Reference

Study type

Characteristics

Intervention (I)

Controls (C)

Outcome measures and follow-up time

Results

Quality

assessment study

Berends, 2008

Design

Case-control study

N total = 212

Aim of the study

to provide biochemical and anthropometric

evidence to substantiate the hypothesis that cardiovascular

risk factors are constitutional in women with a history of

pregnancies complicated by preeclampsia or IUGR.

Inclusion criteria

- preeclampsia

- IUGR

- singletons

Exclusion criteria

- pregnant

- postmenopausal

- DM

- Lipid-lowering or antihypertensive medication use

Preeclampsia

N = 50

IUGR (≤p5)

N = 56

Uncomplicated pregnancies

N = 106

Primary outcomes:

anthropometrics, lipids, glucose levels, blood pressure measurements, and IMT

Secundary outcomes:

Follow up:

Time interval delivery – study, mean, y

Preeclampsia 7 (±5.6)

IUGR 9.3 (±4.6)

Controls 13.1 (±5.7)

Primary outcomes:

Diagnosis of hypertension was 5 times more common in formerly preeclamptic women compared with control subjects (46.7% versus 8.9%; P<0.001) and 3 times in women with IUGR-complicated pregnancies (26.9% versus 8.9%; P<0.01).

Secundary outcomes:

Clearly defined groups:

IUGR was defined as birth weight of newborns equal to or below the fifth percentile, according to the Dutch fetal growth charts of Kloosterman

Selection bias:

Possible, small numbers

Method of assessing the outcome

appropriately:

Yes, women with a history of preeclampsia or a pregnancy complicated by IUGR were selected from the Genetic Research in Isolated Populations population. If preeclampsia and IUGR co-occurred (n=8), women were categorized in the preeclampsia Group. Diagnoses were confirmed

by the research physician after reviewing the medical charts. Control subjects and their parents were recruited from participants of the Erasmus Rucphen Family. Hypertension was defined as diastolic blood pressure ≥90 mm Hg, and/or a systolic blood pressure ≥140 mm Hg, and/or use of antihypertensive medication

Selective loss to follow up:

No

Identification confounders and correction in analysis:

Yes

Funding:

This study was sponsored by an Erasmus University Medical Center grant and the Center for Medical Systems Biology

Bonamy, 2011

Design

Retrospective cohort study

N total =

923 686

Aim of the study

To investigate the hypothesis that maternal risks of CVD increase both with severity of prematurity and fetal growth restriction.

Inclusion criteria

1. All women having a first singleton delivery from 1983-2005

Exclusion criteria

1. Immigrating women

2. CVD-event before first child

3. Missing information on GA or birth weight.

Intervention

Birth weight very small (<2SD)

N = 27 806

Controls

Normal birth weight (±1 SD)

N = 530 449

Primary outcomes:

First CVD event (coronary heart disease (CHD), cerebrovascular

events, or heart failure)

Secundary outcomes:

Follow up:

End of follow-up

was December 31, 2005, or the date of first occurrence of the following: first CVD event (as defined below), emigration from

Sweden, or death. Median follow-up time 11.8 years (0-23.0 years)

Primary outcomes:

Secundary outcomes:

Clearly defined groups:

Yes

Selection bias:

Possible, retrospective cohort study. But not expected

Method of assessing the outcome

appropriately:

Yes, they accessed data from population-based registers maintained at the Swedish National Board of Health and Welfare and Statistics.

Individual records were linked across registers using the unique personal identity number assigned to all Swedish residents.  Birth weight for gestational age was based on the Swedish

reference curve for intrauterine growth and was defined as the ratio of observed to expected birth weight with regard to gestational age and sex. A normal birth weight ratio was defined as 0.90 to 1.09(approximately between 1 SD above the mean to 1 SD below the mean), very small as <0.75 (approximately 2 SD below the mean), moderately small as 0.75 to 0.89 (approximately between 1 and 2 SD below the mean)

Sweden, or death.

Incidence in CVD was defined as the first hospitalization (assessed from the Hospital Discharge Register) or death (assessed from the Cause of Death Register) caused by coronary heart disease (CHD), cerebrovascular events, or heart failure. Coronary heart disease was defined as

unstable angina (ICD-8 code 411, ICD-9 code 411B, ICD-10 code I20.0) or acute myocardial infarction (ICD-8 and ICD-9 code 410,

ICD-10 codes I21-I22). Cerebrovascular events were defined as cerebral infarction (ICD-8 codes 432–434, ICD-9 codes 433–434, ICD-10 code

I63), cerebral hemorrhage (ICD-8 code 431, ICD-9 codes 431–432, ICD-10 codes I61-I62), subarachnoid hemorrhage (ICD-8 and ICD-9

code 430, ICD-10 code I60), transient ischemic attack (ICD-8 and ICD-9 code 435, ICD-10 code G45), or other acute stroke (ICD-8 and

ICD-9 code 436, ICD-10 code I64). Heart failure was defined by ICD-8codes 427.00 and 427.10, ICD-9 code 428, ICD-10 code I50.

