remained from the original 569,244. The exposures were maternal cigarette smoking, use of alcohol, and use of vitamin supplements in the periconceptional period. The methodology applied in the analyses is implemented in the R-package Haplin. Results: Among Europeans, there was evidence of a PoOxSmoke effect for ANK3 with three SNPs (rs3793861, q=0.20, p=2.6e-6; rs7087489, q=0.20, p=3.1e-6; rs4310561, q=0.67, p=4.0e-5) and a PoOxAlcohol effect for ARHGEF10 with two SNPs (rs2294035, q=0.32, p=2.9e-6; rs4876274, q=0.76, p=1.3e-5). Conclusion: Our results indicate that the detected PoOxE effects have a plausible biological basis, and thus warrant replication in other independent cleft samples. Our demonstration of the feasibility of identifying complex interactions between relevant environmental exposures and PoO effects offers new avenues for future research aimed at unravelling  the complex etiology of cleft lip defects.

Correction: Time trends in management of HIV-positive pregnant women in Northern Tanzania: A registry-based study.

[This corrects the article DOI: 10.1371/journal.pone.0184362.].

Parental socioeconomic status and risk of cerebral palsy in the child: evidence from two Nordic population-based cohorts.

Background: We investigated whether the risk of cerebral palsy (CP) in the child varies by parents' socioeconomic status, in Denmark and Norway. Methods: We included almost 1.3 million children born in Demark during 1981-2007 and 2.4 million children born in Norway during 1967-2007, registered in the Medical Birth registries. Data on births were linked to Statistics Denmark and Norway to retrieve information on parents' education and relationship status and, in Denmark, also income. CP diagnoses were obtained from linkage with national registries. We used multivariate log-binominal regression models to estimate relative risk (RR) of CP according to parental socioeconomic status. Results: There was a strong trend of decreasing risk of CP with additional education of both the mother and the father. These trends were nearly identical for the two parents, with a one-third reduction in risk for those with the highest education compared with parents with the lowest education. When both parents had high education, risk of CP was further reduced (RR 0.58, 0.53-0.63). Women with partners had a reduction in risk (RR 0.79, 0.74-0.85) compared with single mothers overall. Risk patterns were stable over time, across countries and within spastic bilateral and unilateral CP. Household income was not associated with risk of CP. Conclusions: Risk of CP in two Scandinavian countries was lower among educated parents and mothers with a partner, but unrelated to income. Factors underlying this stable association with education are unknown, but could include differences in potentially modifiable lifestyle factors and health behaviours.

The association between pre pregnancy body mass index and risk of preeclampsia: a registry based study from Tanzania.

BACKGROUND: Preeclampsia is among the leading causes of maternal mortality and morbidity worldwide, occurs in 2-8% of all pregnancies, and is estimated to account for at least 9 % of maternal deaths in Africa. Studies from developed countries show that high pre pregnancy body mass index (BMI) increases the risk of preeclampsia. We examined the association between pre pregnancy BMI and the risk of preeclampsia in Tanzania, a low income country. METHODS: Data from the Kilimanjaro Christian Medical Center (KCMC) Medical Birth Registry recorded between July 2000 and May 2013 were used. We restricted the study population to singleton deliveries among women with no or one previous pregnancy. Pre pregnancy BMI (kg/m2) was categorized according to the WHO categories of underweight (less than 18.5), normal (18.5 - 24.9), overweight (25.0 - 29.9) and obese (30 or more). Potential confounders were adjusted for in multivariable analyses. RESULTS: Among the 17,738 singleton births, 6.6% of the mothers were underweight, 62.1% were of normal BMI, 24.0% were overweight, and 7.3% were obese. Five hundred and eighty-two pregnancies (3.3%) were affected by preeclampsia. Compared to those with normal BMI, overweight and obese women had a higher risk of preeclampsia (aOR (95% CI) 1.4 (1.2 - 1.8) and 1.8 (1.3 - 2.4)), respectively, while underweight women had a lower risk (0.7 (0.4-1.1)). CONCLUSIONS: Pre pregnancy maternal overweight and obesity were associated with an increased risk of preeclampsia in Tanzania. Risks were similar to those reported in high income countries.

Time trends in management of HIV-positive pregnant women in Northern Tanzania: A registry-based study.

