Table 1.
Summary of the included studies.
| Author | Geographic Area | Study Design | Included Participants | Assessment of Dietary Habits | Assessment of Adherence to MD | Outcomes | Results |
|---|---|---|---|---|---|---|---|
| Timmermans et al. (2012) [38] |
Netherlands | Prospective population-based cohort study | 3207 mothers with a spontaneously conceived live-born singleton pregnancy | Semi-quantitative FFQ (293 items) self-administered during early pregnancy (GA < 18 weeks) | Logistic regression analysis was used to identify a comparable dietary pattern, which was labeled MD as it was characterized by higher intakes of pasta, rice, vegetable oils, fish, vegetables and alcohol, and lower intakes of meat, potatoes and fatty sauces. All women were categorized into equal tertiles based on their probability score for the diet, namely: low MDA, medium MDA and high MDA. | Fetal growth | Low MDA resulted associated with lower birth weight (difference in grams at birth −72 [95% CI: −110.8 to 33.3]) |
| Chatzi et al. (2012) [39] |
Spain (INMA cohort) and Greece (RHEA cohort) | Prospective population-based cohort study | Spain: 2461 mother-newborn pairs. Greece: 889 mother-newborn pairs | Semi-quantitative FFQ (100 items in IMNA cohort and 250 items in RHEA cohort) administered by trained interviewers during first (IMNA cohort) or mid trimester (RHEA cohort) of pregnancy | Trichopoulou’s score [40] modified for pregnancy | Fetal growth | High MDA was associated with lower risk of delivering a FGR infant (OR 0.5 [95% CI: 0.3–0.9]) in the INMA-Mediterranean cohort. In all cohort high MD adherence increased birth weight in smoking mothers |
| Sauders et al. (2014) [41] |
Guadeloupe (French Caribbean Island) | Prospective mother-child cohort study | 728 pregnant women with a live-born singleton pregnancy without major congenital malformations | Semi-quantitative FFQ (214 items) administered by trained interviewers in the days after delivery | Trichopoulou’s score [40] | Fetal growth and prematurity | No overall associations with FGR. No overall association with prematurity. Decreased risk in overweight and obese woman (adjOR 0.7 [95% CI: 0.6–0.9]) |
| Gomez-Roig et al. (2017) [42] |
Spain | Cross-sectional study | 46 mothers with SGA fetuses 81 mothers with appropriate for gestational age (AGA) fetuses |
Semi-quantitative FFQ (127 items) administered by trained interviewers during the third trimester of pregnancy | Trichopoulou’s score [40] | SGA infants | High MD score was associated with a lower risk of SGA (OR 0.18 [95% CI: 0.74–0.501]) for the third consumer quartile |
| Peraita-Costa et al. (2018) [43] |
Spain | Cross-sectional population-based study | 492 mothers | Semi-quantitative FFQ (16 items) self-administered after delivery | Modified KidMed score [44] | SGA infants | The newborns born to women with low MDA presented a higher risk of being SGA (adjOR 1.68 [95% CI: 1.02–5.46]) when adjusting for parental BMI and multiple gestation, but not when adjusting for all significant possible confounders. |
| Parlapani et al. (2017) [45] |
Greece | Single-center, prospective, observational cohort study | 82 women who delivered preterm singletons at post conceptional age < 34 weeks | Semi-quantitative FFQ (156 items) self-administered immediately before or after delivery | Panagiotakos dietary score [46] | Fetal growth and prematurity-associated complications | Low MD adherence increased the risk of IUGR, low birth weight, bronchopulmonary dysplasia and necrotizing enterocolitis in preterm infants (<34 weeks) |
| Martinez-Galiano et al. (2018) [47] |
Spain | Prospective multicenter matched case-control study (matching criterion: maternal age at delivery) | 518 mothers of singleton SGA infants 518 mothers of singleton infants with normal weight for GA |
Semi-quantitative FFQ (137 items) administered by trained interviewers within 2 days after delivery | PREDIMED score [48], Trichopoulou’s score [40], Panagiotakos’ score [46] | SGA infants | MDA and daily consumption of 5 gr of olive oil was associated to a reduced risk of SGA in newborns (adjOR 0.59 [95% CI: 0.38–0.98]) |