Selective loss to follow up:

No

Identification confounders and correction in analysis:

Yes, adjustment maternal age, birth year, highest income, and education levels before first delivery, country of birth, pregestational diabetes mellitus, pregestational hypertension, gestational diabetes mellitus, gestational hypertension, and preeclampsia/eclampsia and smoking.

Funding:

Yes, Foundation of National Board

of Health and Welfare, the Swedish Society for Medical Research, the Swedish Research Council, and the Swedish Council for Working

Life and Social Research.

Bukowski, 2012

Design

Cross-sectional study

N total =

6608

Aim of the study

to investigate the

association between delivery of a SGA infant and maternal risk for IHD in relation to traditional IHD risk factors.

Inclusion criteria

- women from NHANES study, period 1999-2006

- live term birth

Exclusion criteria

SGA (≥37 wks and <2500 g)

N = 309

No SGA

N = 6299

Primary outcomes:

IHD (coronary heart disease, angina pectoris or myocardial infarction)

Secundary outcomes:

IHD risk factors

Follow up:

?

Primary outcomes:

- Among 6,608 women in this study 453 had IHD.

- In a fully adjusted model, accounting for all studied IHD

risk factors, SGA and family history , the risk of IHD associated

with delivery of a SGA infant did not change appreciably either

(risk factors adjusted OR; 95% CI: 1.7; 1.1, 2.8; p= 0.022).

Secundary outcomes:

- There was no evidence of association of SGA with traditional

IHD risk factors except for smoking. The age adjusted odds of

hypertension (1.3; 0.9, 1.9; p =0.2), diabetes (0.8; 0.5–1.4; p = 0.4),

elevated total and LDL cholesterol concentrations (1.1; 0.8, 1.7;

p = 0.5 and 1.02; 0.6, 1.8; p = 0.9, respectively) were not

significantly associated with giving birth to SGA infant. SGA

was associated with significantly higher age adjusted odds of

smoking (1.4; 1.04, 1.9; p = 0.028).

- The median time interval from last delivery to

occurrence of IHD was 30 (interquartile range: 20, 36) years. The

time interval from last delivery to occurrence of IHD was not

significantly different between women with and without SGA

infant (median; interquartile range: 29; 20–35 and 30; 20–39;

respectively p = 0.3).

Clearly defined groups:

Yes

Selection bias:

Possible, SGA was self-reported.

Method of assessing the outcome

appropriately:

The National Health and Nutrition Examination Survey (NHANES) is a nationally representative complex-sample survey of the U.S. population, designed to provide an estimate of the health status in the general population. Delivery of a SGA infant and diagnosis of first IHD event were self-reported. Risk factors for IHD were documented or measured at the time of NHANES examination. IHD included coronary heart disease, angina pectoris or myocardial infarction diagnosed by a physician or health professional and reported by participants. Mortality follow-up data from the date of survey participation through December 31, 2006 were obtained from the NHANES

Linked Mortality Files linking NHANES data with death certificate data found in the National Death Index.

Selective loss to follow up:

No

Identification confounders and correction in analysis:

Yes

Funding:

No funding

Limitations

- cross-sectional design, which generally is not well suited for causative inferences because of lack of information on sequence of events and possibility of incidence-prevalence bias.

- The retrospective assessment of birth weight could also potentially be subject to bias

Catov, 2007

Design

Case-cohort

N total = 446

Aim of the study

We investigated whether older women who delivered LBW infants had higher blood

pressure, lipid, glucose, insulin, interleukin 6 (IL-6), and C-reactive protein concentrations, and pulse

wave velocity compared to women with normal-weight births.

Inclusion criteria

- Participants of the Health, Aging, and Body Composition Study (USA)

- age of 70 to 79 years, self-report of no difficulty

walking one quarter mile or climbing 10 steps

without resting, no difficulty performing basic activities of

daily living, no use of assistive devices to ambulate, no history

of active treatment for cancer in the prior 3 years, and

no plans to move out of the area in the next 3 years.

Exclusion criteria

- women who reported hypertension during pregnancy (n =11; 2.4%) or preeclampsia (n = 11; 2.4%)

Intervention

Women delivered a first-birth infant <2500 gr

N = 56

Controls

Women delivered a first-birth infant ≥2500 gr

N = 390

Primary outcomes:

The primary end points were cardiovascular risk factors assessed

at baseline (1997 to 1998): Blood pressure, lipid, glucose, insulin, interleukin 6 (IL-6), and C-reactive protein concentrations, and pulse wave velocity

Secundary outcomes:

Follow up:

Not applicable

Primary outcomes:

Secundary outcomes:

Clearly defined groups:

Yes

Selection bias:

Not expected, maybe recall bias

Method of assessing the outcome

appropriately:

Yes, women reported birth weight and complications for each pregnancy. Analysis was limited to first births not complicated by

hypertension or preeclampsia.

Selective loss to follow up:

No

Identification confounders and correction in analysis:

BMI, age and race

Funding:

This study was supported by contracts N01-AG-6-2101, N01-AG-6- 2103, and N01-AG-6-2106.

Catov 2011

Design

Case-cohort

N total = 679

Aim of the study

To estimate whether women who deliver small babies due to preterm birth or growth restriction have excess risk for cardiovascular disease and diabetes later in life.