OBJECTIVE: To examine time trends in antenatal factors and delivery characteristics in Northern Tanzania, and relate these to national guidelines for HIV in pregnancy. DESIGN: Registry-based study. SETTING: Northern Tanzania, 2000-2014. POPULATION OR SAMPLE: Deliveries (n = 33 346). METHODS: HIV-positive women were compared with HIV-negative women during four periods spanning changing national guidelines. MAIN OUTCOME MEASURES: Known maternal HIV status, HIV treatment for woman, number of antenatal care (ANC) visits, routine folate/iron in pregnancy, anemia, delivery complications/interventions. RESULTS: We observed an increase in deliveries with known maternal HIV status and women receiving HIV treatment, and a decline in deliveries with positive maternal HIV status (p-values for trend <0.001). The proportion of women with less than four ANC visits increased to above 30 percent irrespective of HIV status. Use of routine folate/iron increased, corresponding to a decrease in anemia which was strongest in HIV-negative women. Incidence of elective caesarean section (CS) and emergency CS remained unchanged for HIV-positive women (7.1% and 25.5%, respectively, in the last period). Use of invasive procedures declined in both groups of women. Mothers who were young, single, had low education, high parity or lived in the rural area more often had indicators of poor antenatal care. CONCLUSIONS: Increasing adherence to national guidelines over time was found for most selected outcomes. Still, a high occurrence of insufficient ANC, anemia and emergency CS call for efforts to explore and identify barriers that hinder optimal care.

Prenatal exposure to Chernobyl fallout in Norway: neurological and developmental outcomes in a 25-year follow-up.

Ionizing radiation at high doses early in life may cause neurodevelopmental problems. Possible effects of lower doses are, however, controversial. We use carefully collected exposure data for Norway following the Chernobyl accident in April 1986 combined with population-based registries to assess long-term effects of fetal exposure on neurodevelopmental outcomes. Radiation doses were estimated for each Norwegian municipality for each calendar month from May 1986 to April 1989. We established a cohort of all Norwegian pregnancies during the three-year period of radiation measurement and compared them with appropriate unexposed groups. All cohorts were followed into adulthood. Risks of cerebral palsy, mental retardation, schizophrenia, epilepsy, vision or hearing problems, school dropout, and low income were estimated. We also conducted an analysis of mathematics and language grades using siblings born after the exposure period as comparison. There was little evidence of associations between radiation exposure and cerebral palsy, mental retardation, schizophrenia, epilepsy, or hearing or vision problems associated with radiation exposure. (p-values for trend with exposure dose were 0.27, 0.14, 0.83, 0.35 and 0.42.) Slightly more of the exposed failed to complete high school (p = 0.05), but there was no increase in the proportion with low income (p = 0.38). The natural advantage of older siblings over younger siblings in mathematics grades was diminished with exposure of older siblings (p = 0.003), but there was no association of exposure with Norwegian language grades (p = 0.37). There is scant evidence that the low-dose fallout from Chernobyl in Norway increased the risk for serious neurodevelopmental problems. We cannot exclude the possibility of lower mathematics grades with exposure, similar to a report from Sweden.

Socio-Economic Status and Reproduction among Adults Born with an Oral Cleft: A Population-Based Cohort Study in Norway.

BACKGROUND: It has been reported that people born with orofacial clefts do worse in life than their peers regarding a range of social markers, such as academic achievement and reproduction. We have compared otherwise healthy individuals with and without clefts, to investigate if these differences are due to the cleft or other background factors. MATERIALS AND METHODS: In a retrospective national cohort study, based on compulsory registers with data collected prospectively, we included everybody born in Norway between 1967 and 1992 (1490279 individuals, 2584 with clefts). This cohort was followed until the year 2010, when the youngest individuals were 18 years old. In order to ensure that the individuals were not affected by unknown syndromes or diseases, we excluded all individuals with any chronic medical condition, or who had other birth defects than clefts, hydroceles and dislocated hips. Individuals with oral clefts who were included in the study are said to have isolated clefts. RESULTS: Isolated cleft patients are similar to the general population regarding education, income and social class. Isolated cleft patients have lower fertility than the background population, but considering only married couples this difference in fertility disappeared. CONCLUSIONS: An oral cleft did not appear to affect future socioeconomic status or chances of becoming a parent for children born in Norway. An exception was males with cleft lip and palate, but differences were small.