| Assaf-Balut et al. (2017) [49] |
Spain | Prospective randomized controlled intervention trial | 500 mothers allocated to intervention (MD diet supplemented with extra virgin olive oil and pistachios) and 500 allocated to control (standard diet with limited fat intake) | Semi-quantitative FFQ (14 items) administered by trained interviewed during 4 study visits (at first ultrasound visit at 24–28 GA, at 36–38 GA, and at delivery) to evaluate the adherence to the intervention | MDA screener score [50] | SGA infants and prematurity | MD supplemented with extravergin olive oil and pistachios significantly reduced prematurity rate (p 0.023) and SGA (p 0.001) in the intervention group |
| Carmichael et al. (2013) [51] |
United States | Cross-sectional study | 5738 mothers with a singleton pregnancy who delivered non-malformed infants | Semi-quantitative FFQ (58 items) administered by telephone interview 6 weeks—24 months after delivery | Trichopoulou’s score [40] and DQI incorporating pregnancy-specific nutritional recommendations [52] | Prematurity | No association |
| Mikkelse et al. (2008) [53] |
Denmark | Prospective cohort study | 35657 pregnant women with a live-born singleton pregnancy | Semi-quantitative FFQ (360 items) self-administered at mid-pregnancy (week 25) by mail | Khoury’s score [54] | Prematurity | High MDA reduced the risk of early preterm birth (adjOR 0.28 [95% CI: 0.11–0.76]). No associations with late preterm delivery. |
| Haugen et al. (2008) [55] |
Norway | Prospective cohort study | 26563 pregnant women with a live-born singleton pregnancy | Semi-quantitative FFQ (255 items) self-administered at week 18–22 of pregnancy | Khoury’s score [54] | Prematurity | No association |
| Smith et al. (2015) [56] |
United Kingdom | Population-based cohort study | 922 mothers with singleton late and moderate preterm (LMPT) births 965 mothers with singleton term births |
Maternal interview shortly after delivery | MDA on the basis of the presence of at least 1 of the following major criteria: five portions of fruit and vegetables every day; fish more than twice a week; meat no more than twice a week; max two cups of coffee/d. | Late and moderately preterm (LMPT) birth | Higher risk of delivering LMPT in not adherent women (RR 1.81 [95% CI: 1.04–3.14]) |
| Vujkovic et al. (2009) [57] |
Netherlands | Retrospective multicenter case-control study | 50 mothers of children with spina bifida 81 control mothers |
Semi-quantitative FFQ (200 items) administered 14 months after delivery and individually checked for consistency at the hospital or by telephone by the researcher. | Principal component factor analysis (PCA) and reduce rank regression (RRR) were used to identify a comparable dietary pattern, which was labeled MD as it was characterized by high intake of vegetables, fruits, vegetable oils, legumes, fish, alcohol and cereal products and low intakes of potatoes and sweets. | NTDs | Low MDA according to both PCA and RRR, was associated with an increased risk of spina bifida (OR 2.7 [95% CI: 1.2–6.1] and OR 3.5 [95% CI: 1.5–7.9], respectively) |
| Carmicheal et al. (2012) [58] |
United States | Retrospective multicenter case-control study | 936 mothers of children with NTDs 2475 mothers of children with orofacial clefts 6147 control mothers |
Semi-quantitative FFQ (58 items) administered by telephone interviews 6 weeks–24 months after delivery | Trichopoulou’s score [40] and DQI [52] incorporating pregnancy-specific nutritional recommendations | NTDs and orofacial clefts | High Trichopoulou score and DQI score were protective for NTDs, with a stronger association observed for anencephaly (adjOR 0.64 [95% CI: 0.45–0.92] and 0.49 [95% CI: 0.31–0.75], respectively) |
| Botto et al. (2016) [59] |
USA | Population based, multicenter case-control study | 9885 case mothers 9468 control mothers |