Inclusion criteria

- women who gave birth between 1997 and 2002 at Magee-Womens Hospital in Pittsburgh, Pennsylvania

Exclusion criteria

- Women with preeclampsia or prepregnancy diabetes or hypertension

Intervention

Women with prior SGA (<p5)

N = 106

Women with preterm birth (GA <37 wk)

N = 181

Controls

Women with term birth and birthweight >p10

N = 306

Primary outcomes:

- metabool syndroom

Secundary outcomes:

Follow up:

Not applicable

Primary outcomes:

Secundary outcomes:

Clearly defined groups:

Yes

Selection bias:

Not expected

Method of assessing the outcome

appropriately:

The Women and Infant Study of Healthy Hearts is a cohort study of cardiovascular risk factors assessed among women 4 to 12 years after delivery of singleton infants who were preterm, small for gestational age, or term non-SGA.

Eight years after pregnancy women underwent a structured interview and fasting blood sampling.

Women with infants that were both preterm and SGA (n=9) were analyzed with the preterm group.

Selective loss to follow up:

Of the 4,908 eligible women identified via a hospital electronic birth registry, 1,569 (32%) were able to be located via mail or phone and were screened. Of those screened, 702 women (45%) provided informed consent and were enrolled.

Identification confounders and correction in analysis:

socioeconomic status cluster (age at baseline, age at index birth, race, education, income), body size cluster (body mass index and weight at baseline), and smoking cluster (smoking during pregnancy _yes or no_, amount smoked during

pregnancy, current or not current smoking, ever smoking _yes or no_, number of cigarettes smoked, number of years smoked

_among ever smokers_).

Funding:

Supported by National Institutes of Health grants R01HL076532 and K12 HD043441.

Kanagalingam, 2009

Design

Case-control

N total = 57

Aim of the study

Case control study with analysis of inflammatory, lipid, metabolic and haemostatic markers and

microvascular function as assessed by laser Doppler iontophoresis 4 years after the index pregnancy

Inclusion criteria

Women who previously delivered at Princess

Royal Maternity Hospital a first child with a birthweight below the 5th centile at 36–43 weeks gestation

Exclusion criteria

- CRP > 10 mg/l à subclinical infection/inflammation which may have influenced lipid, insulin and microvascular function.

- no history of obstetric or metabolic disease

prior to the index pregnancy

- the index pregnancy ended in a stillbirth, if there

were clinical signs of pre-existing hypertension or pre-eclampsia or pregnancy-induced hypertension according to the International

Society for the Study of Hypertension in Pregnancy (ISSHP) definition

- mother or offspring with genetic or anatomical anomaly that were likely to contribute to reduced fetal growth

- ongoing pregnancy, pregnancy within the last

6 months, current breast feeding and insulin dependent diabetes.

Women delivered a first child below the 5^th centile

N = 28

Women delivered a first child

between the 25th and 90th centile

N = 29

Primary outcomes:

- inflammatory markers

- lipid markers

- metabolic markers

- haemostatic markers

- microvascular function by laser Doppler iontophoresis

Secundary outcomes:

Follow up:

1-5  years from index pregnancy

Primary outcomes:

In absolute terms CRP, IL-6 and ICAM-1 were higher in mothers who had SGA offspring. Significant perturbation of lipid parameters was also observed, with triglyceride, VLDL-cholesterol, LDLcholesterol: HDL-cholesterol ratio and cholesterol:HDL-cholesterol ratio all higher in mothers with SGA offspring.

Secundary outcomes:

Clearly defined groups:

Yes

Selection bias:

Possible, case-control study

Method of assessing the outcome

appropriately:

Yes

Selective loss to follow up:

No

Identification confounders and correction in analysis:

Adjustment for age, BMI, DEPCAT group, smoking status, height, contraception use and parity.

Funding:

Chest Heart Stroke Association

Li, 2010

Design

Retrospective cohort study

N total =

1 400 383

Aim of the study

To investigate the association between offspring birth

weight and parental CVD mortality.

Inclusion criteria

- primigravida, singletons in Taiwan between 1978 and 1987

Exclusion criteria

- missing information

on gestational age or with a gestational age > 42 weeks.

Intervention

SGA (<p10)

N = 167 205

Controls

AGA (p10-90)

N = 1 146 774

Primary outcomes:

Parental cardiovascular mortality

Secundary outcomes:

Follow up:

23.94

Primary outcomes:

Secundary outcomes:

Clearly defined groups:

Yes

Selection bias:

Not expected

Method of assessing the outcome

appropriately:

Yes, Mortality data were obtained from the Taiwan Death Registry (TDR) for the period from 1978 to 2006 (ICD-9-CM mortalities included the following: CVD (401–405, 410–414, 415–417 and 420–429), stroke (430–438), all circulatory disease (390–459))

Selective loss to follow up:

No

Identification confounders and correction in analysis:

Yes, adjusted for year of offspring birth, urbanization of residential area

and parental ages, education levels, employment status and marital status at the time of offspring birth.

