Early or late menarche is associated with reduced fecundability in the Norwegian Mother, Father and Child Cohort Study.

STUDY QUESTION: Is age at menarche associated with fecundability? SUMMARY ANSWER: Both early (<11 years) and late (>15 years) menarche is associated with decreased fecundability. WHAT IS KNOWN ALREADY: Previous studies on age at menarche and fecundability have been inconclusive. Women with early or late menarche are at increased risks of gynaecological and autoimmune diseases that may affect their ability to conceive. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study including 67 613 pregnant women, participating in the Norwegian Mother, Father and Child Cohort Study between 1999 and 2008, with self-reported information on age at menarche and time to pregnancy. We included planned pregnancies that were conceived either naturally or with the help of assisted reproductive technologies. PARTICIPANTS/MATERIALS, SETTING, METHODS: We calculated fecundability ratios (FRs) with 95% CIs representing the cycle-specific probability of conception by categories of age at menarche. FRs were adjusted for participants' pre-pregnancy body mass index, highest completed or ongoing education level, and age at initiation of trying to conceive. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a 7% lower probability of conceiving during any given menstrual cycle up to 12 cycles in women with early or late menarche. Among women with menarche >15 years, the adjusted FR was 0.93 (95% CI: 0.90-0.97), and among women with menarche <11 years, the adjusted FR was 0.93 (95% CI: 0.89-0.99), when compared to women with menarche between 12 and 14 years. LIMITATIONS, REASONS FOR CAUTION: The study-population consisted of women pregnant in their second trimester, excluding those with persistent infertility. Recall of age at menarche and time to pregnancy may be inaccurate. WIDER IMPLICATIONS OF THE FINDINGS: Both early (<11 years) and late (>15 years) menarche was associated with decreased fecundability. Women experiencing early menarche or late menarche may be counselled accordingly. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Norwegian Institute of Public Health, Oslo, Norway, and by Telemark Hospital Trust, Porsgrunn, Norway and was partly supported by the Research Council of Norway through its centres of excellence funding scheme (project number 262700) and the Research Council of Norway (project no. 320656). The project was co-funded by the European Union (ERC, BIOSFER, 101071773). Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible for them. M.C.M. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement no. 947684). The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Interpregnancy weight change and recurrence of gestational diabetes mellitus: a population-based cohort study.

OBJECTIVE: To estimate recurrence risk of gestational diabetes mellitus (GDM) by interpregnancy weight change. DESIGN: Population-based cohort study. SETTING AND POPULATION: Data from the Swedish (1992-2010) and the Norwegian (2006-2014) Medical Birth Registries on 2763 women with GDM in first pregnancy, registered with their first two singleton births and available information on height and weight. METHODS: Interpregnancy weight change (BMI in second pregnancy minus BMI in first pregnancy) was categorised in six groups by BMI units. Relative risks (RRs) of GDM recurrence were obtained by general linear models for the binary family and adjusted for confounders. Analyses were stratified by BMI in first pregnancy (<25 and ≥25 kg/m2 ). MAIN OUTCOME MEASURE: GDM in second pregnancy. RESULTS: Among overweight/obese women (BMI ≥25), recurrence risk of GDM decreased in women who reduced their BMI by 1-2 units (relative risk [RR] 0.80, 95% CI 0.65-0.99) and >2 units (RR 0.72, 95% CI 0.59-0.89) and increased if BMI increased by ≥4 units (RR 1.26, 95% CI 1.05-1.51) compared wth women with stable BMI (-1 to 1 units). In normal weight women (BMI <25), risk of GDM recurrence increased if BMI increased by 2-4 units (RR 1.32, 95% CI 1.08-1.60) and ≥4 units (RR 1.61, 95% CI 1.28-2.02) compared with women with stable BMI. CONCLUSION: Interpregnancy weight loss reduced risk of GDM recurrence in overweight/obese women. Weight gain between pregnancies increased recurrence risk for GDM in both normal and overweight/obese women. Our findings highlight the importance of weight management in the interconception window in women with a history of GDM. TWEETABLE ABSTRACT: Interpregnancy weight loss reduces recurrence of gestational diabetes mellitus in overweight/obese women.

Breastfeeding and long-term maternal metabolic health in the HUNT Study: a longitudinal population-based cohort study.