Semi-quantitative FFQ (58 items) administered by telephone interviews 6 weeks–24 months after delivery | Trichopoulou’s score [40] and the DQI [52] incorporating pregnancy-specific nutritional recommendations | Congenital Heart Defects | High Trichopoulou’s score was protective only for perimembranous ventricular septal defects (14%, OR 0.86 [95% CI: 0.69–1.07]). High DQI was protective for tetralogy of Fallot (OR 0.63 [95% CI: 0.49–0.80]), conotruncal defects (OR 0.76 [95% CI: 0.64–0.91]), atrial septal defects (OR 0.77 [95% CI: 0.63–0.94]) and for all septal defects (OR 0.86 [95% CI: 0.75–1.00]). |
| Feldkamp et al. (2014) [60] |
USA | Population based, multicenter case-control study | 1125 gastroschisis cases 9483 controls |
58-item FFQ (58 items) administered by a computerized-assisted telephone interview (CATI) to case and control mothers 6wk to 24 months delivery |
Trichopoulou’s score [40] and the DQI [52] incorporating pregnancy-specific nutritional recommendations | Gastroschisis | High Trichopoulou’s score (quartile 2, adjOR0.62 [95% CI: 0.33–1.16]; quartile 3, adjOR0.51 [95% CI: 0.28–0.94]; quartile 4, adjOR0.50 [95% CI: 0.28, 0.90]) and DQI score (quartile 2, adjOR 0.58 [95% CI: 0.40–0.86]; quartile 3, adjOR 0.52 [95% CI: 0.36–0.79]; quartile 4, adjOR 0.48 [95% CI: 0.32–0.76]) were protective for gastroschisis. |
| Chatzi et al. (2008) [61] |
Spain | Cohort study | 460 children | Semi-quantitative FFQ (42 items) referred to the pregnancy and administered to mothers 3 months after delivery by a face-to-face interview. Semi-quantitative FFQ (96 items) administered to the parents of the children at 6.5 year of age by an interviewer | Trichopoulou’s score [40] | Wheeze, atopic wheeze and atopy at 6.5 years | High MDS in mothers was protective for persistent wheeze (adjOR 0.22 [95% CI:0.08–0.58]), atopic wheeze (adjOR0.30 [95% CI:0.10–0.90]), and atopy (adjOR 0.55 [95% CI: 0.31–0.97]) in children at 6,5 years |
| De Batlle et al. (2008) [62] |
Mexico | Cross-sectional study | 1476 children | Semi-quantitative FFQ (70 items) referred to the pregnancy and self-administered at the children age of 6–7 years | Trichopoulou’s score [40] | Asthma, Wheezing, rhinitis, sneezing, itchy-watery eyes at 6-7 years | High MDS was protective for current sneezing (OR 0.71 [95% CI: 0.53–0.97]). |
| Castro-Rodriguez et al. (2010) [63] |
Spain | Cohort study | 1409 infants | Semi-quantitative FFQ (11 items) referred to the pregnancy and self-administered at the children’s aged of 15–18 months | MDS modified from Psaltopoulou [64] | Wheeze at 12 months | MD (p 0.036) and olive oil (p 0.002) were associated with less wheezing. Only olive oil intake remained inversely associated with wheezing (adjOR 0.57 [95% CI: 0.4–0.9]) |
| Chatzi et al. (2013) [65] |
Spain (INMA cohort) and Greece (RHEA cohort) | Cohort study | Spain: 1771 mother-newborn pairs. Greece: 745 mother-newborn pairs |
Semi-quantitative FFQ (100 items in IMNA cohort and 250 items in RHEA cohort) administered by trained interviewers at mean 13.8 weeks of GA (IMNA cohort) or 14.6 weeks of GA (RHEA cohort) | Trichopoulou’s score [40] modified for pregnancy considering dairy food protective and not including in the score alcohol consumption. | Wheeze and eczema at 12 months | No associations between MD score and wheeze and eczema |
| Alvarez-Zallo et al. (2018) [66] |
Spain | Cohort study | 1087 mother-infant pairs | Semi-quantitative FFQ (11-items) referred to the pregnancy and self-administered at the children aged 12–15 months | MDS modified from Psaltopoulou [64] | Wheeze and eczema at 12–15 months | No associations between MD score and wheezing, recurrent wheezing and eczema |
| Lange et al. (2010) [67] |
United States | Cohort study | 1376 mother-infant pairs | Semi-quantitative FFQ (166 items) self-administered at the first and second trimesters visits | MD score modified from Trichopoulou [40], Alternate Healthy Eating Index modified for pregnancy [68] and PCA to look at Western and Prudent diets | Wheeze, asthma and atopy at 3 years | No associations between dietary patterns and asthma, atopy or wheezing |
| Castro-Rodriguez et al. (2016) [69] |
Spain | Cohort study | 1000 mother-newborn pairs | Semi-quantitative FFQ (11 items) regarding the consumption of foods during pregnancy self-administered at the time point of 1.5 years of children’s life. Semi-quantitative FFQ (11 items) regarding the consumption of food by the child self-administered at the time point of 4 years of life | MDS modified from Psaltopoulou [64] | Wheeze, dermatitis and allergic rhinitis at 4 years | No associations between MD score and wheezing, rhinitis and dermatitis |