Funding:

This work was supported by a grant from the National Scientific Council of Taiwan. (NSC NSC98-2314-B- 227-001-MY2).

Lykke, 2010

Design

Retrospective cohort study

N total = 782 287

Aim of the study

To elucidate the impact of

preterm delivery, delivery of an SGA offspring,

hypertensive disorders of pregnancy, placental abruption and stillbirth in a first delivery on subsequent rates of death from cardiovascular and noncardiovascular and all causes.

Inclusion criteria

1. Women delivering in Denmark from 1978 – 2007.

2. 15-50 years

3. First singelton delivery.

Exclusion criteria

1. any preceding cardiovascular diagnosis (e.g.hypertension or deep venous thromboembolism.

2. DM

3. Died or emigrate within 3 months of delivery.

Intervention

SGA: fetal growth ≥ 2 SD below mean

N = 33 311

Controls

Appropriate-for-gestational-age (AGA):  < 2 SD below or above mean

N = 643 935

Primary outcomes:

Death from all causes, which

was also subdivided into death from cardiovascular

causes and non-cardiovascular causes.

Secundary outcomes:

Follow up:

Median 14.63 years (-.25-30.1):

Primary outcomes:

Secondary outcomes:

Hypertension

'DI10' 'DI11' 'DI12' 'DI13' 'DI15'

'400' '401' '402' '403' '404'

Ischemic heart disease

'DI20' 'DI21' 'DI22' 'DI23' 'DI24' 'DI25' '410' '411' '412' '413' '414'

Myocardial diseases

'DI50' 'DI513' 'DI519'

'42709' '42710' '42711' '42719' '42799' '42899' '42900' '42908' '42909'

Vascular diseases of the CNS (stroke)

'DI60' 'DI61' 'DI62' 'DI63' 'DI64' 'DI65' 'DI66' 'DI67' 'DG45'

'430' '431' '432' '433' '434' '435' '436 '437' '438'

Thromboembolic diseases

'DI26' 'DI74' 'DI82' '444' '450' '451'

Type 2 diabtes mellitus

'DE11' 'DE12' 'DE13' 'DE14' '250'

Clearly defined groups:

Yes

Selection bias:

Possible, no confounding for moking,

obesity and socio-economic status and the questionable validity of the exposures and end points: the ICD codes of the hypertensive disorders of pregnancy have been assessed to be very specific, but only moderately sensitive,

with PPVs ranging from 56% to 100%.

Method of assessing the outcome

appropriately:

Yes, they extract information from the National Patient Registry (NPR) and used ICD codes for the primary outcome. The NPR collects information on all discharge diagnoses from hospitals and deliveries in Denmark.

Missing values occurred more frequently in the earlier years; these were analysed as separate groups.

When investigating combinations of preterm delivery,SGA and pre-eclampsia, they dichotomised hypertensive disorders of pregnancy into two groups: pre-eclampsia and no-pre-eclampsia (the latter being the reference group, which included gestational hypertension).

We restrictively defined a cardiovascular cause of death as either stated thus in the Cause of Death Registry, or a first cardiovascular diagnosis, e.g. de novo hypertension or ischaemic heart disease, reported within 1 week prior to the time of death.

Selective loss to follow up:

They censored women who had emigrated at the time of departure: n=15 902 (2%)

Identification confounders and correction in analysis:

Adjustment for maternal age at delivery

and year of delivery.

Funding:

None

Lykke 2012

Design

Retrospectivecohort study

N total =

782 287

Aim of the study

To investigate the relation between the standardized birthweight by gestational age and gender and the ponderal index and the mother’s subsequent mortality and cardiovascular morbidity.

Inclusion criteria

- All singleton deliveries in Denmark from ’78 up to ‘07

- Age at delivery: 15-50 yr

Exclusion criteria

- any cardiovascular diagnosis

- diabetes mellitus

- deceased

- emigrated within 3 months of delivery

Intervention

Birthweight

-2.0 – -3.0 SD

N = 33 366

Birthweight

< -3.0 SD

N = 6447

Controls

Birthweight

 -0.5 – +0.5 SD

N = 266 178

Primary outcomes:

Maternal death, first registered diagnosis of hypertension, IHD, stroke, thrombosis, diabetes

(ICD-8 and -10 codes)

Secundary outcomes:

Follow up:

14.6 years (range 0.25–30.2 years)

Primary outcomes:

Secundary outcomes:

For the women where smoking status was available (n=455 201, corresponding to 58% of the total population), smoking was associated with lower fetal growth, both birthweight and ponderal index. Women for whom information on smoking was not recorded had higher rates of later hypertension (14.4/10 000 person-years) comparedwith both non-smokers (11.8/10 000 person-years) and smokers (11.2/10 000 person-years). Women producing offspring with a low standardized birthweight and who were smokers had a lower risk of later hypertension, in comparison with non-smokers, whereas this differencewas not seen forwomen with high standardized birthweight. However, this effect was effaced when other pregnancy complications were adjusted for.

Clearly defined groups:

Yes

Selection bias:

Not expected

Method of assessing the outcome

appropriately:

For standardized birthweight we used a Scandinavian idealized distribution based on intrauterine measurements.