OBJECTIVE: Breastfeeding (BF) has been reported to improve long-term maternal metabolic health in observational studies, but not in the randomised controlled PROBIT study. Research also suggests that maternal pre-pregnant metabolic health may affect BF. We aimed to disentangle effects of BF on long-term maternal metabolic health from effects of pre-pregnant metabolic health on BF duration and long-term metabolic health. DESIGN: Longitudinal population-based cohort study. SETTING: Nord-Trøndelag county, Norway. POPULATION: Women with a first live-born baby (1987-2008) participating in the Nord-Trøndelag Health Study (HUNT). METHODS: Odds ratios (ORs) for short BF duration (<3 months) by pre-pregnant body mass index (BMI), waist circumference (WCF), blood pressures (BPs), and heart rate (HR) were adjusted for age and smoking using logistic regression. Mixed linear models were used to estimate effects of BF duration (<3, 3-6, >6 months) on mean values of metabolic health parameters from baseline to follow-up. MAIN OUTCOME MEASURES: Mean change in BMI, WCF, BPs, HR, serum-glucose, and serum-lipids from baseline to follow-up by BF duration categories. RESULTS: We analysed 1403 women with a median follow-up of 12 years (interquartile range 11-22). Pre-pregnant WCF and HR correlated inversely with BF duration. Pre-pregnant BMI had a u-shaped correlation-pattern with BF duration. We observed similar between-group differences in metabolic health parameters at baseline and at follow-up, which implies that mean change in metabolic health parameters was similar across BF groups. Those women who started out with the best health had the longest BF duration and ended up with the best health, and those women who started out with the poorest health had shortest BF duration and ended up with the poorest health. CONCLUSIONS: Our results do not support a causal relationship between long BF duration and improved metabolic health. It is more likely that pre-pregnant metabolic health affects both BF duration and long-term metabolic health. Reverse causality can explain previously observed improved long-term metabolic health after BF. TWEETABLE ABSTRACT: Breastfeeding seems not to affect long-term maternal metabolic health, but good pre-pregnant metabolic health does.

Offspring birthweight by gestational age and parental cardiovascular mortality: a population-based cohort study.

OBJECTIVE: To estimate risk of parental cardiovascular disease mortality by offspring birthweight. DESIGN: Population-based cohort study. SETTING AND POPULATION: Norwegian mothers and fathers with singleton births during 1967-2002 were followed until 2009 by linkage to the Norwegian cause of death registry. METHODS: Hazard ratios by offspring absolute birthweight in grams and birthweight adjusted for gestational age (z-score) were calculated using Cox regression and adjusted for parental age at delivery and year of first birth. Stratified analyses on preterm and term births were performed. MAIN OUTCOME MEASURES: Maternal and paternal cardiovascular mortality. RESULTS: We followed 711 726 mothers and 700 212 fathers and found a strong link between maternal cardiovascular mortality and offspring birthweight but only slight evidence of associations in fathers. Adjusting birthweight for gestational age (by z-score) uncovered an unexpected strong association of large birthweight (z-score > 2.5) with mothers' cardiovascular mortality (hazard ratio 3.0, 95% CI 2.0-4.6). This risk was apparently restricted to preterm births. In stratified analyses (preterm and term births) hazard ratios for maternal cardiovascular mortality were 1.5 (1.03-2.2) for large preterm babies and 0.9 (0.7-1.2) for large term babies (P-value for interaction = 0.02), using normal weight preterm and term, respectively, as references. CONCLUSION: Women having large preterm babies are at increased risk of both diabetes and cardiovascular mortality. The birth of a large preterm baby should increase clinical vigilance for onset of diabetes and other cardiovascular disease risk factors. TWEETABLE ABSTRACT: Birth of a large preterm baby should increase vigilance for cardiovascular-disease risk factors.

Gestational diabetes mellitus and interpregnancy weight change: A population-based cohort study.

BACKGROUND: Being overweight is an important risk factor for Gestational Diabetes Mellitus (GDM), but the underlying mechanisms are not understood. Weight change between pregnancies has been suggested to be an independent mechanism behind GDM. We assessed the risk for GDM in second pregnancy by change in Body Mass Index (BMI) from first to second pregnancy and whether BMI and gestational weight gain modified the risk. METHODS AND FINDINGS: In this observational cohort, we included 24,198 mothers and their 2 first pregnancies in data from the Medical Birth Registry of Norway (2006-2014). Weight change, defined as prepregnant BMI in second pregnancy minus prepregnant BMI in first pregnancy, was divided into 6 categories by units BMI (kilo/square meter). Relative risk (RR) estimates were obtained by general linear models for the binary family and adjusted for maternal age at second delivery, country of birth, education, smoking in pregnancy, interpregnancy interval, and year of second birth. Analyses were stratified by BMI (first pregnancy) and gestational weight gain (second pregnancy). Compared to women with stable BMI (-1 to 1), women who gained weight between pregnancies had higher risk of GDM-gaining 1 to 2 units: adjusted RR 2.0 (95% CI 1.5 to 2.7), 2 to 4 units: RR 2.6 (2.0 to 3.5), and ≥4 units: RR 5.4 (4.0 to 7.4). Risk increased significantly both for women with BMI below and above 25 at first pregnancy, although it increased more for the former group. A limitation in our study was the limited data on BMI in 2 pregnancies. CONCLUSIONS: The risk of GDM increased with increasing weight gain from first to second pregnancy, and more strongly among women with BMI < 25 in first pregnancy. Our results suggest weight change as a metabolic mechanism behind the increased risk of GDM, thus weight change should be acknowledged as an independent factor for screening GDM in clinical guidelines. Promoting healthy weight from preconception through the postpartum period should be a target.