| Gesteiro et al. (2012) [70] |
Spain | Cross sectional study | 35 women | 169 items FFQ conducted by a trained dietician 3–5 after delivery | Healthy eating index (HEI) adapted for the Spanish population [71] and by a modified MDA scores used in the PREDIMED study [72] | Various insulin sensitivity/resistance biomarkers at birth | Low HEI- or low MDA-score diet delivered infants with high insulinaemia (p 0.048 or p 0.017, respectively), HOMA-IR (p 0.031 or p 0.049, respectively) and glycaemia (p 0.018 or p 0.048, respectively). The relative risk (RR) of high-neonatal glycaemia and insulinaemia were 7.6 (p 0.008) and 6.7 (p 0.017) for low vs. high HEI-score groups. High HOMA-IR and high glucose RR were, respectively, 3.4 (p 0.043) and 3.9 (p 0.016) in neonates from the <7 MDA- vs. >7 MDA-score group. |
| Chatzi et al. (2017) [73] |
USA (Project Viva cohort) and Greece (RHEA cohort) | Prospective mother–child cohort study | 997 mother–child pairs from Project Viva and 569 pairs from the RHEA study | In Project Viva, mothers reported their diet since the time of their last menstrual period at study enrolment (median 9.9 weeks gestation) using a validated semi-quantitative FFQ. RHEA participants completed a validated FFQ at mean 14.6 weeks gestation. | Trichopoulou’s score [40] | BMI z-score, waist circumference, skin-fold thickness, systolic and diastolic blood pressure | In the pooled analysis, for each 3-point increment in the MDS, offspring BMI z-score was lower by 0.14 units (95% CI: −0.15 to −0.13), waist circumference by 0.39cm (95% CI: −0.64 to −0.14), the sum of skin-fold thicknesses by 0.63mm (95% CI: 0.98 to −0.28), systolic blood pressure by −1.03 mmHg (95% CI: −1.65 to −0.42) and diastolic blood pressure by −0.57 mmHg (95% CI: −0.98 to −0.16). |
| Fernández-Barrés et al. (2016) [74] |
Spain | Population based cohort study | 1827 pairs of mother and children | Validated 101 items FFQ conducted from first to third trimester | RelativeMediterranean diet score (rMED) [75] | BMI and waist circumference | A significant association between higher adherence to MD and lower waist circumference (−0.62 cm [95% CI: −1.1 to −0.14]). |
| Gesteiro et al. (2015) [76] |
Spain | Cross sectional study | 35 women | Complete 169 items FFQ guided by a trained dietician conducted at first trimester | Modified MDA scores used in the PREDIMED study [72] | Cord blood lipoprotein and homocysteine concentrations | Mothers at the low MDA-score delivered neonates with high cord blood LDL-c (p 0.049), Apo B (p 0.040), homocysteine (p 0.026) and Apo A1/Apo B ratio (p 0.024). |
| Mantzoros et al. (2010) [77] |
USA | Prospective cohort study | 780 women | Slightly modified semi-quantitative FFQ at both the first and second trimester | Trichopoulou’s score [40] | Cord blood leptin and adiponectin concentrations | Closer adherence to a Mediterranean pattern diet during pregnancy was not associated with cord blood leptin (p 0.38) or adiponectin (p 0.93) |
| Gonzalez-Nahm et al. (2017) [78] |
USA | Cohort study | 390 women whose infants had DNA methylation data available from cord blood leukocytes | 150 items FFQ at preconception or at first trimester | Modified Trichopoulou’s score [40] | Methylation at the MEG3-IG region | Infants of mothers with a low adherence to a Mediterranean diet had a greater odd of hypo-methylation at the MEG3-IG differentially methylated region (OR 2.80 [95% CI: 1.35−5.82]) |
adjOR: adjusted odds ratio; BMI: body mass index; CI: confidence interval; GA: gestational age; FFQ: food frequency questionnaire; MEG3-IG: maternally expressed gene 3 - intergenic region; MD: Mediterranean Diet; MDA: Mediterranean Diet adherence; NTDs: neural tube defects; OR odds ratio; PTD: preterm delivery; RR: relative risk; SGA: small for gestational age; LMPT: Late and moderately preterm; HOMA-IR: homeostatic model assessment for insulin resistance.