Selective loss to follow up:

During this follow-up period, 15 902 (2.0%) emigrated and 8 876 (1.1%) died.

Identification confounders and correction in analysis:

Adjustment for maternal age and year of delivery

gestational age, hypertensive pregnancy disorders, placental abruption, and stillbirth.

Funding:

No specific funding.

Manor, 2010

Design

Retrospective cohort study

N total =

14 129

Aim of the study

To examine the

association between infants’ birth weight and mortality

in their parents and grandparents using the

Uppsala Birth Cohort Multigenerational Study.

Inclusion criteria

- infants who were third-generation (G3) singleton descendants of the

Uppsala Birth Cohort (UBCoS), Sweden.

- Mothers born in 1932 or later

- Mothers who survived to at least 1961

Exclusion criteria

- Grandchildren born before 1973

- Twins

- Missing data on size at birth or length of gestation

- born at <30 weeks of gestation

Intervention

Birthweight <p5

N = NA

Controls

Birthweight p26-75

N = NA

Primary outcomes:

All-cause mortality and cardiovascular mortality (International Classification of

Diseases (ICD) 7: 330–334 and 400–468; 8 and

9:390–459; 10: I00–99)

Secundary outcomes:

Follow up:

22.0

Primary outcomes:

Secundary outcomes:

Clearly defined groups:

Yes

Selection bias:

Not expected

Method of assessing the outcome

appropriately:

The cohort was created by linking data from the Swedish Multigenerational Register, Medical Birth Registry, Hospital Discharge Register and Cause of Death Register on members of families originating from a cohort of 14 193 live births in the Uppsala University Hospital, Sweden, during 1915–29, of whom 12 168 were alive and residents of Sweden in 1947.

Selective loss to follow up:

Of the total number of 36 637 biological grandchildren (G3) of the UBCoS cohort, we excluded 7792 (21.3%) children who were born before 1973 (when the  Swedish Medical Birth Registry was established) and who thus did

not have data on size at birth. Of the 28 845

biological grandchildren born in the period 1973–

2002, we excluded an additional 643 (2.2%) who

were twins, 129 (0.4%) who had missing data on

size at birth or length of gestation in the Medical

Birth Register and 62 (0.2 %) who were born at

<30 completed weeks of gestation.

Identification confounders and correction in analysis:

Adjusted for age, period and parent’s education and parity.

Funding:

The UBCoS and UBCoS Multigen study has received grants from the UK Medical Research Council, the Swedish Research Council and the Swedish Council for Working Life and Social Research. I.K. is currentlyfunded by the Swedish Council for Working Life and Social Research.

Manten 2007

Design

Case-control study

N total = 112

Aim of the study

To investigate if women with a history of preeclampsia

or IUGR exhibit more risk factors for cardiovascular disease than do

women with previous uneventful pregnancies.

Inclusion criteria

- Study population: women with a history of early-onset preeclampsia or IUGR, necessitating delivery before 34 weeks of pregnancy at the University Medical Center Utrecht, The Netherlands.

- Controls: women with a history of uncomplicated pregnancy with normal course and outcome

Exclusion criteria

Intervention

SGA (<p5) and delivery because of signs of fetal distress before 34 wk of gestation.

N = 59

PE

N = 256

Controls

Uncomplicated pregnancy

N = 53

Primary outcomes:

blood pressure, body mass index, concentrations of cholesterol,

high-density lipoprotein cholesterol, triglycerides and lipoprotein (a), and

insulin resistance.

Secundary outcomes:

Follow up:

NA

Primary outcomes:

In the IUGR group there were 5 women (8%) with chronic hypertension of whom 4 (80%) required anti-hypertensive medication before pregnancy.

Secundary outcomes:

Subgroups of multiparous women with or without recurrent preeclampsia or IUGR was performed. Our group of women with a history of preeclampsia included 53 multiparous women, of which 18 had recurrent preeclampsia. In our group of women

with a history of IUGR there were 26 multiparous women of which 11 had recurrent IUGR. Analysis of these data revealed only one statistically significant difference: a higher blood pressure in multiparous women with nonrecurrent preeclampsia compared with the multiparous controls

NB: the preeclampsia group included women with or without

the HELLP-syndrome and women with or without IUGR infants. Since analysis of the data for these different subgroups did not yield different results, all patients with preeclampsia were combined to one single preeclampsia group.

- All women were of Caucasian origin.

Clearly defined groups:

Yes, preeclampsia was defined as two repeated (4 hours apart) diastolic blood pressure measurements of 90 mm Hg or greater and the presence of proteinuria (≥300 mg/24 h), in the absence of urinary tract infection or renal disease,

occurring after 20 weeks of gestation in a previously normotensive woman. In patients with chronic hypertension, preeclampsia was diagnosed

when de novo proteinuria (≥300 mg/24 h) occurred in the second half of pregnancy. HELLP-syndrome was defined as a platelet count < 100 × 109/L, an amino aspartate transferase concentration > 70 U/L and a lactate dehydrogenase concentration > 600 U/L.

IUGR was defined as a birth weight below the fifth percentile for the Dutch population, and a delivery because of signs of fetal distress before

34 weeks of gestation.