Obstetric and neonatal outcome of pregnancies fathered by males on immunosuppression after solid organ transplantation.

Immunosuppressive drugs may influence spermatogenesis, but little is known about outcome of pregnancies fathered by transplanted males. We estimated risk of adverse outcomes in pregnancies (with data after the first trimester) fathered by males that had undergone organ transplantation and were treated with immunosuppression. A population-based study, linking data from the Norwegian transplant registry and the Medical Birth Registry of Norway during 1967-2009 was designed. All Norwegian men undergoing solid organ transplantation were included. Odds ratios for major malformations, preeclampsia, preterm delivery (<37 weeks) and small-for-gestational-age were obtained using logistic regression. A total of 2463 transplanted males, fathering babies of 4614 deliveries before and 474 deliveries after transplantation were identified. The risk of preeclampsia was increased (AOR: 7.4, 95% CI: 1.1-51.4,) after transplantation compared to prior to transplantation. No increased risk was found for congenital malformations or other outcomes when compared with pregnancies before transplantation or with the general population (2 511 506 births). Our results indicate an increased risk of preeclampsia mediated through the transplanted and immunosuppressed father. Importantly, no increased risk was found for other adverse obstetric outcomes or malformations, which may reassure male transplant recipients planning to father children.

Pre-pregnant body mass index and recreational physical activity: effects on perinatal mortality in a prospective pregnancy cohort.

OBJECTIVE: To examine the effect of maternal pre-pregnant body mass index (BMI) and recreational physical activity on perinatal mortality. DESIGN: A prospective cohort study. SETTING: The Norwegian Mother and Child Cohort (MoBa), 1999-2008. POPULATION: Singleton pregnancies without congenital anomalies (n = 77 246). METHODS: Pre-pregnant BMI was classified as underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9), obese (30-34.9) or morbidly obese (BMI ≥ 35). Risk estimates were obtained by logistic regression and adjusted for confounders. MAIN OUTCOME MEASURES: Perinatal death (stillbirth ≥ 22 weeks plus early neonatal death 0-7 days after birth). RESULTS: An increased risk of perinatal death was seen in obese [odds ratio (OR) 2.4, 95% CI (confidence interval) 1.7-3.4] and morbidly obese women (OR 3.3, 95% CI 2.1-5.1) as compared with normal weight women. In the group participating in recreational physical activity during pregnancy, obese women had an OR of 3.2 (95% CI 2.2-4.7) for perinatal death relative to non-obese women. In the non-active group the corresponding OR was 1.8 (95% CI 1.1-2.8) for obese women compared with non-obese women. The difference in perinatal mortality risk related to obesity between the active and non-active groups was statistically significant (P-value for interaction = 0.046, multiplicative model). CONCLUSIONS: Maternal obesity was associated with a two- to three-fold increased risk of perinatal death when compared with normal weight. For women with a BMI <30 the lowest perinatal mortality was seen in those performing recreational physical activity at least once a week.

Ultrasound prediction of perinatal outcome: the unrecognised value of sibling data.