Selection bias:

Not expected, but control group is poorly defined, how were they recruited?

Method of assessing the outcome

appropriately:

- women were studied at least 3 months after delivery, and after ending lactation.

- All blood samples were drawn after an overnight fast

Selective loss to follow up:

Not applicable

Identification confounders and correction in analysis:

Yes, exclusion of women with fasting glucose concentrations ≥ 7.0 mmol/L

Funding:

Not reported

Mongraw 2010

Design

Cohort study

N = 14 403

Country

USA

Aim of the study:

This study prospectively investigates the contribution of pregnancy complications and other reproductive age

risk factors on the risk of subsequent cardiovascular disease death.

Inclusion criteria

- women partcipating in the Child Health

and Development Studies pregnancy cohort drawn from the Kaiser Permanente Health Plan in California with nonmissing parity and no previously diagnosed heart conditions

Exclusion criteria

- multiple birth pregnancies and

pregnancies missing on parity. We also excluded all of the pregnancies

that ended in abortion or fetal death before 20 weeks’ gestation

and women with pre-existing heart conditions diagnosed before

enrollment.

Intervention

IUGR (<p10)

N = not applicable

Controls

No PE and IUGR

N = not applicable

Primary outcomes:

CVD mortality

Secundary outcomes:

Follow up:

37 years

Primary outcomes:

Clearly defined groups:

Proteinuria is defined as a reading of +1 (0.5% or 300 mg/24 hours) on a urine dipstick. PE is defined as either of the following occurring after 20 weeks of gestation: ≥2 blood pressure readings ≥140/90 mm Hg and proteinuria or ≥2

systolic readings ≥140 mm Hg or ≥2 diastolic readings of ≥90 mm Hg and proteinuria. Preexisting hypertension was defined as ≥1 blood pressure reading of ≥140/90 mm Hg before 20 weeks of pregnancy or doctor-diagnosed hypertension from the medical chart. Gestational hypertension was defined as +1 blood pressure reading of ≥140/90 mm Hg that developed after the 20th week of pregnancy and not accompanied by proteinuria. Early onset PE was defined as onset of PE before 34 weeks of

gestation. IUGR was defined as below the 10th percentile of z scores in birth weight by sex and gestational age for the CHDS distribution.

Selection bias:

Not expected

Method of assessing the outcome

appropriately:

Cardiovascular disease death was determined by linkage with the California Department of Vital Statistics. CVD death,

including the following: 420.1 for ICD-7; 410 and 412 for ICD-8; 410, 411, 414, and 429 for ICD-9, and I21 to I25 for ICD-10.

Selective loss to follow up:

Not included in analysis

Identification confounders and correction in analysis:

Yes, not well described (The full model

was constructed using all of the variables of interest that were either independently significant and/or confounders to the 10% level after mutual adjustment)

Funding:

This project was made possible by funding from the National Institutes of Health (grant N01 DK63422).

Nilsson, 2009

Design

Retrospective cohort (population based)

N total =

1.4 million mothers and

2.7 million children.

Aim of the study

To investigate the risk of small for gestational age (SGA) births in relation to maternal history of

cardiovascular disease (CVD) across two generations and additionally to analyse maternal CVD risk

based on number of SGA offspring.

Inclusion criteria

- 1973 – 2004

Exclusion criteria

Intervention

SGA: birth weight 2 SD below mean

1 x SGA

N = 69 893

2 x SGA

N = 5658

≥3 x SGA

N = 504

Controls

No SGA offspring

N = 1 345 374

Primary outcomes:

- risk of being SGA in relation to maternal total CVD

Secundary outcomes:

- the risk of maternal

CVD based on number of SGA births.

Follow up:

Mean of 20 yrs

Primary outcomes:

- There were 10 436 fatal and non-fatal cardiovascular events

registered during the study period.

- When no family history of CVDin mothers was used as the

reference category, we found an overall HR of 1.11 (95% CI

1.09–1.13) of being SGA in female offspring for a positive

maternal history of CVD. The highest risk was found in

daughters when both the mother and the grandmother had

a history of CVD (HR 1.32, 95% CI 1.24–1.39).

The corresponding HR for SGA birth in male offspring

was 1.12 (95% CI 1.09–1.14) for a positive maternal history

of CVD, and 1.43 (95% CI 1.35–1.51) for CVD in two

generations

Secundary outcomes:

When ‘no SGA offspring’ was used as the reference category,

an increased number of CHD events was seen in mothers

in relation to the number of offspring born SGA. A stepwise

increase in risk was seen for increasing number of SGA

offspring (one: HR 1.93, 95% CI 1.76–2.12; two: HR 2.60,

95% CI 1.99–3.39; and three or more: HR 4.27, 95% CI

2.13–8.54; Table 3).

Clearly defined groups:

Yes

Selection bias:

No

Method of assessing the outcome

appropriately:

Database contains information on all pregnancies, prenatal care and births in Sweden between 1973 and 2004. This register covers 99% of all births

in Sweden since 1973 and includes prospectively collected information about complications during pregnancy and delivery.

ICD codes: for fatal or non-fatal CVD and coronary heart disease (CHD) from the start of the respective registers on a national basis: CVD: ICD-9, 390–459, ICD-10, I00–I99; CHD: ICD-9, 410–414, ICD-10, I20–I25.

Selective loss to follow up:

No

Identification confounders and correction in analysis:

socioeconomic status (occupation), education

level, age, time period and region of residence within Sweden

Funding:

This work was supported by a grant to Jan Sundquist from the National Institute of Child Health and Human Development

(NICHD), 1R01HD052848-01, and grants to Jan

and Kristina Sundquist from the Swedish Research Council (2008-3110 and 2008-2638), the Swedish Council for Working Life and Social Research (2006-0386, 2007-1754 and 2007–1962), the Swedish Research Council Formas (2006-4255-6596-99 and 2007-1352) and ALF project grant,

Stockholm, Sweden.

Wikstrom 2005

Design

Cohort study

N total = 403 550

Aim of the study

to investigate whether the risk of developing ischaemic heart disease (IHD) later in life increases with severity and recurrence of gestational hypertensive disease.

Inclusion criteria

- Women giving birth to their first child in Sweden, 1973–1982

Exclusion criteria

- Women with diabetes mellitus or essential hypertension

Intervention

Only SGA (<-2SD)

N = 12 432

Hypertensive disease

N = 20 469

Controls

Uncomplicated pregnancy

N = 347 870

Primary outcomes:

Fatal or non-fatal IHD

Secundary outcomes:

Follow up:

follow up was restricted to the period 1987–2001. The first admission to hospital with IHD as the main diagnosis, or death with IHD as the underlying cause, was designated the event.

Mean follow-up for SGA: 182,348 person-years

Primary outcomes:

Secundary outcomes:

Clearly defined groups:

Yes, pre-eclampsia was defined as a rise in blood pressure (≥140/90) combined with proteinuria

(≥300 mg/24 hours). Severe pre-eclampsia was defined as pre-eclampsia with either a diastolic blood pressure of at least 110 mmHg, or proteinuria of at least 5 g/24 hours, or both. Gestational hypertension was defined as a rise in

blood pressure (≥140/90) occurring after 20 weeks of gestation without proteinuria. preterm delivery was defined as occurring before 37 weeks of gestation. SGA was defined as birthweight

<2 SDs below the mean birthweight for gestational age.

Selection bias:

Not expected

Method of assessing the outcome

appropriately:

Information from the Swedish Medical Birth Register, for the period 1973–1982, was used to define the study population. Complications during pregnancy and delivery are classified according to the Swedish version of the International

Classification of Diseases (ICD)

Selective loss to follow up:

Before 1987, 0.35% of the para-1 cohort had

died and 2.8% had emigrated

Identification confounders and correction in analysis:

They onsidered age, hospital at delivery and socioeconomic status to be possible confounders.

Funding:

Not reported

Tabel 4.6.2: risico’s op het ontwikkelen van hypertensie (HT)bij vrouwen die eengroeibeperkt kind

hebben gehad ten opzichte van vrouwen die een ongecompliceerde zwangerschap hebben doorgemaakt

Studie

Definitie SGA

N

Gem FU (jr)

Gem lft FU (jr)

Definitie HT

Aantal met HT (N)

Gecorrigeerde risico’s (95% BI)

Gecorrigeerd voor

A

NA

A

NA

A

NA

Cohort onderzoeken waarin vrouwen met een groeibeperkt kind zijn vergeleken met vrouwen zonder groeibeperkt kind

Lykke

2012

-2.0 – -3.0

SD

33 366

266 178

14.6

~41

V

1249

5302

HR 1.24 (1.16-1.32)

Lft, jaar van bevalling,

hypertensieve aandoening zwangerschap,

vroeggeboorte, abruptio placentae, IUVD

< -3.0 SD

6447

342

HR 1.20 (1.06-1.34)

Onderzoeken met patiënten series waarin vrouwen met een groeibeperkt kind zijn vergeleken met vrouwen zonder groeibeperkt kind

Berends, 2008

≤p5

56

106

9.3

39

39.2

II, III, IV

15

9

OR 3.15 (1.47-6.75)

Geen

Catov, 2011

<p10

192

304

8

37.3

36.5

III, IV

10

15

OR 1.39 (0.60-2.98)

Lft, ras, opleiding, inkomen, BMI, roken

Afkortingen: A = aangedaan door ziektebeeld;  B = beroerte; BI =  beroerte, ischemisch;

BH = beroerte, hemorragisch; BMI = body mass index;   DM = diabetes mellitus;  DR = dysritmie;

F = fataal; FU = follow-up; GDM = diabetes gravidarum; HT = hypertensie; CV gebeurtenis = hart- en vaatziekten;

IHZ = ischemische hartziekten;  IUVD = intra-uteriene vruchtdood; MI = myocard infarct;

NA = niet aangedaan door ziektebeeld; nb = niet bekend; NF = niet fataal; PE = pre-eclampsie;

PIH = pregnancy induced hypertension/ zwangerschapshypertensie; SD = standaard deviatie;