OBJECTIVE: To identify high-risk fetuses at the first routinely performed ultrasound examination by making use of information from the mother's previous pregnancy. DESIGN: A population-based cohort study. SETTING: Norway, 1999-2009. POPULATION: All singleton first live births and their second-born siblings registered in the Medical Birth Registry of Norway (166,786 eligible sibling pairs). METHODS: Odds ratios were calculated by logistic regression. MAIN OUTCOME MEASURES: Very small for gestational age (vSGA; birthweight ≤-1.96 standard deviations) and perinatal death (stillbirth at ≥22 weeks of gestation or death within 28 days of life). RESULTS: Small fetal size at ultrasound (i.e. a fetus smaller than expected by last menstrual period, LMP) is only weakly predictive of vSGA or perinatal death; however, if the firstborn sibling was vSGA at birth, ultrasound measures in the next pregnancy become strongly informative of risk. The smaller the fetal size on ultrasound, the higher its risk of vSGA (3-18%; Ptrend < 0.0001) and perinatal death (4-19 per thousand, Ptrend = 0.012). In contrast, if the first baby was not vSGA, small fetal size on ultrasound is uninformative. CONCLUSIONS: When the firstborn baby is vSGA, discrepancies between fetal size on ultrasound and LMP become highly predictive of risk of vSGA and perinatal mortality in the second-born infant. The value of combining these routinely collected clinical data has not previously been recognised.

Availability and access in modern obstetric care: a retrospective population-based study.

OBJECTIVE: To assess the availability of obstetric institutions, the risk of unplanned delivery outside an institution and maternal morbidity in a national setting in which the number of institutions declined from 95 to 51 during 30 years. DESIGN: Retrospective population-based, three cohorts and two cross-sectional analyses. SETTING: Census data, Statistics Norway. The Medical Birth Registry of Norway from 1979 to 2009. POPULATION: Women (15-49 years), 2000 (n = 1,050,269) and 2010 (n = 1,127,665). Women who delivered during the period 1979-2009 (n = 1,807,714). METHODS: Geographic Information Systems software for travel zone calculations. Cross-table and multiple logistic regression analysis of change over time and regional differences. World Health Organization Emergency Obstetric and Newborn Care (EmOC) indicators. MAIN OUTCOME MEASURES: Proportion of women living outside the 1-hour travel zone to obstetric institutions. Risk of unplanned delivery outside obstetric institutions. Maternal morbidity. RESULTS: The proportion of women living outside the 1-hour zone for all obstetric institutions increased from 7.9% to 8.8% from 2000 to 2010 (relative risk, 1.1; 95% confidence interval, 1.11-1.12), and for emergency obstetric care from 11.0% to 12.1% (relative risk, 1.1; 95% confidence interval, 1.09-1.11). The risk of unplanned delivery outside institutions increased from 0.4% in 1979-83 to 0.7% in 2004-09 (adjusted odds ratio, 2.0; 95% confidence interval, 1.9-2.2). Maternal morbidity increased from 1.7% in 2000 to 2.2% in 2009 (adjusted odds ratio, 1.4; 95% confidence interval, 1.2-1.5) and the regional differences increased. CONCLUSIONS: The availability of and access to obstetric institutions was reduced and we did not observe the expected decrease in maternal morbidity following the centralisation.

Recurrence of prolonged and post-term gestational age across generations: maternal and paternal contribution.

OBJECTIVE: To estimate intergenerational recurrence risk of prolonged and post-term gestational age. DESIGN: Population-based cohort study. SETTING: Norway, 1967-2006. POPULATION: Intergenerational data from the Medical Birth Registry of Norway of singleton mothers and fathers giving birth to singleton children: 478 627 mother-child units and 353 164 father-child units. A combined mother-father-child file including 295 455 trios was also used. METHODS: Relative risks were obtained from contingency tables and relative risk modelling. MAIN OUTCOME MEASURES: Gestational age ≥41 weeks (≥287 days), ≥42 weeks (≥294 days) and ≥43 weeks (≥301 days) of gestation in the second generation. RESULTS: A post-term mother (≥42 weeks) had a 49% increased risk of giving birth to a child at ≥42 weeks (relative risk [RR] 1.49, 95% CI 1.47-1.51) and a post-term father had a 23% increased risk of fathering a child at ≥42 weeks (RR 1.23, 95%CI 1.20-1.25). The RRs for delivery at ≥41 weeks were 1.29 (1.28-1.30) and 1.14 (1.13-1.16) for mother and father, respectively, and for ≥43 weeks 1.55 (1.50-1.59) and 1.22 (1.17-1.27). The RR of a pregnancy at ≥42 weeks in the second generation was 1.76 (1.68-1.84) if both mother and father were born post-term. Adjustment for maternal age in both generations, fetal sex in the second generation, parity, and maternal and paternal birthweight did not influence the risk estimates. CONCLUSIONS: There is a familial factor related to recurrence of prolonged pregnancy across generations and both mother and father seem to contribute.

Placenta percreta--two cases and review of the literature.

Two cases of placenta pecreta confirmed histologically were treated conservatively with retention of the uterus. Both later went on to have successful pregnancies.