SGA = small for gestational age / groeibeperkt kind; SLE = systemische lupus erythematodes; TE = thrombo-embolie;

VG = voorgeschiedenis; VTE = veneuze thrombo-embolie

Definitie hypertensie: I zelfrapportage; II medicatie gebruik; III systolische bloeddruk ≥140 mmHg;IV diastolische bloeddruk ≥90 mmHg; V  ICD code

Tabel 4.6.3: risico’s op het ontwikkelen van diabetes mellitus (DM)bij vrouwen die eengroeibeperkt kind

hebben gehad ten opzichte van vrouwen die een ongecompliceerde zwangerschap hebben doorgemaakt

Studie

Definitie SGA

N

Gem FU (jr)

Gem lft FU

Definitie DMT

Aantal vrouwen met DM (N)

Gecorrigeerde risico’s (95% CI)

Gecorrigeerd voor

A

NA

A

NA

A

NA

Cohort onderzoeken waarin vrouwen met een groeibeperkt kind zijn vergeleken met vrouwen zonder groeibeperkt kind

Lykke

2012

-2.0 – -3.0

SD

33 366

266 178

14.6

~41 jr

V

331

1892

HR 0.93 (0.83-1.05)

Lft, jaar van bevalling, hypertensieve aandoening

zwangerschap, vroeggeboorte,

abruptio placentae, IUVD

< -3.0 SD

6447

108

HR 1.04 (0.85-1.28)

Onderzoeken met patiënten series waarin vrouwen met een groeibeperkt kind zijn vergeleken met vrouwen zonder groeibeperkt kind

Berends, 2008

≤p5

56

106

9.3

39

39.2

VII

2

0

-

Geen

Afkortingen: A = aangedaan door ziektebeeld;  B = beroerte; BI =  beroerte, ischemisch;

BH = beroerte, hemorragisch; BMI = body mass index;   DM = diabetes mellitus;  DR = dysritmie;

F = fataal; FU = follow-up; GDM = diabetes gravidarum; HT = hypertensie;

CV gebeurtenis = hart- en vaatziekten; IHZ = ischemische hartziekten;  IUVD = intra-uteriene vruchtdood;

MI = myocard infarct; NA = niet aangedaan door ziektebeeld; nb = niet bekend; NF = niet fataal;

PE = pre-eclampsie; PIH = pregnancy induced hypertension/ zwangerschapshypertensie; SD = standaard deviatie;

SGA = small for gestational age / groeibeperkt kind; SLE = systemische lupus erythematodes; 

TE = thrombo-embolie; VG = voorgeschiedenis; VTE = veneuze thrombo-embolie

Definitie DM: I zelfrapportage; II medicatie gebruik; III nuchtere glucose ≥ 7.0 mmol/l;

IV random glucose ≥ 11.1 mmol/l; V  ICD-9 codes; VI WHO criteria; VII = onbekend; VIII medisch dossier

Tabel 4.6.4: risico’s op het ontwikkelen van dyslipidemiebij vrouwen die eengroeibeperkt kind

hebben gehad ten opzichte van vrouwen die een ongecompliceerde zwangerschap hebben doorgemaakt

Studie

Definitie SGA

N

Gem FU (jr)

Gem lft FU (jr)

Definitie dyslipi-demie

Aantal met dyslip

(N)

Gecorrigeerde HR risico’s (95% BI)

Gecorrigeerd voor

A

NA

A

NA

A

NA

Onderzoeken met patiënten series waarin vrouwen met een groeibeperkt kind zijn vergeleken met vrouwen zonder groeibeperkt kind

Berends, 2008

≤p5

56

106

9.3

39

39.2

II

1

1

1.89 (0.12-12.69)

Geen

Catov, 2011

<p10

192

304

8

37.3

36.5

V

7

15

0.98 (0.40-2.54)

Lft, ras, opleiding,

inkomen, BMI, roken

IV

32

42

1.37 (0.79-2.20)

Afkortingen: A = aangedaan door ziektebeeld;  B = beroerte; BI =  beroerte, ischemisch;

BH = beroerte, hemorragisch; BMI = body mass index;   DM = diabetes mellitus; 

DR = dysritmie; F = fataal; FU = follow-up; GDM = diabetes gravidarum; HT = hypertensie;

CV  gebeurtenis = hart- en vaatziekten; IHZ = ischemische hartziekten;  IUVD = intra-uteriene vruchtdood;

MI = myocard infarct; NA = niet aangedaan door ziektebeeld; nb = niet bekend; NF = niet fataal;

PE = pre-eclampsie; PIH = pregnancy induced hypertension/ zwangerschapshypertensie;

SD = standaard deviatie; SGA = small for gestational age / groeibeperkt kind;

SLE = systemische lupus erythematodes;  TE = thrombo-embolie; VG = voorgeschiedenis;

VTE = veneuze thrombo-embolie

Definitie dyslipidemie:I zelfrapportage; II medicatie gebruik; III  cholesterol ≥5.0 mmol/l ;

IV triglyceriden ≥1.7 mmol/l; V HDL ≤0.9 mmol/l; VI totaal cholesterol ≥6.2 mmol/l